Visual feedback manipulation in virtual reality to influence pain-free range of motion. Are people with non-specific neck pain who are fearful of movement more susceptible?

Maaike Kragting; Lennard Voogt; Michel W Coppieters; Annelies L Pool-Goudzwaard

doi:10.1371/journal.pone.0287907

. 2023 Jul 5;18(7):e0287907. doi: 10.1371/journal.pone.0287907

Visual feedback manipulation in virtual reality to influence pain-free range of motion. Are people with non-specific neck pain who are fearful of movement more susceptible?

Maaike Kragting ^1,², Lennard Voogt ^1,³, Michel W Coppieters ^2,^4,^5,^*, Annelies L Pool-Goudzwaard ^2,⁶

Editor: Mariella Pazzaglia⁷

PMCID: PMC10321611 PMID: 37406021

Abstract

Background

Movement-evoked pain may have a protective or learned component, influenced by visual cues which suggest that the person is moving towards a position that may be perceived as threatening. We investigated whether visual feedback manipulation in virtual reality (VR) had a different effect on cervical pain-free range of motion (ROM) in people with fear of movement.

Method

In this cross-sectional study, seventy-five people with non-specific neck pain (i.e., neck pain without a specific underlying pathology) rotated their head until the onset of pain, while wearing a VR-headset. Visual feedback about the amount of movement was equal, 30% smaller or 30% larger than their actual rotation. ROM was measured using the VR-headset sensors. The effect of VR manipulation in fearful (N = 19 using the Tampa Scale for Kinesiophobia (TSK) and N = 18 using the Fear Avoidance Beliefs Questionnaire-physical activity (FABQ_pa)) and non-fearful (N = 46; non-fearful on both scales) people was compared using mixed-design ANOVAs.

Results

Fear of movement, influenced the effect of visual feedback manipulation on cervical pain-free ROM (TSK: p = 0.036, ղ_p² = 0.060; FABQ_pa: p = 0.020, ղ_p² = 0.077); a greater amplitude of pain-free movement was found when visual feedback reduced the perceived rotation angle compared to the control condition (TSK: p = 0.090, ղ_p² = 0.104; FABQ_pa: p = 0.030, ղ_p² = 0.073). Independent of the presence of fear, visual feedback manipulation reduced the cervical pain-free ROM in the overstated condition (TSK: p< 0.001, ղ_p² = 0.195; FABQ_pa: p<0.001, ղ_p² = 0.329).

Discussion

Cervical pain-free ROM can be influenced by visual perception of the amount of rotation and people with fear of movement seem to be more susceptible to this effect. Further research in people with moderate/severe fear is needed to determine whether manipulating visual feedback may have clinical applicability to make patients aware that ROM may be influenced more by fear than tissue pathology.

Introduction

In people with non-specific neck pain (i.e., neck pain without a specific underlying pathology [1]), movement-evoked pain may be a protective or learned response. This response may be influenced by visual cues which suggest that a patient is moving their head towards a position that may be perceived as threatening [2]. Visual cues previously accompanied by pain during certain cervical movements may be stored in memory and may become associated with the perception of pain [3–5]. Results from a previous study [2] support this hypothesis, by showing that cervical pain-free range of motion can be influenced in people with non-specific neck pain by altering visual feedback regarding the amount of rotation in a virtual reality (VR) environment. This finding is interesting, as the use of VR may facilitate people with neck pain to learn a new association (i.e., a previously painful movement becomes pain-free), which can be of therapeutic value. However, a large variability between participants existed regarding the size of the effect of visual feedback manipulation on changes in pain-free range of motion [6]. Another study using a similar methodology [2] did not find an effect of visual feedback manipulation on cervical pain-free range of motion in a larger group of people with non-specific neck pain [7]). Hence, further research into the role of visual stimuli on pain perception is needed.

A possible explanation for the different results between studies regarding the role of visual stimuli on pain perception might be that pain is a conditioned response in only a subgroup of patients. Following the assumption that visual cues serve as warning signals associated with pain that prevent people from moving beyond a certain, learned, movement range [2, 8, 9], it is hypothesized that individuals who report high levels of fear of movement may be more prone to visual feedback manipulation than others. The underlying assumption is that individuals who are not fearful of movement may unlearn the association made between movement and pain, allowing pain to be reduced. In contrast, in individuals who are fearful of movement these maladaptive patterns of learning may continue to exist because of avoidance behaviour [8, 10–14].

The aim of the current study was to evaluate whether the effect of visual feedback manipulation was different in people with non-specific neck pain who are fearful of movement, compared to people with non-specific neck pain who are not fearful of movement.

Methods and materials

Participants

People with non-specific neck pain were recruited between April and December 2018 from 12 primary care physiotherapy clinics in The Netherlands, using the convenience sample method. The physiotherapist performed the initial screening. Inclusion criteria were: 1) neck pain Grade I and II (i.e., Grade I: neck pain with no signs of major pathology and no or little interference with daily activities; Grade II: neck pain with no signs of major pathology, but with interference with daily activities [15]) that was provoked and/or aggravated by cervical rotation, 2) aged between 18–65 and 3) being able to read and understand Dutch. People were excluded if they had neck pain with neurological signs (i.e., neck pain Grade III), neck pain with signs of serious pathology (i.e., neck pain Grade IV) [15] or if their vision was impaired (e.g., people who had poor vision when not wearing their glasses as they could not be worn in the VR condition. The use of contact lenses was not a problem).

A sample size calculation was carried out a priori using an ANOVA repeated-measures within-between interaction in G-power 3.1 [16]. Because of the mixed design that was used in this study, we expected a smaller effect than the (within) effect of altered visual feedback on cervical pain-free range of motion as revealed in a previous study (η_p² = 0.29) [2]. Therefore, we devided this effect by two, which was an arbitrary choice. Based on an expected effect size of η_p² = 0.145 (i.e., 0.29/2), a significance level of α<0.05, a power of 0.8, 2 groups, 3 measurements and assuming a 75% correlation among repeated-measures, the minimum required number of participants was 40, i.e., 20 per group.

The Scientific and Ethical Review Board (VCWE) of the Vrije Universiteit Amsterdam approved the study (VCWE-2016-218R1). Prior to study participation, all participants received an information letter and provided written consent. The STROBE reporting guideline for cross-sectional observational studies was followed [17].

Procedure

Participants completed a digital questionnaire (Qualtrics, Provo, UT) to collect personal and neck pain related information regarding age, sex, the duration and onset of their neck pain (gradual or sudden, and if sudden, history of trauma), kinesiophobia, fear of physical activity, neck pain intensity and disability (see ‘Measurements’ section below for further specifications). Within a week after completion of the questionnaire, the VR-experiment was performed at one of the participating physiotherapy practices, to evaluate the effect of visual feedback manipulation on cervical pain-free range of motion. Motion sickness is a common side effect in VR [18], especially in people with neck pain [19], and a possible barrier when considering implementing VR in clinical practice. Therefore, motion sickness was evaluated following the VR-experiment using the short version of the Misery Scale (sMISC).

Measurements

Fear

Fear is a complex multidimensional phenomenon containing several distinct, but closely related constructs, such as fear of movement/reinjury, kinesiophobia, fear of pain and fear avoidance [20]. Congruent with our hypothesis and taking into account the multidimensionality of the construct fear, we used two different questionnaires to create the fear of movement subgroups (i.e., people with either kinesiophobia or fear of physical activity, or both), being the (1) Tampa Scale of Kinesiophobia (TSK) (construct: kinesiophobia) and (2) Fear Avoidance Beliefs Questionnaire, physical activity subscale (FABQ_pa)) (construct: fear of physical activity). The TSK and the FABQ_pa are validated self-reported instruments recommended to assess fear of movement [20, 21]. Both scales use standardised cut-off points to distinghuish people with and without fear of movement.

The TSK consists of 17 items, each scored on a 4-point Likert scale [22, 23]. The total score ranges from 17 to 68, with a score >37 being regarded as indicative for kinesiophobia [23]. The Dutch version of the TSK is reliable and has been validated in people with low back pain and fibromyalgia [24], but has not yet been validated for neck pain. The psychometric properties of the TSK in people with neck pain have been studied in several countries in various neck pain populations. Reliability and validity are moderate to good [25–27].

The FABQ_pa contains 4 items regarding beliefs about how physical activity affects pain, each scored on a 6-point Likert scale [28]. A score >14 is indicative for fear of physical activity [29, 30]. The internal consistency, test-retest reliability and validity of the FABQ in people with neck pain is acceptable [25, 26, 31].

Pain and disability

Pain intensity was measured on a 11-point scale using the Numeric Pain Rating Scale (NPRS), which is simple and valid tool [32]. The Neck Disability Index (NDI) was used to assess the level of disability in people with neck pain. It is a reliable and responsive tool which consists of 10 items with six response categories (range 0–5, total score range 0–50), with higher scores representing higher disability [33–35].

Motion sickness

The Misery Scale (short version) (sMISC) was used to assess feelings of misery [36–38]. This scale is easy to administer and correlates strongly with the more extensively validated Simulator Sickness Questionnaire [36, 39]. The sMISC is scored on a 6-point scale in which 0 = No symptoms, 1 = Mild symptoms, but no nausea, 2 = Severe symptom, but no nausea, 3 = Mild nausea, 4 = Severe nausea and 5 = Vomiting.

Visual feedback manipulation and cervical pain-free range of motion

During the VR-experiment participants sat on a chair, wearing a fixation belt to limit upper trunk movement (see Fig 1). They wore a VR-headset (Oculus Rift head-mounted display; Oculus VR, Irvine, CA, United States), and noise cancelling headphones to reduce ambient noise and to distract them from the research setting by playing background music (nature sounds), which was held constant between the conditions. Standardised instructions on what tasks to perform were delivered via the headphones using pre-recorded audio files.

Participants faced forward and were asked to rotate their head slowly to the left until the onset of pain, then to the right until the onset of pain, and then back to the midline, while submerged in a VR environment. This rotation was repeated six times in three different conditions. In two conditions the illusion was created of moving 30% less (understated visual feedback) or moving 30% more (overstated visual feedback) than the actual physical rotation. A condition with accurate visual feedback was considered the control condition. A total of eighteen rotations were performed. To create an illusion of a smaller or larger movement than the actual movement, a technique called ‘redirected walking’ was used [40]. This technique tracks the actual head rotation and transforms it to the VR environment in an overstated or understated form. The rotation gain (i.e., the factor by which actual rotation translates to the visual rotation as shown by the VR headset (Gain_rot = Rot_virtual/Rot_real) (2), was set at 0.7 (understated condition), 1.0 (control condition) and 1.3 (overstated condition). The choice for the 0.7 and 1.3 gains was based on the results of a pilot study that aimed to determine the largest rotation gains that were more likely to be judged as ‘not manipulated’ than ‘manipulated’. For more detailed information on this pilot study, please see S1 Appendix.

There was a two-minute rest period after six repetitions to minimise motion sickness and to assess pain intensity during the experiment, as fluctuations in pain may influence the results. During the rest period participants kept the VR-headset on and had their eyes closed.

