Conditioned pain modulation elicited through manual pressure techniques on the cervical spine: a crossover study

Manual pressure techniques on the suboccipital muscles reduce pain sensitivity similar to the cold pressor test, indicating conditioned pain modulation activation as part of the working mechanism.

Abstract

Introduction:

Manual pressure techniques are commonly employed as a therapeutic approach for individuals experiencing musculoskeletal pain. The painful nature of these techniques suggests that a central mechanism known as conditioned pain modulation (CPM) might play a role.

Objectives:

This study tested whether a painful manual pressure technique (MPT) reduces pain sensitivity partly by