The total range of motion (i.e., from maximal left rotation to maximal right rotation) for each repetition was measured in degrees using the sensors of the VR-headset which was connected to a computer running Windows 10 (Microsoft Corporation, Redmond, WA, USA). This method of data acquisition and its validation has been described in detail in a previous publication [7]. Subsequently, the average range of motion of six repetitions was calculated for each gain condition (i.e., absolute data). To account for differences in the overall neck range of motion between subjects, for each participant, the data from the overstated and understated condition were transformed to a proportion of the mean range of rotation in the control condition (i.e., relative data). Between subject differences (especially between people with and without fear of movement) were anticipated [41, 42].

The order in which the gain conditions were offered (increasing gains (i.e., 0.7; 1.0; 1.3) or decreasing gains (i.e., 1.3; 1.0; 0.7)) was randomised and counterbalanced across participants. We used block randomization to balance the distribution between increasing and decreasing gains throughout the study. Participants were blinded for the sequence of each condition. The experimenter was blinded for the presence of fear. For each gain condition, six different environments (loft, workman’s shed, living room, dungeon, undulating landscape and a forest) (Unity 5.3.1, Unity Technologies, San Francisco, CA, United States) were used to prevent the participants from recalling their previous position. Hence, one environment was used per repetition for each condition. We chose to use the same types of (indoor and outdoor) environments as in a previous study [2] (see S1 Fig).

At the end of the experiment, participants were asked whether they had noticed any differences between the multiple rotations to assess whether they were naïve to the gain change.

Statistical analyses

To examine whether the effect of visual feedback manipulation on cervical pain-free range of motion was different between people with fear and people without fear, two separate analyses were performed (one for TSK, and one for FABQ_pa), using the relative data (reported in the main article) and the absolute data (reported in Table 2 and the S2 Appendix). For both the relative and absolute data, people were classified separately as being fearful according to the TSK and FABQ_pa scores (TSK: fearful for movement (kinesiophobia), i.e., TSK>37; FABQ_pa: fear of physical activity, i.e., FABQ_pa>14), or non-fearful for movement (i.e., negative on both scales; i.e., TSK≤37 & FABQ_pa≤14). In both analyses, a General Linear Model (GLM), repeated-measures mixed-design ANOVA (with the within-variable gain (3) and between-variable fear (2)) was performed [43]. The results were presented using exact p-values, the effect estimate and its 95% confidence interval. Partial η² was calculated to determine the effect size. An effect size between 0.01 and 0.059 was considered small, between 0.06 and 0.138 medium and ≥0.139 was considered large [44].

The assumption of normality was assessed by visual inspection of the histograms and Q-Q plots. The assumption of equality of variances between the two subgroups (fear/no fear) per analysis on cervical pain-free range of motion in the understated and overstated gain conditions was checked using Levene’s test for homogeneity of variance. The assumption of sphericity was checked according to Girden [45]. When appropriate, the mixed-design ANOVA was followed-up with simple contrasts to identify whether specific differences occurred between the three gain conditions.

Pain ratings were compared among conditions using a repeated-measures ANOVA or, in case of violations of the normality assumptions, a Friedman’s ANOVA [46, 47]. For the ordinal sMISC scores, frequencies and percentages were reported. All statistical analyses were conducted using SPSS (IBM Corp. (2020). IBM SPSS Statistics for Windows, Version 27.0. Armonk, NY).

Results

Participant characteristics and comparability between groups

Seventy-five people with neck pain volunteered for the study (51 females; mean (SD) age: 44.3 (14.5) years)). One additional participant was unable to complete the experiment due to nausea and was excluded from the study. We decided to recruit more than the 40 participants that were required based on the sample size calculation, because the subgroups (fear/no fear) were not equally distributed. We enrolled participants until we had sufficient people with fear of movement.

Using the TSK score, 19 participants had kinesiophobia. Using the FABQ_pa score, 18 participants had fear of physical activity. Forty-six participants had no form of fear of movement (TSK≤37 & FABQ_pa≤14). The TSK score was missing for one participant and the FABQ_pa score was missing for two participants. These participants were excluded from this analysis. In both analyses, there were no differences between the fearful and non-fearful group in age and duration of the neck pain, but the fearful group felt more disabled, scored higher on pain intensity and was more limited in the cervical pain-free range of rotation. Table 1 provides an overview of the participant characteristics per group including the results from the comparisons between subgroups.

Table 1. Participant characteristics and comparisons between groups.

Variables	Total N = 75	Subgroups			Mean differences between the No fear of movement and Kinesiophobia subgroups (t-test/MannW)	Mean differences between the No fear of movement and Fear of physical activity subgroups (t-test/MannW)
Variables	Total N = 75	No fear of movement (TSK≤37 & FABQ_pa ≤14) N = 46^a ^b	Kinesio phobia (TSK>37) N = 19^a	Fear of physical activity (FABQ_pa >14) N = 18^b
Women (N (%))	51 (68%)	33 (72%)	11 (58%)	11 (61%)
Trauma (car-accident or fall) in history	23 (31%)	12 (26%)	9 (47%)	6 (33%)
Stage of disorder	N = 71^c	N = 44	N = 19	N = 17
Acute (0–3 weeks)	4 (6%)	2 (5%)	1 (5%)	2 (12%)
Subacute (3 weeks-3 months)	16 (22%)	10 (23%)	4 (21%)	4 (24%)
Chronic (>3–24 months)	27 (38%)	16 (36%)	8 (42%)	5 (29%)
Long-lasting chronic (>24 months)	24 (34%)	16 (36%)	6 (32%)	6 (35%)
Age (in years) (Mean (SD))	44.3(14.5)	45.4 (13.8)	46.8 (14.3)	45.7 (16.0)	t₍₆₃₎ = -0.381, p = 0.704	t₍₆₂₎ = -0.068, p = 0.946
Duration of neck pain (in months) ^c	12 (2.5–72)	13.5 (2.6–102)	12 (3–60)	8 (2.3–42)	^†U = 378.00, z = -0.60, p = 0.549	^†U = 320.00, z = -0.87, p = 0.385
Pain intensity (0–10 NPRS)
Average last week (Mean (SD))	5.0 (2.1)	4.2 (2.0)	6.6 (1.4)	6.2 (1.8)	t₍₆₃₎ = -4.644 p< 0.001	t₍₆₂₎ = -3.692 p< 0.001
Maximum last week (Mdn (25–75%))	7.0 (5.0–8.0)	6.0 (3.8–8.0)	8.0 (7.0–9.0)	8.0 (7.0–9.0)	^†U = 129.00, z = -4.45 p< 0.001	^†U = 167.50, z = -3.72 p< 0.001
Disability (0–50 NDI) (Mdn 25–75%))	13 (7.0–19.0)	9.5 (6.0–14.0)	19 (7.0–26.0)	17.5 (12.8–24.5)	^†U = 129.00, z = -4.45, p< 0.001	^†U = 185.00, z = -3.43, p = 0.001
Pain-free Cervical Range of Motion ^d (degrees (SD))	120.9 (31.4)	128.5 (24.9)	96.5 (32.4)	106.9 (38.4)	t₍₆₃₎ = 4,302 p< 0.001	t_(22,8) = 2.211 p = 0.037
Kinesiophobia (TSK) (Mean (SD))	33.5 (7.0)	29.7 (4.8)	42.2 (4.2)	39.6 (5.7)	t₍₆₃₎ = -12.493, p< 0.001	t₍₆₂₎ = -7.077, p< 0.001
Fear of physical activity (FABQ _pa ) (Mean (SD))	10.2 (5.0)	7.6 (4.0)	14.3 (3.8)	16.4 (1.7)	t₍₆₃₎ = -6.211, p< 0.001	^†U = 0.00, z = -6.20, p< 0.001

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^a For one participant, the Tampa score was missing. Therefore, this participant was not included in one of the subgroups.

^b For two participants, the FABQ_pa score was missing. Therefore, these participants were not included in one of the subgroups.

^c For four participants, the duration of the neck pain was missing.

^d For the pain-free Cervical Range of Motion the mean scores in the control condition are used.

N: number; SD: standard deviation; Mdn: Median; NDI: Neck Disability Index; NPRS: Numeric Pain Rating Scale; TSK: Tampa Scale for Kinesiophobia; FABQ_pa: Fear Avoidance Beliefs Questionnaire—physical activity; t-test/MannW: Mean difference according to a (parametric) independent Samples T-Test, or a

^†(non-parametric) Mann-Whitney U test.

The differences in absolute range of motion between the groups were large. The mean (SD) cervical pain-free range of rotation in the control condition in people with kinesiophobia (TSK) was 96.5 (32.4) degrees, in people with fear of physical activity 106.9 (38.4) degrees and in the ‘no fear’ group 128.5 (24.9) degrees (See Tables 1 and 2 for further specification of absolute range of motion differences between the groups). As this could influence the change induced by visual manipulation as a function of their total cervical ROM, in further analyses, we took into account the relative change in range of motion.

Table 2. Influence of visual feedback manipulation on cervical pain-free range of motion.

Gain condition	Total range of motion (degrees) (mean [95%CI])
	All participants (N = 75)	No fear of movement (TSK≤37 & FABQ_pa≤14) (N = 46^^/^*)	Kinesiophobia (TSK>37) N = 19^*	Fear of physical activity (FABQ_pa>14) N = 18^**
Relative data ¹
0.7 gain	1.008 [0.991, 1.025]	0.993 [0.978, 1.009]	1.043 [0.996, 1.090]	1.036 [0.985, 1.088]
1.0 gain	1.0 [1.0, 1.0]	1.0 [1.0, 1.0]	1.0 [1.0, 1.0]	1.0 [1.0, 1.0]
1.3 gain	0.964 [0.948, 0.981]	0.969 [0.951, 0.987]	0.955 [0.910, 1.000]	0.935 [0.901, 0.969]
Absolute data ²
0.7 gain	120.8 [114.0, 127.5]	127.3 [120.1, 134.4]	99.5 [84.4, 114.6]	108.7 [91.0, 126.4]
1.0 gain	120.9 [113.7, 128.1]	128.5 [121.1, 135.9]	96.5 [80.8, 112.1]	106.9 [87.8, 126.0]
1.3 gain	117.0 [109.5, 124.4]	124.7 [116.9, 132.5]	92.3 [76.6, 107.9]	101.2 [81.6, 120.8]

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¹ Relative data: a proportion of the mean cervical range of rotation in the control condition.

²Absolute data: the total cervical range of motion (i.e., the sum of left and right rotation) in degrees

* For one participant, data regarding the Tampa score was missing. Therefore, this participant was not included in one of the subgroups.

**For two participants, the FABQ_pa score was missing. Therefore, these participants were not included in one of the subgroups.

N: number; 95%CI: 95% Confidence Intervals [lower bound, upper bound]

Statistical assumptions

Based on visual inspection of the Q-Q plots and the histograms, the relative data were considered sufficiently normally distributed. For both analyses (using the TSK score and the FABQ_pa score), Levene’s test revealed that there were no violations of the assumption of homogeneity of variance between the gain conditions. Sphericity was violated for both analyses and the Greenhouse-Geisser EPSILON was <0.75, therefore the Greenhouse-Geisser correction was used in both analyses [46].

Effect of fear and visual feedback manipulation on cervical pain-free range of motion

Using the relative data, the ANOVA revealed an interaction effect between fear of movement (as determined by the TSK and the FABQ_pa subscale) and visual feedback manipulation on cervical pain-free range of motion with a medium effect size (TSK: p = 0.036, ղ_p² = 0.060; FABQ_pa; p = 0.020, ղ_p² = 0.077). This indicates that cervical pain-free range of motion when the visual feedback was manipulated depended on the presence of fear of movement (see Fig 2A & 2B and Table 2). Contrasts revealed that the cervical pain-free range of motion in people with fear was larger in the understated condition, with a medium effect size, compared to the control condition, while not in people without fear of movement (TSK: p = 0.009, ղ_p² = 0.104; FABQ_pa: p = 0.030, ղ_p² = 0.073). In the overstated condition compared to the control condition, the difference in the cervical pain-free range of motion between people with and without fear was small (TSK: p = 0.491, ղ_p² = 0.008; FABQ_pa; p = 0.057, ղ_p² = 0.057). More specifically, in people with fear of movement pain-free range of motion increased by 4.3% (95%CI: -0.4%, 9.0%) (when classified on TSK scores) and by 3.6% (95%CI:-1.5, 8.8%) (when classified on FABQ_pa scores) in the understated condition compared to the control condition, and decreased by -4.5% (95%CI: -9.0%, 0.0%) (TSK) and -6.5% (95%CI:-9.9%, -3.1%) (FABQ_pa) in the overstated condition compared to the control condition. In people without fear, the effect of visual feedback manipulation was only present in the overstated condition: pain-free range of motion decreased by -3.1% (95%CI: -4.9%, 1.3%) in the overstated condition compared to the control condition. The overall effect of the manipulation (i.e., the difference in cervical pain-free range of motion between the understated and the overstated condition) in the kinesiophobia group was 8.8% (95%CI: 8.6%, 9.0%), and 10.1% (95%CI: 8.4%, 11.9%) in the fear of physical activity subgroup, versus 2.4% (95%CI: 2.2%, 2.7%] in the no-fear group.

Fig 2 — Effect of visual feedback manipulation on cervical pain-free range of motion in people without fear of movement (Tampa≤37 & FABQ_pa≤14) versus people with kinesiophobia (Tampa>37) (A) and versus people with fear of physical activity (FABQ_pa>14) (B). Please note that the relative change in range of motion is used (i.e. a proportion of the mean range of rotation in the control condition). The error bars represent the 95% confidence intervals.

Further analyses showed a main effect of gain (i.e., independent of the presence of fear) on cervical pain-free range of motion with a large effect size (TSK: p<0.001, ղ_p² = 0.158; FABQ_pa: p<0.001, ղ_p² = 0.195). Within subjects contrasts showed that this effect of gain was large for the overstated condition compared to the control condition (TSK: p< 0.001, ղ_p² = 0.195; FABQ_pa: p<0.001, ղ_p² = 0.329), while small for the understated condition versus the control condition (TSK: p = 0.055, ղ_p² = 0.057; FABQ_pa: p = 0.137, ղ_p² = 0.035). For the results of the analyses using the absolute data, see Table 2, S3 Fig in S2 Appendix.

Exploratory analysis

The results showed that the mean TSK and FABQ_pa scores in the ‘fear groups’ were close to the cut-off points to be considered fearful. To increase the contrast between the ‘no fear’ and ‘fear’ group, we decided to perform an exploratory analysis in which people who were negative on both scales (N = 46; TSK≤37 & FABQ_pa≤14) were compared to participants who scored positive on both scales (N = 10; TSK>37 & FABQ_pa>14). The effect size regarding the interaction effect between fear of movement and visual feedback manipulation on cervical pain-free range of motion was then twice as large (p = 0.007, ղ_p² = 0.112). In people with fear of movement cervical range of motion increased by 5.2% (95%CI: -2.1%, 12.4%) in the understated condition and decreased by -7.5% (95%CI:-12.6%, -2.4%) in the overstated condition. The overall effect of the manipulation (i.e., the difference in cervical pain-free range of motion between the understated and the overstated condition) in the fear group was 12.7% (95%CI: 10.5%, 14.8%). The results of the exploratory analysis are included in S1 Table.

Pain intensity

Due to the non-normal distribution in the pain scores, a Friedman’s ANOVA was performed to compare pain intensity between the three gain conditions (Median (IQR 25–75%): 4 (2.0, 6.0) in the 0.7 gain condition, 4 (3.0–7.0) in the 1.0 gain condition and 4 (2.75–6.0) in the 1.3 gain condition). There was no significant difference in pain intensity in different gain conditions (ꭓ²(2) = 1.39, p = 0.499).

Awareness of gain change

Sixty-two percent of all participants (46/74; the score of one participant was missing) reported not to have noticed a change in gain between the conditions (63% (N = 12/19) in the FABQ_pa fear group; 61% (n = 11/18) in the TSK fear group).

Motion sickness

During the VR submersion, the participants experienced either no symptoms (65%), mild symptoms but no nausea (17%), severe symptoms but no nausea (4%), mild nausea (8%) or severe nausea (5%) (see Table 3).

Table 3. Misery scores at the end of the experiment.

sMISC scores	All participants (N = 75)	No fear of movement (TSK≤37 & FABQ_pa≤14) (N = 46)^^/^*	Kinesiophobia (TSK>37) (N = 19)^*	Fear of physical activity (FABQ_pa>14) (N = 18)^**
0: No Nausea or other symptoms	49 (65.3%)	29 (63.0%)	11 (57.9%)	15 (83.3%)
1: Mild symptoms, but no nausea	13 (17.3%)	8 (17.4%)	4 (21.1%)	1 (5.6%)
2: Severe symptoms, but no nausea	3 (4.0%)	1 (2.2%)	2 (10.5%)	1 (5.6%)
3: Mild nausea	6 (8.0%)	6 (13.0%)	0 (0.0%)	0 (0.0%)
4: Severe nausea	4 (5.3%)	2 (4.3%)	2 10.5%)	1 (5.6%)
5: Vomiting	0 (0.0%)	0 (0.0%)	0 (0.0%)	0 (0.0%)

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Data are reported as number of patients (%).

* For one participant, data regarding the Tampa score was missing. Therefore, this participant was not included in one of the subgroups.

**For two participants, the FABQ_pa score was missing. Therefore, these participants were not included in one of the subgroups.

Discussion

This study revealed that fear of movement (as assessed by the TSK and the FABQ_pa subscale) influenced the susceptibility for the effect of visual feedback manipulation in people with non-specific neck pain. Regardless of whether people were fearful or not, this study confirmed that cervical pain-free range of motion can be influenced by visual perception of the amount of rotation. However, in people with fear of movement, the cervical pain-free range of motion was larger in the understated feedback condition compared to the control condition, and was smaller in the overstated feedback condition, while in people without fear, there was only a decrease in cervical pain-free range of motion in the overstated feedback condition. Furthermore, the difference in cervical pain-free range of motion between the understated and the overstated condition was larger in people with fear of movement compared to people without fear (i.e., a medium effect).

The age and sex of the participants in this study is representative for people with non-specific neck pain [48]. People with fear of movement were a distinguishable subgroup of the participants with neck pain, with higher scores for pain and dysfunction and a more limited cervical pain-free range of motion. This finding is consistent with previous findings [41, 42, 49–51], although correlations between fear and range of motion are inconsistent [41, 42, 52, 53]. Fearful people might share some similarities with people with anxiety disorders. Several studies in people with anxiety disorders showed deficits in classical conditioning, such as overgeneralisation (i.e., the process in which safe stimuli, which share some characteristics of the threatening conditioned stimulus, also lead to threat) [14, 54, 55]. The ability to discriminate between safe and threatening stimuli is conditional to avoid generalization. Differences between people with and without neck pain were found in the ability to distinguish ‘threatening’ cues from ’non-threatening’ cues [56]. This suggests that maladaptive associative learning might contribute to disability in people with neck pain who are fearful for movement.

In the current experiment we assumed that, based on associative learning, nociceptive stimuli and (non-nociceptive) visual stimuli had been coupled, and that the conditioned response (i.e., movement-evoked pain) could be influenced by manipulating visual feedback [2)] especially in fearful people. We found an effect of visual feedback manipulation on cervical pain-free range of motion and this effect was larger in people with fear of movement. In people who were fearful, the direction of the effect of visual feedback manipulation (i.e., a greater amplitude of pain-free movement in the understated condition versus a smaller amplitude in the overstated condition) was as expected. In people without fear, we did not find a greater amplitude of cervical pain-free range of motion when visual feedback reduced the perceived rotation angle compared to the control condition. This finding supports the idea that movement evoked pain has a protective or learned component in people with fear of movement. Our results in the fear groups regarding the effect of visual feedback manipulation were consistent with a previous study [2]. They also found an increase in range of motion in the understated condition (6%, 95%CI: 2%, 11%) and a decrease in range of motion in the overstated condition (7%, 95%CI: 3%, 11%) in people with neck pain (p<0.001, ղ_p² = 0.39). However, participant selection in that study (N = 24) was not based on the presence of fear, the gain change was 20% and the influence of fear was not studied. Another study in a larger sample (N = 75) of people with neck pain, that used a similar design and gain conditions of 0.8 and 1.2, found a small effect of visual feedback manipulation on cervical pain-free range of motion (p = 0.133, ղ_p² = 0.031) [7]. The role of fear was also not investigated in that study. This suggests that the susceptibility to modified visual feedback, may depend on the presence of fear of movement, and on the VR characteristics used. Based on the results in the current study and a comparison with previous studies [2, 7, 57] we consider that the magnitude of the gain change and alternating different VR environments may be important. The type of VR-environment seems less important, as another study shows that pain sensitivity was not modulated by VR-environment [58].

The lack of a strong interaction effect between kinesiophobia or fear of physical activity and visual feedback manipulation on cervical pain-free range of motion might have been due to the fact that (1) the sample of the group of fearful people was relatively small and (2) the contrast between people who were ‘fearful’ and ‘not fearful’ was relatively small. Mean TSK and FABQ_pa scores in the ‘fear group’ were close to the cut-off points to be considered fearful. People in the ‘fear group’ experienced mild/moderate fear, which is typical for people with neck pain in a primary care setting [59]. The results of our exploratory analysis, in which we increased the contrast between the groups by comparing participants who scored positive on both scales (N = 10: TSK≤37 & FABQ_pa≤14) with people with ‘no fear’ (N = 46), confirmed the impact of fear as the effect size was twice as large. However, due to the small number of people who scored positive on both questionnaires, these results should be interpreted with caution.

Although there was an effect of visual feedback manipulation on cervical pain-free range of motion independent of fear, in people who were not fearful of movement this effect was limited to the overstated condition and the change in range of motion between the understated and the overstated visual feedback condition was small (participants reduced their range of motion with -2.4% (95%CI: -2.2%, -2.7%)) in the overstated condition compared to the understated condition). We believe that for this group using overstated visual feedback to influence pain perception, may have little clinical utility. First, the absolute difference in total range of motion between the understated and overstated condition found in this study (2.6 degrees in the ‘no fear’ group) will not be detectable in a clinical setting without the use of accurate motion sensors. Second, no increase in cervical pain-free range of motion was found in the understated condition, while this is typically pursued in a therapeutic setting. Furthermore, a pilot study in 8 people with chronic neck pain, that was based on the hypothesis that overstated visual feedback could be used to reduce the association made between movement and pain (following the extinction principle) did not show that this reduced pain, even while VR was used for a longer period (21–28 days) [60]. In contrast, it might be that the use of VR has clinical relevance for people with moderate/severe fear of movement. Visualizing the relatively large change in cervical pain-free range of motion between the understated and overstated visual feedback condition (12.7%, 95%CI: 10.5%, 14.8%) in people with fear on both the TSK & FABQ_pa) may contribute to people’s understanding that non-nociceptive stimuli play a role in their pain experience. Moreover, exercising in an understated feedback condition might facilitate the use of a larger range of motion and influence the association made between movement and pain. Further research in which VR is applied with a large gain (i.e., a minimum of 30% gain) seems interesting to investigate whether this actually produces clinically relevant results in people with moderate/severe fear.

This experiment supports the view that cervical pain-free range of motion in rotation can be influenced by visual perception of the amount of rotation, in people with non-specific neck pain. People with fear of movement seem to be more susceptible for the effect of visual feedback manipulation than people without fear of movement. Because of the limitations mentioned, the results should be interpreted with caution.

Supporting information

S1 Appendix. Pilot study ‘creating illusions: Perception of gain changes when manipulating the visual feedback with virtual reality’.

(DOCX)

Click here for additional data file.^{(55.1KB, docx)}

S2 Appendix. Results of the data-analyses using the absolute data (range of rotation in degrees).

(DOCX)

Click here for additional data file.^{(69.6KB, docx)}

S1 Fig. Examples of the virtual reality environments projected in the VR-headset.

(DOCX)

Click here for additional data file.^{(2.3MB, docx)}

S1 Table. Exploratory analysis: Influence of visual feedback manipulation on cervical pain-free range of motion in people who scored positive or negative on both scales.

(DOCX)

Click here for additional data file.^{(14.9KB, docx)}

S1 Dataset

(SAV)

Click here for additional data file.^{(31.3KB, sav)}

Acknowledgments

The authors would like to thank the following students for their assistance in data collection: Theodora Karagianni, Sanne Akkermans, Sophie Boelen, Manouk Boer, Aytac Cakir, Thouria Loukili, Mandy Andriessen, Lisa Verhagen, Jorjen Neumann, Suzanne ten Hoor, Freek van der Velden, Jan van Splunter, Joey van Eeden, Laurens Sluiter and Ralph Laenen. This research did not receive financial support from funding agencies in the public, commercial, or not-for-profit sectors.

Data Availability

All relevant data are within the manuscript and its Supporting information files.

Funding Statement

The author(s) received no specific funding for this work.

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PONE-D-22-28987Visual feedback manipulation in virtual reality to influence pain-free range of motion. Are people with pain who are fearful of movement more susceptible?PLOS ONE

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PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: In this paper, the authors study how the manipulation of visual experience through the use of virtual reality can affect the perception of pain due to movement in participants with non-specific neck pain. The main result of the study is to have identified a greater amplitude of pain-free movement when visual manipulation reduces the perceived rotation angle compared to when it is increased. The effect reached significance only within the group without kinesiophobia.

The article is written in appropriate and easily understandable language. Data analysis, the process is fully described and seems to have been conducted appropriately in relation to the characteristics of the research.

An interesting aspect is also the easy transportability in the clinical practice of these types of procedures. However, the literature on these aspects is more extensive than perhaps transpires from what is presented in the introduction and could benefit from slight enrichment.

At the discretion of the authors, I believe that some passages could benefit from brief clarification or elaboration.

The statements in the abstract should be made more explicit and understandable. In particular, results and discussion could clearly report not only that effects have been identified but also in what direction these are going (i.e. effects on participants’ painless movements).

56 The concept of "non-specific neck pain" should be better defined.

66-67 and Fig.1A. The authors refer to another study, but a figure in reference (6) depicts the same subjects with the same experimental setup with the same caption as fig 1A, this may be confusing. Please clarify in the text, photo/picture caption, or both if necessary.

The authors in their manuscript provide all the necessary information. However, for the convenience of the reader, it would seem to me to be useful to indicate in the participants section some basic info (which the authors actually include in the first few lines of the results) in order to understand with more immediacy numerosity and demographic characteristics of the participants.

L91 Please be a little clearer about the exclusion criterion. Is the problem in vision or possible problems related to wearing an HMD while wearing glasses? Was corrected to normal vision using contact lenses was ok?

Genders are differently represented, and in the rest of the manuscript, there is no mention of gender except in the table. Please include explicitly in the text, either in the participant section or in the results and/or discussion, the rationale for this choice and some consideration of the role of this variable in the study.

167-170 Appropriate pilot study was used to test the recognition effect of manipulation on specific stimuli. Although in non-identical procedures, visual perspective manipulation via virtual reality is nonetheless present in the literature, and providing one or two insights might be appropriate for the manuscript and useful to the reader.

186 It might be interesting for the reader to have one or two examples of environments (e.g., 1 natural and 1 artificial) available directly in the manuscript from among the supplementary materials.

Also, about the environments used, it seems to me that the choice of the types of such environments is not discussed except to avoid possible learning effects and memorization of visual references. Two environments are natural and very bright, while four are artificial and dark. The literature addresses these types of differences from numerous perspectives, however, given the short duration of the exposures and the type of task, it may not be of particular relevance. However, it would be appropriate to include in the manuscript, also in the discussion (around lines 344-347 would seem appropriate to me), some brief consideration and reference regarding this choice and the possible implications of the characteristic qualities of the environment.

Reviewer #2: General comment - The aim of this study is clinically relevant and it will be of interest to clinicians. However, to be even more clinically and scientifically relevant, the results must be reinterpreted according to current guidelines in terms of p values.

Line 2 – “Are people with non-specific neck pain”?

Abstract

Line 36 – Specify “people with non-specific neck pain” and add the comparison group (fear vs no fear).

Line 37 – Specify the population (e.g., acute, subacute, chronic)? It would be nice to have this specification for the whole manuscript.

Line 39 – Replace “impact” with “effect” to be consistent.

Line 44 – A p-value > 0.05 does not mean that there is no effect. Actually, the effect is η² = 0.044. This effect is really close to the other one (η² = 0.06) with a p-value < 0.05. I advise you to read the American Statistical Association statement about p-values. It is not recommended to focus on the “statistical significance” (p < 0.05) anymore.

Introduction

Line 56 – It may be interesting to add a definition of “non-specific neck pain”, because you included traumatic neck pain in the sample and this type of neck pain is not always included in the “non-specific neck pain” population.

Line 58 – “that may be perceived as threatening”?

Line 66 – Again, it is not right to state that there was no effect only based on p-values. In interpreting the results, we should include the exact p-value, the effect size, and its 95%CI. Furthermore, it should be better to show the effects found in that study and then compare them with the effect found in the other one. If there are differences in effect sizes, it can be very interesting to find some possible explanations.

Lines 74-75 – “Individuals who are not fearful of movement may unlearn the association made between movement and pain, allowing pain to extinguish”. This is a strong hypothesis, because it says that pain can be extinguished only because of the unlearned association. However, not all people with non-specific neck pain have fear of movement, but they still suffer from pain.

Lines 78-79 - Maybe replace with "the aim for the current study was to evaluate whether the effect of visual feedback manipulation is greater in people with non-specific neck pain that are fearful of movement, compared to people with non-specific neck pain that are not»? Or something like that. However, in both cases, your hypothesis seems to be a superiority one (“more susceptible”). It will have an impact on the statistical hypothesis and testing used.

Methods and materials

General comment – The manuscript does not follow best practices for reporting. In addition, there is no registered protocol of the experiment.

General comment - You separated people with fear into two subgroups (TSK and FABQ-pa). I understand, but as you said earlier, these are two closely related constructs of fear. So why did you not combine them together into one group (“fearful people”)? And after that, it can be divided into two subgroups to see if there are some differences in the effect size.

Line 84 – What was the sampling method used? Was it probabilistic (random) or non-probabilistic (e.g., convenience, snowballing)? It should be specified as it impacts the generalizability of the findings.

Line 95 – “Based on an expected effect size of ηp² = 0.145 (i.e., 0.29/2)”. What is the basis for that? Why did you divide the effect by 2? If there is no specific reason, you should specified that it was arbitrary.

Line 110 – “motion sickness was evaluated”. Why? What information did it provide? Is it related to the purpose of the study?

Line 132 – Please add a reference for the cut-off score of FABQ-pa.

Line 143 – I don’t understand why this outcome is assessed. I don’t think there is a link with the purpose of the study. Is motion sickness susceptible to influence the pain-free ROM or another outcome? If yes, it should be specified in the introduction.

Line 184 – Please specify the method of randomization.

Line 186 – There are six environments. So, one environment per repetition for each condition? It is not clear.

Line 194 – “different”. Here you say "different" (equivalence or not), but the aim of the study was to evaluate whether the effect was greater in fearful subjects, to see if they are more susceptible (superiority or not). The hypotheses are not the same, as well as the type of p-value (one-sided or two-sided).

Line 194 - It is stated that there are only 2 groups (with fear and without fear), however in the analyses there are 3 groups (without fear, fear with TSK, fear with FABQ-pa). It needs to be clarified.

Line 195 – Why is the absolute data analysis not included in the manuscript?

Line 202 - Thresholds are not clearly distinct, there are overlaps (e.g., 0.059 is small or medium?).

Line 205 – “two subgroups”. In total there are 3 subgroups. Maybe you want to say that there are 2 subgroups per analysis? If yes, please specify.

Results

General comment – Results need to be reinterpreted according to the American Statistical Association statement on p-values. We should not use the “statistical significance” (p<0.05) to conclude if there is an effect or not. Results should be described with exact p-values, effect size, and its 95%CI. Adding the relative changes of range of motion would be great, as it allows readers to better understand the changes observed and to judge if they may be of clinical relevance (effect sizes in terms of η² might be difficult to interpret for clinicians).

Line 218 – In the methods it is stated that 40 subjects were needed (according to the sample size calculation, 20 per group). However, 75 people participated. Why?

Lines 221 to 223 – If I understand, you included people with fear of physical activity into the "no fear" group (compared to TSK), and you included people with kinesiophobia into the "no fear" group (compared to FABQ). If yes, I am not sure this is right because they are fearful in both cases. I don't think they can be considered as "no fearful". Including people with kinesiophobia or fear of physical activity in the “no fear” group may induce biases in the results as they are fearful in both cases. So, you compared “fearful” people with “fearful + no fearful” people.

Line 223 – “10 participants had fear according to both questionnaires”. So, these participants were included twice in the analyses? Once for TSK and once for FABQ-pa?

Line 225 – “no differences”. Based on what? If you refer to the p-values, please indicate the exact p-value. However, it would be interesting to add the values of age and duration of neck pain for both groups. As mentioned earlier, the p-value alone is not sufficient to state that there is a difference or not.

Lines 226-227 – “more disabled, scored higher on pain intensity and was more limited in the pain-free range of rotation”. Based on what? If you refer to the p-values, please indicate the exact p-value for each comparison. However, it would be interesting to add the values of pain intensity, disability, and ROM for both groups. As mentioned earlier, the p-value alone is not sufficient to state that there is a difference or not.

Line 230 – What about people with fear of physical activity?

Line 243 – “Numeric” rather than “Nummeric”.

Line 255 – It is not recommended to use the “statistical significance” anymore. Please read the American Statistical Association statement on p-values. It would be great to show the relative change in range of motion and its 95%CI where appropriate. In addition of the effect size, it gives a better idea of the effect (it is well done in the S3 appendix). Interpreting these effects as clinically relevant or not would also be a good idea.

Lines 263 to 266 – Do not use statistical significance. For example, you could say that “differences in range of motion between the overstated gain and the control condition (p=0.051, ղ2=0.052), and between the understated gain and the control condition (p=0.077, ղ2=0.044) were a bit smaller than the effect found between the understated and the overstated conditions”. Or something like that, to focus not on statistical significance but on effect sizes. Adding a 95%CI for effect sizes would also be good.

Line 272 – “conflicting” rather than “conflciting”. Why is it “conflicting”? Is it because the p-value is superior to 0.05?

Line 280 – “Median” rather than “mean”?

Line 283 – You indicated 75 participants before, now it is 76. Please correct.

Line 287 – I still don’t understand why this outcome is evaluated and its usefulness in this study.

Discussion

Line 303 – Replace “pain-related” by “pain-free” to be consistent.

Lines 306-307 – Can these factors play a role in the effects observed? If yes, it should be discussed. You do not mention these factors as potential confounders in the differences in the effects observed.

Lines 321 to 325 – First, the absolute range of motion scores are detailed in the S3 Appendix, however I am not sure that readers will look at it. These scores are discussed here without any specific reason, as you mentioned earlier in the manuscript that you would use the relative data (to account for differences in the overall neck range of motion). Why do you discuss the absolute changes and not the relative ones? In the manuscript, you only show the analyses for the relative data, but in the discussion, you only mention the absolute data. It is not clear. Second, these differences in absolute range of motion are on the order of 4-5 degrees for the total range of motion in rotation. Is it clinically relevant? I think it would be good to specify the clinical relevance of these findings.

Line 338 – Why is it convincing? What is your basis for that?

Line 343 - Again, "no effect" means that the effect size equals 0. Was it the case? Or just a p-value > 0.05?

Lines 367-368 – The conclusion is a bit too ambitious. I advise you to interpret according to the results. Maybe something like "In people with non-specific neck pain, those with fear of movement may be more susceptible for the effect of visual feedback manipulation than people without fear of movement. Because the effect sizes are small to medium and because of the limitations mentioned, the results should be interpreted with caution”. Results should also be interpreted according to the sample characteristics (more females, middle-aged people, duration of neck pain, mean pain intensity, disability). Please revise it in the abstract too.

S3 Appendix

Line 4 - The Kolmogorov-Smirnov test is used to assess normality. However, in the manuscript it is stated that normality is assessed via Q-Q plots and histograms. Why is it different here?

Lines 13 to 17 – Interaction effect was present in both cases, however it was no “significant” based on the “p<0.05” threshold. Please see the American Statistical Association statement about p-values. These results need to be reinterpreted.

Lines 13 to 30 – Are these mean changes clinically relevant?

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PLoS One. 2023 Jul 5;18(7):e0287907. doi: 10.1371/journal.pone.0287907.r002

Author response to Decision Letter 0

1 May 2023

Accompanying response letter

Reviewer # 1

Comments to the Author

In this paper, the authors study how the manipulation of visual experience through the use of virtual reality can affect the perception of pain due to movement in participants with non-specific neck pain. The main result of the study is to have identified a greater amplitude of pain-free movement when visual manipulation reduces the perceived rotation angle compared to when it is increased. The effect reached significance only within the group without kinesiophobia.

At the discretion of the authors, I believe that some passages could benefit from brief clarification or elaboration.

Abstract

1. The statements in the abstract should be made more explicit and understandable. In particular, results and discussion could clearly report not only that effects have been identified but also in what direction these are going (i.e. effects on participants’ painless movements ).

Response: We agree with this comment. We adjusted this in the abstract and reported the direction of the effects (lines 47-50).

2. Line 56 - The concept of "non-specific neck pain" should be better defined.

Response: Although this term is widely used, we can imagine that specifying the concept of 'non-specific neck pain' leads to more clarity. Therefore we defined it as ‘neckpain without a specific underlying pathology’1 (See line 39). A further specification of the characteristics of the participants is described in the selection criteria in the Methods section (See lines 93-100).

3. Lines 66-67 and Fig.1A. The authors refer to another study, but a figure in reference (6) depicts the same subjects with the same experimental setup with the same caption as fig 1A, this may be confusing. Please clarify in the text, photo/picture caption, or both if necessary.

Response: It is correct that we published a separate study using the same materials (e.g., VR headset, chair, fixation belt, computer) in an equivalent setting (as shown in the picture in figure 1A). However, this previously published article focused on different research questions, namely: (1) to determine whether pain-free range of motion increased and decreased when visual feedback understated or overstated true neck rotation with 20%, (2) to explore whether people with (long-lasting) chronic neck pain were more prone to the effect of visual feedback manipulation than people with subacute neck pain. This study did not address the effect of VR in people with fear of movement. So, the research questions from the current study generated from the first study, used different participants, different gain conditions (i.e., manipulation of the visual feedback with 30% rather than 20%) and different VR-environments. We clarified this in the picture (see figure 1). Despite similarities, the pictures differ from the pictures used in the previous publication. Taking into account point 8, we added two examples of the environments used to figure 1, and made this available directly in the manuscript.

4. The authors in their manuscript provide all the necessary information. However, for the convenience of the reader, it would seem to me to be useful to indicate in the participants section some basic info (which the authors actually include in the first few lines of the results) in order to understand with more immediacy numerosity and demographic characteristics of the participants.

Response: We added the info as requested in the Methods (see line 91).

5. Line 91 - Please be a little clearer about the exclusion criterion. Is the problem in vision or possible problems related to wearing an HMD while wearing glasses? Was corrected to normal vision using contact lenses was ok.

Response: We have adopted the reviewer’s suggestion and added ‘(e.g., people who had poor vision when not wearing their glasses as they could not be worn in the VR condition. The use of contact lenses was not a problem)’ to the description of the exclusion criteria (see lines 99-100)

6. Genders are differently represented, and in the rest of the manuscript, there is no mention of gender except in the table. Please include explicitly in the text, either in the participant section or in the results and/or discussion, the rationale for this choice and some consideration of the role of this variable in the study.

Response: We assessed gender to describe the sample. Indeed, in this study genders are differently represented. Considering the fact that neck pain between the ages of 45 and 64 is almost 50% more common in women than in men2, we belief that the distribution within this study reflects the population of people with nonspecific neck pain. We added this interpretation to the text (see line 346-347). We did not look at differences between men and women regarding the influence of fear. Due to the limited sample size of the fear group in this study, it was not possible to determine an effect of gender.

7. Lines 167-170 Appropriate pilot study was used to test the recognition effect of manipulation on specific stimuli. Although in non-identical procedures, visual perspective manipulation via virtual reality is nonetheless present in the literature, and providing one or two insights might be appropriate for the manuscript and useful to the reader.

Response: We agree with the reviewer that insights regarding visual perspective manipulation via virtual reality is present in the literature. However, to our best knowledge, the sensitivity to rate of change in gains (applied by redirected walking) is studied in other conditions (e.g. upper limb movements, gait), but is not described related to neck movements (apart from the references that were already mentioned in the study). In our previous study the use of a 20% gain did not influence pain free range of motion3. We expected that a larger change in gain was needed to induce an effect. However, we did not know if we could enlarge the gain without being noticed. Therefore we performed the pilot study that is referred to.

8. Line 186- It might be interesting for the reader to have one or two examples of environments (e.g., 1 natural and 1 artificial) available directly in the manuscript from among the supplementary materials.

Response: Two examples of the environments used are added to Figure 1 (C and D)

9. Also, about the environments used, it seems to me that the choice of the types of such environments is not discussed except to avoid possible learning effects and memorization of visual references. Two environments are natural and very bright, while four are artificial and dark. The literature addresses these types of differences from numerous perspectives, however, given the short duration of the exposures and the type of task, it may not be of particular relevance. However, it would be appropriate to include in the manuscript, also in the discussion (around lines 344-347 would seem appropriate to me), some brief consideration and reference regarding this choice and the possible implications of the characteristic qualities of the environment.

Response: As indicated in the introduction, conflicting results have been found in previous studies on the effect of visual feedback on pain-free range of motion. As suggested by the reviewer, a possible explanation for the different results between the two previous studies can be that different VR-environments were used (i.e., a countryside, park, mountain, church grounds, dining room and living room by Harvie et al.4, and different locations in one forest-environment by Kragting et al.3). In this study, we chose to use similar (indoor and outdoor) environments as used in the study of Harvie, to make the studies comparable and avoid bias. We included this consideration in lines 199-200.

Furthermore, a previous study that aimed to investigate the differential influence of multiple VR-environments on pain, reported that pain sensitivity was not modulated by context5. This information is used in the discussion (see line 377-378).

Reviewer: # 2

Comments to the Author

General comment - The aim of this study is clinically relevant and it will be of interest to clinicians. However, to be even more clinically and scientifically relevant, the results must be reinterpreted according to current guidelines in terms of p values.

Response: We agree with this reviewer’s remark. We added the confidence intervals in Table 2 and focused more on the effect sizes than on the statistical significance.

1. Line 2 – “Are people with non-specific neck pain”?

Response: We have incorporated this suggestion in the title.

Abstract

2. Line 36 – Specify “people with non-specific neck pain” and add the comparison group (fear vs no fear).

Response: We have specified the neck pain group (see line 39). The comparison group is described in lines 42-45.

3. Line 37 – Specify the population (e.g., acute, subacute, chronic)? It would be nice to have this specification for the whole manuscript.

Response: We have specified the population regarding the stage of the disorder (acute, subacute, chronic, long-lasting chronic) in Table 1 and added the IPQ 25-75% regarding ‘duration of neck pain’. In our opinion, this information is too detailed for an abstract. We decided not to include this specification (acute, subacute, chronic, long-lasting chronic) in the whole manuscript, as our previous study showed that the duration of neck pain had no impact on the effect of visual feedback manipulation on pain-free range of motion3.

4. Line 39 – Replace “impact” with “effect” to be consistent.

Response: Thank you for this comment. We replaced it (line 42).

5. Line 44 – A p-value > 0.05 does not mean that there is no effect. Actually, the effect is η² = 0.044. This effect is really close to the other one (η² = 0.06) with a p-value < 0.05. I advise you to read the American Statistical Association statement about p-values. It is not recommended to focus on the “statistical significance” (p < 0.05) anymore.

Response: We agree with the reviewer’s remark. We added the confidence intervals in Table 2 and focused more on the effect sizes, rather than on the statistical significance.

Introduction

6. Line 56 – It may be interesting to add a definition of “non-specific neck pain”, because you included traumatic neck pain in the sample and this type of neck pain is not always included in the “non-specific neck pain” population.

Response: We defined non-specific neck pain as ‘neck pain without a specific underlying pathology’1 (See line 61). A further specification of the characteristics of the participants is described in the selection criteria in the Methods section. (See lines 93-100).

7. Line 58 – “that may be perceived as threatening”?

Response: Thank you for this comment. We adjusted the sentence (line 63).

8. Line 66 – Again, it is not right to state that there was no effect only based on p-values. In interpreting the results, we should include the exact p-value, the effect size, and its 95%CI. Furthermore, it should be better to show the effects found in that study and then compare them with the effect found in the other one. If there are differences in effect sizes, it can be very interesting to find some possible explanations.

Response: In line with the general comment, the interpretation of the results of the studies we referred to in the introduction are based on the exact p-values, effect sizes and its 95%CI. In our opinion, it is unusual to include the explicit results of other studies in the introduction. A possible explanation for the different results between the two studies is given in the next paragraph (see lines 75-76).

9. Lines 74-75 – “Individuals who are not fearful of movement may unlearn the association made between movement and pain, allowing pain to extinguish”. This is a strong hypothesis, because it says that pain can be extinguished only because of the unlearned association. However, not all people with non-specific neck pain have fear of movement, but they still suffer from pain.

Response: We agree with the reviewer that in people with non-specific neck pain, there can be multiple reasons for the persistence of pain. In this study, we started from the hypothesis that pain may, partially, be a learned experience. We then propose a possible explanation for this hypothesis. To emphasize that it is an assumption, we have made the following adjustment ‘The underlying assumption is that individuals who are not fearful of movement may unlearn the association made between movement and pain, allowing pain to extinguish’ (see lines 80-81).

10. Lines 78-79 - Maybe replace with "the aim for the current study was to evaluate whether the effect of visual feedback manipulation is greater in people with non-specific neck pain that are fearful of movement, compared to people with non-specific neck pain that are not»? Or something like that. However, in both cases, your hypothesis seems to be a superiority one (“more susceptible”). It will have an impact on the statistical hypothesis and testing used.

Response: We agree with the reviewer that the objective of the study should have been formulated neutrally. We've adjusted this (see lines 84-86).

Methods and materials

General comment – The manuscript does not follow best practices for reporting. In addition, there is no registered protocol of the experiment.

Response: We followed the guidelines for reporting, however, we confirm that the protocol for the study was not published or registered.

Response: This comment of the reviewer made us reflect on our analyses. We formulated three different options how to modify our paper and sought advice from the Editor and reviewer (see Author Query 30-3-2023). Based on the advice received, we re-analysed our data (see comment 24).

11. Line 84 – What was the sampling method used? Was it probabilistic (random) or non-probabilistic (e.g., convenience, snowballing)? It should be specified as it impacts the generalizability of the findings .

Response: We added the sampling method used (see lines 92).

12. Line 95 – “Based on an expected effect size of ηp² = 0.145 (i.e., 0.29/2)”. What is the basis for that? Why did you divide the effect by 2? If there is no specific reason, you should specified that it was arbitrary.

Response: The design of the reference study (within comparisons)4 differed from the design of the current study (between-within), therefore we anticipated a smaller effect size. Indeed, the choice to divide the expected effect size by two was arbitrary. We specified this in the text (see lines 102-105).

13. Line 110 – “motion sickness was evaluated”. Why? What information did it provide? Is it related to the purpose of the study?

Response: We monitored motion sickness in this study. Motion sickness is a common side effect in VR, especially in people with neck pain and a possible barrier when considering implementing VR in clinical practice (see lines 119-121). Furthermore, in this study we increased the gain compared to other studies (i.e., manipulation of the visual feedback with 30% rather than 20%). In our opinion it is important to monitor this possible side effect, because it is a frequently mentioned phenomenon.

14. Line 132 – Please add a reference for the cut-off score of FABQ-pa.

Response: We added a reference for the cut-off score of the FABQpa (see line 141).

15. Line 143 – I don’t understand why this outcome is assessed. I don’t think there is a link with the purpose of the study. Is motion sickness susceptible to influence the pain-free ROM or another outcome? If yes, it should be specified in the introduction.

Response: Indeed, we have chosen not to include the evaluation of motion sickness in the objectives of the study. In our opinion this was a minor aim. An explanation for the choice made is given in comment 13.

16. Line 184 – Please specify the method of randomization.

Response: We specified the method of randomization in line 193-195.

17. Line 186 – There are six environments. So, one environment per repetition for each condition? It is not clear.

Response: To clarify the procedure we added ‘Hence, one environment was used per repetition for each condition’ to the sentence in line 198-199.

18. Line 194 – “different”. Here you say "different" (equivalence or not), but the aim of the study was to evaluate whether the effect was greater in fearful subjects, to see if they are more susceptible (superiority or not). The hypotheses are not the same, as well as the type of p-value (one-sided or two-sided ).

Response: As suggested by the reviewer in comment 10, we have reformulated our aim (see lines 84-86). This is in line with the formulation used in this section.

19. Line 194 - It is stated that there are only 2 groups (with fear and without fear), however in the analyses there are 3 groups (without fear, fear with TSK, fear with FABQ-pa). It needs to be clarified.

Response: In accordance with the advice, we performed 2 analyses with 2 subgroups per analysis (i.e., ‘no fear on both scales’ (TSK≤37 & FABQ-pa≤14) compared with ‘fearful for movement- kinesiophobia’ (TSK>37); and ‘no fear on both scales’ compared to ‘fear for physical activity’(FABQ-pa>14)). This is clarified in the text (see lines 206-211).

20. Line 195 – Why is the absolute data analysis not included in the manuscript ?

Response: As reported in the manuscript, we chose to report the relative data analysis in the main manuscript, because we wanted to anticipate expected differences between subjects (especially between people with and without fear of movement). Indeed, in the current sample the mean range of rotation differed between the people with and without fear of movement. To account for differences in the overall neck range of motion between subjects, for each participant, the data from the overstated and understated condition were transformed to a proportion of the mean range of rotation in the control condition (i.e., relative data). We have chosen not to include the absolute data-analysis in the main manuscript to avoid an overload of results, and thus confusion. Based on the reviewer's comment, we have decided to include the results of the absolute analyses in Table 2. We think this will support the clinician in interpreting the results.

21. Line 202 - Thresholds are not clearly distinct, there are overlaps (e.g., 0.059 is small or medium ?).

Response: Thank you for this comment. We made an adjustment (see lines 214-215).

22. Line 205 – “two subgroups”. In total there are 3 subgroups. Maybe you want to say that there are 2 subgroups per analysis? If yes, please specify.

Response: Thank you for this comment. We specified this (see line 217).

Results

Results are described with exact p-values and effect sizes. Both the absolute and relative changes in range of motion (including their 95%CI) are added in Table 2. We agree with the reviewer that this will support readers to better understand the changes observed and to judge if they may be of clinical relevance.

23. Line 218 – In the methods it is stated that 40 subjects were needed (according to the sample size calculation, 20 per group). However, 75 people participated. Why ?

Response: The subgroups (fear/no fear) were not equally distributed. We continued to enrol participants until we could include about 20 people with fear of movement.

24. Lines 221 to 223 – If I understand, you included people with fear of physical activity into the "no fear" group (compared to TSK), and you included people with kinesiophobia into the "no fear" group (compared to FABQ). If yes, I am not sure this is right because they are fearful in both cases. I don't think they can be considered as "no fearful". Including people with kinesiophobia or fear of physical activity in the “no fear” group may induce biases in the results as they are fearful in both cases. So, you compared “fearful” people with “fearful + no fearful” people .

Response: We agree with the reviewer that a positive score on one of the two scales may indicate a form of fear, which may have biased the results. Classifying the people who scored positive on the TSK, but negative on the FABQ-pa, in the 'no-fear of physical activity group’ probably made the contrast between the two groups smaller. The same applies to the analysis based on the TSK. In accordance with the advice from the reviewer (see email dd. 06-04-2023), we reanalysed the data and only included people who scored negative on both scales (TSK≤37 &FABQ-pa≤ 14) in the no fear group. We then also added an exploratory analysis in which people who were negative on both scales (N=46) were compared to participants who scored positive on both scales (N=10). The effect size is then twice as large (p=0.007, ղ2=0.112), confirming the impact of fear.

25. Line 223 – “10 participants had fear according to both questionnaires”. So, these participants were included twice in the analyses? Once for TSK and once for FABQ-pa ?

Response: as mentioned in our response in comment 19 & 24 we performed 2 separate analyses with 2 subgroups per analysis (i.e., ‘no fear on both scales’ (TSK≤37 & FABQ-pa≤14) compared with ‘fearful for movement- kinesiophobia’ (TSK>37); and ‘no fear on both scales’ compared to ‘fear for physical activity’(FABQ-pa>14)). So indeed, most participants were included twice in the analyses. As mentioned in comment 24 we also added an exploratory analysis (to enlarge the contrasts between the subgroups) in which people who were negative on both scales (N=46) were compared to participants who scored positive on both scales (N=10).

26. Line 225 – “no differences”. Based on what? If you refer to the p-values, please indicate the exact p-value. However, it would be interesting to add the values of age and duration of neck pain for both groups. As mentioned earlier, the p-value alone is not sufficient to state that there is a difference or not .

Response: To compare the participants characteristics between the subgroups, we performed statistical tests (independent sample t-tests or (in case of non-normality of the data) non-parametric Mann-Whitney tests). We chose to report values of age, duration, pain intensity, disability, kinesiophobia, fear of physical activity and ROM, including the results of the statistical tests, in Table 1 and not in the text, as these results do not answer the main research question and we intended to avoid duplication. Therefore, we suggest referring to the table for these data (as done in the original version)

27. Lines 226-227 – “more disabled, scored higher on pain intensity and was more limited in the pain-free range of rotation”. Based on what? If you refer to the p-values, please indicate the exact p-value for each comparison. However, it would be interesting to add the values of pain intensity, disability, and ROM for both groups. As mentioned earlier, the p-value alone is not sufficient to state that there is a difference or not.

Response: We specified in the text that ‘Table 1 provides an overview of the participant characteristics per group including the results from the comparisons between subgroups’ (see line 239-240).

28. Line 230 – What about people with fear of physical activity ?

Response: We added the result regarding mean ROM in people with fear of physical activity (see line 243).

29. Line 243 – “Numeric” rather than “Nummeric”.

Response: Thank you for this comment. We made an adjustment (see line 254).

30. Line 255 – It is not recommended to use the “statistical significance” anymore. Please read the American Statistical Association statement on p-values. It would be great to show the relative change in range of motion and its 95%CI where appropriate. In addition of the effect size, it gives a better idea of the effect (it is well done in the S3 appendix). Interpreting these effects as clinically relevant or not would also be a good idea.

Response: The exact p-values and effect sizes are described and the effect sizes are interpreted. The 95% CI are expressed in Figure 2 and Table 2. The absolute values (mean ROM and 95%CI) have been added in Table 2. This has informative value for the clinician.

31. Lines 263 to 266 – Do not use statistical significance. For example, you could say that “differences in range of motion between the overstated gain and the control condition (p=0.051, ղ2=0.052), and between the understated gain and the control condition (p=0.077, ղ2=0.044) were a bit smaller than the effect found between the understated and the overstated conditions”. Or something like that, to focus not on statistical significance but on effect sizes. Adding a 95%CI for effect sizes would also be good.

Response: As previously mentioned: results are described with exact p-values and effect sizes. Effect sizes are interpreted, and both the absolute as relative changes in range of motion (including their 95%CI) are added in Table 2.

32. Line 272 – “conflicting” rather than “conflciting”. Why is it “conflicting”? Is it because the p-value is superior to 0.05?

Response: We agree with the reviewer that the result of our prior analyses were not conflicting. We only found a small effect in the TSK group. The results of the recent analyses are in line with each other.

33. Line 280 – “Median” rather than “mean”?

Response: Thank you for this comment. Following Field (3th ed, p. 580)6, we have to report the test statistic, degrees of freedom and its significance. We made an adjustment (see line 315).

34. Line 283 – You indicated 75 participants before, now it is 76. Please correct.

Response: Thank you for this comment. We made an adjustment (see line 318).

35. Line 287 – I still don’t understand why this outcome is evaluated and its usefulness in this study.

Response: See response in comment 13

Discussion

36. Line 303 – Replace “pain-related” by “pain-free” to be consistent.

Response: Thank you for this comment. We checked the manuscript for the use of “pain-free”

37. Lines 306-307 – Can these factors play a role in the effects observed? If yes, it should be discussed. You do not mention these factors as potential confounders in the differences in the effects observed.

Response: It was expected that the differences in pain-free range of motion between the groups with and without fear of movement would influence the scores in the absolute data-analyses. Therefore the relative range of motion scores were used in the main analyses. This is already explained in the text (lines 187-191). It was not expected that the scores for pain and dysfunction were potential confounders, as a within design is used to test the effect of feedback manipulation on pain-free range of motion and the scores for pain and functioning were the same for each participant in the three gain conditions.

38. Lines 321 to 325 – First, the absolute range of motion scores are detailed in the S3 Appendix, however I am not sure that readers will look at it. These scores are discussed here without any specific reason, as you mentioned earlier in the manuscript that you would use the relative data (to account for differences in the overall neck range of motion). Why do you discuss the absolute changes and not the relative ones? In the manuscript, you only show the analyses for the relative data, but in the discussion, you only mention the absolute data . It is not clear. Second, these differences in absolute range of motion are on the order of 4-5 degrees for the total range of motion in rotation. Is it clinically relevant? I think it would be good to specify the clinical relevance of these findings.

Response: The absolute range of motion scores are easier to interpret, while the relative scores have no clear meaning for clinicians. However, we agree with the reviewer that it is strange to discuss the absolute data while in the rest of the manuscript the relative data were described. Therefore, this part is moved to the appendix. To make the relative data easier to interpret for clinicians, the change in pain-free range of motion is expressed in a percentage increase or decrease in range of motion.

39. Line 338 – Why is it convincing? What is your basis for that?

Response: This part of the text has been omitted in the revised version of the discussion

40. Line 343 - Again, "no effect" means that the effect size equals 0. Was it the case? Or just a p-value > 0.05?

Response: In this case we think we can say there is ‘no effect’, as the effect size is small, and the p-value high (p=0.133, ղp2=0.031).

41. Lines 367-368 – The conclusion is a bit too ambitious. I advise you to interpret according to the results. Maybe something like "In people with non-specific neck pain, those with fear of movement may be more susceptible for the effect of visual feedback manipulation than people without fear of movement. Because the effect sizes are small to medium and because of the limitations mentioned, the results should be interpreted with caution”. Results should also be interpreted according to the sample characteristics (more females, middle-aged people, duration of neck pain, mean pain intensity, disability). Please revise it in the abstract too.

Response: We believe that the first statement (‘This experiment supports the view that pain-free ROM can be influenced by visual perception of the amount of rotation (i.e., the main effect of gain, independent of the presence of fear)’) can be well substantiated by the results (TSK: p<0.001, ղp2=0.158; FABQpa: p<0.001, ղp2=0.195) -> large effect sizes. Given the medium effect sizes in both the analyses regarding the influence of fear (i.e., the interaction effect between fear of movement and visual feedback manipulation), we think that the interpretation that ‘People with fear of movement seem to be more susceptible for the effect of visual feedback manipulation than people without fear of movement’, is sufficiently consistent with the results (see lines 410-413).

S3 Appendix

42. Line 4 - The Kolmogorov-Smirnov test is used to assess normality. However, in the manuscript it is stated that normality is assessed via Q-Q plots and histograms. Why is it different here?

Response: We used the Q-Q plots, the histograms and the KS test to consider if the data were sufficiently normally distributed, so we have adjusted this in the text.

43. Lines 13 to 17 – Interaction effect was present in both cases, however it was no “significant” based on the “p<0.05” threshold. Please see the American Statistical Association statement about p-values. These results need to be reinterpreted.

Response: In accordance with the advice (see comment 24 and 25) we also re-analysed the data using the absolute range of motion scores. We performed 2 analyses with 2 subgroups per analysis (i.e., ‘no fear on both scales’ (TSK≤37 & FABQ-pa≤14) compared with ‘fearful for movement- kinesiophobia’ (TSK>37); and ‘no fear on both scales’ compared to ‘fear for physical activity’(FABQ-pa>14)). The analyses and results are reinterpreted, following the American Statistical Association statement. The confidence intervals are expressed in Table 2 and S3 Figure.

44. Lines 13 to 30 – Are these mean changes clinically relevant ?

Response: The mean changes in the ‘no fear’ group do not seem to be clinically relevant (as also discussed in the main manuscript (lines 390-398), while the changes in pain-free range of motion in the ‘fear of physical activity group’ and the ‘kinesiophobia’ group, might be clinically relevant. This is explained in lines 401-407.

References

1. Tsakitzidis G, Remmen R, Peremans L, et al. Non-specific neck pain: diagnosis and treatment. Good Clinical Practice (GCP) KCE Reports C. 2009;119.

2. Bier JD, Scholten-Peeters, G.G.M., Staal, J.B., Pool, J., Tulder, M. van, Beekman, E., Meerhoff, G.M. Knoop, J., Verhagen, A.P., . KNGF richtlijn nekpijn. In. Praktijkrichtlijn. Amersfoort: KNGF; 2016.

3. Kragting M, Schuiling SF, Voogt L, Pool-Goudzwaard AL, Coppieters MW. Using Visual Feedback Manipulation in Virtual Reality to Influence Pain-Free Range of Motion in People with Nonspecific Neck Pain. Pain Pract. 2020.

4. Harvie DS, Broecker M, Smith RT, Meulders A, Madden VJ, Moseley GL. Bogus visual feedback alters onset of movement-evoked pain in people with neck pain. Psychol Sci. 2015;26(4):385-392.

5. Smith A, Carlow K, Biddulph T, Murray B, Paton M, Harvie DS. Contextual modulation of pain sensitivity utilising virtual environments. Br J Pain. 2017;11(2):71-80.

6. Field A. Discovering Statistics Using SPSS. Third ed. London: Sage Publications Ltd; 2009.

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PLoS One. doi: 10.1371/journal.pone.0287907.r003

Decision Letter 1

Mariella Pazzaglia

29 May 2023

PONE-D-22-28987R1Visual feedback manipulation in virtual reality to influence pain-free range of motion. Are people with non-specific neck pain who are fearful of movement more susceptible?PLOS ONE

Dear Dr. Kragting,

Please submit your revised manuscript by Jul 13 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Mariella Pazzaglia

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

As you can see, the reviewer thinks your paper is potentially publishable but that some changes would be required.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #2: Yes

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6. Review Comments to the Author

Reviewer #2: Introduction

Lines 80-81 – The authors said “to emphasize that it is an assumption, we have made the following adjustment ‘The underlying assumption is that individuals who are not fearful of movement may unlearn the association made between movement and pain, allowing pain to extinguish’”, in relation to the comment number 9 (first revision). It's clearer that this is a hypothesis. However, my comment was more about the "allowing pain to extinguish" part. By saying this, the authors are assuming that the association between movement and pain is the only factor that determines the presence of pain. I'm not so sure about that. I think pain can be reduced, but not necessarily extinguished. I would suggest being more nuanced in the sentence and saying, for example, "allowing pain to be reduced".

Methods and materials

General comment – The authors have confirmed that they have followed reporting guidelines, but these are not mentioned in the manuscript. Please specify which reporting guidelines were followed in this manuscript.

Line 91 – I think that the first part of the sentence should be placed at the beginning of the results. The number of subjects is also written at line 238, but with different characteristics in brackets. It should be better to combine these two sentences in one (only the number of subjects and their characteristics) to avoid repetition.

Lines 119-121 – “Since motion sickness is a common side effect in VR (17), especially in people with neck pain (18), and a possible barrier when considering implementing VR in clinical practice, it was evaluated after the VR-experiment using the short version of the Misery Scale (sMISC)”.

Line 131 – “(FABQpa)” rather than “(FABQpa))”.

Line 132 – “Cut-off” rather than “cut-of”.

Line 212 – To be as complete and transparent as possible, I would suggest specifying that you will present results using exact p-values, the effect estimate and its 95%CI. Avoiding the use of the threshold "p<0.05" is not yet widespread in musculoskeletal research, so readers may be confused and wonder why you don't specify whether the results are statistically significant or not, if this is not stated here.

Results

Line 238 – My comment was: “In the methods it is stated that 40 subjects were needed (according to the sample size calculation, 20 per group). However, 75 people participated. Why?”. Authors responded: “The subgroups (fear/no fear) were not equally distributed. We continued to enroll participants until we could include about 20 people with fear of movement.”. I understand, but why didn't you keep the first 20 subjects with no fear of movement and only continue to enroll subjects with fear of movement? In any case, it's already been done. So, I suggest clarifying in the manuscript what you mentioned above, so that the reader is not confused about the difference between the sample size calculation and the final sample size.

Lines 244-245 – It says "In both groups" at the beginning of the sentence, but don't you mean "In both analyses"? I think it is not clear enough, because you have two fearful subgroups.

Line 250 – Add “pain-free” before “range of rotation” to be consistent.

Line 251 – Add “degrees” after “… with fear of physical activity 106.9 (38.4)”, to be consistent.

Table 1 – I don't think it's necessary to specify both sexes. In general, we only specify one sex (female or male), because if we know the numbers for one, we indirectly know the numbers for the other.

Line 265 – If you use a specific threshold for significance for these tests, you should specify which one you are using.

Lines 281-285 – At the beginning of the sentence (starting with “Contrasts…”) you compare pain free range of motion between the understated condition and the control condition, in fearful people, but in the next part of the sentence it is less clear. Do you talk about overstated versus control condition in fearful and non-fearful people, or do you compare fearful vs non fearful people in both conditions?

Line 282 – If you avoid using a specific threshold for statistical significance, it is best to avoid terms like “significantly”.

Lines 287-289 – The following part of the sentence is not clear for me: “decreased by 4.5%, 95%CI [-9.0%, 0.0%] (TSK) respectively 6.5%, 95%CI [-9.9%, -3.1%] (FABQpa) in the overstated condition.”. Could you rewrite it more clearly?

Line 289 – “This direction of the effect of visual feedback was as expected”. For me, this should be placed in the discussion.

Lines 289-290 – I had to reread the previous sentences to understand what the "overall effect" was. I think it would be a good idea to add in brackets what exactly it is.

Lines 324-325 – Same comment as for lines 289-290.

Lines 340-342 – For completeness and consistency, I would add the number of subjects with each type of symptom, in addition to the percentage (which is done in the previous section).

Discussion

Line 353 – What do you mean by “susceptibility to visual feedback manipulation”? Maybe “susceptibility for the effect of visual feedback manipulation”?

Lines 388-389 – My comment was: “Again, "no effect" means that the effect size equals 0. Was it the case? Or just a p-value > 0.05?”. Authors responded: “In this case we think we can say there is ‘no effect’, as the effect size is small, and the p-value high (p=0.133, ղp2=0.031)”. I don’t agree. To be consistent with the rest of the manuscript, authors should replace “no effect” with “small effect”.

Line 390 – Add “of” after “fear”.

Lines 408-421 – If you want to compare the fearful and non-fearful groups in the same way, you need to use the same relative changes. For non-fearful subjects, you're talking only about the change between the overstated condition and the control condition, whereas for fearful subjects, you're talking about the overall relative change. So, there's a big difference between the two groups.

Lines 426-427 – I would add “neck” before “pain-free range of motion” and specify that it is about rotation only. Sometimes you write “pain-free range of motion”, sometimes “cervical pain-free range of motion” and sometimes “neck pain-free range of motion”. Try to be consistent so that things are always written in the same way. In addition, I would clarify the population again. For example, the new sentence would be: “This experiment supports the view that neck pain-free range of motion in rotation can be influenced by visual perception of the amount of rotation, in people with non-specific neck pain”.

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Reviewer #2: No

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PLoS One. 2023 Jul 5;18(7):e0287907. doi: 10.1371/journal.pone.0287907.r004

Author response to Decision Letter 1

8 Jun 2023

Author response letter

Journal Requirements:

Comments to the Author

Response: We reviewed our reference list to ensure that it is complete and correct.

Reviewer: # 2

Comments to the Author

Introduction

1. Lines 80-81 – The authors said “to emphasize that it is an assumption, we have made the following adjustment ‘The underlying assumption is that individuals who are not fearful of movement may unlearn the association made between movement and pain, allowing pain to extinguish’”, in relation to the comment number 9 (first revision). It's clearer that this is a hypothesis. However, my comment was more about the "allowing pain to extinguish" part. By saying this, the authors are assuming that the association between movement and pain is the only factor that determines the presence of pain. I'm not so sure about that. I think pain can be reduced, but not necessarily extinguished. I would suggest being more nuanced in the sentence and saying, for example, "allowing pain to be reduced".

Response: We followed the suggestion and changed ‘extinguished’ to ‘reduced’ (lines 82-83)

Methods and materials

2. General comment – The authors have confirmed that they have followed reporting guidelines, but these are not mentioned in the manuscript. Please specify which reporting guidelines were followed in this manuscript.

Response: We added the reporting guideline to the manuscript (lines 111-112). Furthermore, we specified the study design in the Abstract (line 39) and we added the recruitment period to the Methods (line 92).

3. Line 91 – I think that the first part of the sentence should be placed at the beginning of the results. The number of subjects is also written at line 238, but with different characteristics in brackets. It should be better to combine these two sentences in one (only the number of subjects and their characteristics) to avoid repetition.

Response: We have followed this suggestion and removed the duplication (lines 242-243)

4. Lines 119-121 – “Since motion sickness is a common side effect in VR (17), especially in people with neck pain (18), and a possible barrier when considering implementing VR in clinical practice, it was evaluated after the VR-experiment using the short version of the Misery Scale (sMISC)”.

Response: Thank you for your suggestion. Given the length of the sentence, we chose to split the sentence (lines 121-123)

5. Line 131 – “(FABQpa)” rather than “(FABQpa))”.

Response: Corrected as suggested (line 133)

6 Line 132 – “Cut-off” rather than “cut-of”.

Response: Corrected as suggested (line 134)

7. Line 212 – To be as complete and transparent as possible, I would suggest specifying that you will present results using exact p-values, the effect estimate and its 95%CI. Avoiding the use of the threshold "p<0.05" is not yet widespread in musculoskeletal research, so readers may be confused and wonder why you don't specify whether the results are statistically significant or not, if this is not stated here.

Response: We agree with the reviewer’s suggestion. We specified this in the manuscript (lines 224-225).

Results

8 Line 238 – My comment was: “In the methods it is stated that 40 subjects were needed (according to the sample size calculation, 20 per group). However, 75 people participated. Why?”. Authors responded: “The subgroups (fear/no fear) were not equally distributed. We continued to enroll participants until we could include about 20 people with fear of movement.”. I understand, but why didn't you keep the first 20 subjects with no fear of movement and only continue to enroll subjects with fear of movement? In any case, it's already been done. So, I suggest clarifying in the manuscript what you mentioned above, so that the reader is not confused about the difference between the sample size calculation and the final sample size.

Response: We followed the reviewer’s comment and incorporated this suggestion (lines 244-246)

9. Lines 244-245 – It says "In both groups" at the beginning of the sentence, but don't you mean "In both analyses"? I think it is not clear enough, because you have two fearful subgroups.

Response: Thank you for identifying this. Changed as suggested. (lines 250)

10. Line 250 – Add “pain-free” before “range of rotation” to be consistent.

Response: Changed as suggested (line 256) and throughout the manuscript.

11. Line 251 – Add “degrees” after “… with fear of physical activity 106.9 (38.4)”, to be consistent.

Response: Changed as suggested (line 257)

12. Table 1 – I don't think it's necessary to specify both sexes. In general, we only specify one sex (female or male), because if we know the numbers for one, we indirectly know the numbers for the other.

Response: Changed as suggested and incorporated this in Table 1.

13. Line 265 – If you use a specific threshold for significance for these tests, you should specify which one you are using.

Response: Changed as suggested - We added whether we used t-test or Mann-Whitney U tests in Table 1.

14. Lines 281-285 – At the beginning of the sentence (starting with “Contrasts…”) you compare pain free range of motion between the understated condition and the control condition, in fearful people, but in the next part of the sentence it is less clear. Do you talk about overstated versus control condition in fearful and non-fearful people, or do you compare fearful vs non fearful people in both conditions?

Response: The contrasts reveal the differences between people with and without fear of movement in the understated condition compared to the control condition, and the differences between people with and without fear of movement in the overstated condition compared to the control condition. We modified the text to make this clear (lines 288-293).

15. Line 282 – If you avoid using a specific threshold for statistical significance, it is best to avoid terms like “significantly”.

Response: We agree with the reviewer. Changed as suggested. (line 289)

16. Lines 287-289 – The following part of the sentence is not clear for me: “decreased by 4.5%, 95%CI [-9.0%, 0.0%] (TSK) respectively 6.5%, 95%CI [-9.9%, -3.1%] (FABQpa) in the overstated condition.”. Could you rewrite it more clearly?

Response: We modified the text and wrote this part more clearly (see lines 293-300).

17. Line 289 – “This direction of the effect of visual feedback was as expected”. For me, this should be placed in the discussion.

Response: We agree and adjusted the manuscript accordingly (lines 391-393).

18. Lines 289-290 – I had to reread the previous sentences to understand what the "overall effect" was. I think it would be a good idea to add in brackets what exactly it is.

Response: Changed as suggested: we added “(i.e., the difference in pain-free range of motion between the understated and the overstated condition)” (lines 300-303)

19. Lines 324-325 – Same comment as for lines 289-290.

Response: Changed as above (lines 337-339)

20. Lines 340-342 – For completeness and consistency, I would add the number of subjects with each type of symptom, in addition to the percentage (which is done in the previous section).

Response: Unlike for the ‘previous section’, these percentages are already mentioned in Table 3. We prefer not to follow the suggestion of the Reviewer to avoid duplication.

Discussion

21. Line 353 – What do you mean by “susceptibility to visual feedback manipulation”? Maybe “susceptibility for the effect of visual feedback manipulation”?

Response: We have incorporated this suggestion (line 366).

22. Lines 388-389 – My comment was: “Again, "no effect" means that the effect size equals 0. Was it the case? Or just a p-value > 0.05?”. Authors responded: “In this case we think we can say there is ‘no effect’, as the effect size is small, and the p-value high (p=0.133, ղp2=0.031)”. I don’t agree. To be consistent with the rest of the manuscript, authors should replace “no effect” with “small effect”.

Response: Changed as suggested (line 403).

23. Line 390 – Add “of” after “fear”.

Response: Changed as suggested (line 406).

24. Lines 408-421 – If you want to compare the fearful and non-fearful groups in the same way, you need to use the same relative changes. For non-fearful subjects, you're talking only about the change between the overstated condition and the control condition, whereas for fearful subjects, you're talking about the overall relative change. So, there's a big difference between the two groups.

Response: We agree with the reviewer that when comparing the fearful and the non-fearful groups in the same way, we have to compare the relative changes in the same conditions. We therefore compared the overall relative change in both groups in the revised version of the manuscript (lines 424-430).

25. Lines 426-427 – I would add “neck” before “pain-free range of motion” and specify that it is about rotation only. Sometimes you write “pain-free range of motion”, sometimes “cervical pain-free range of motion” and sometimes “neck pain-free range of motion”. Try to be consistent so that things are always written in the same way. In addition, I would clarify the population again. For example, the new sentence would be: “This experiment supports the view that neck pain-free range of motion in rotation can be influenced by visual perception of the amount of rotation, in people with non-specific neck pain”.

Response: Changed as suggested. We preferred to use ‘cervical’ instead of ‘neck’. (lines 444-445)

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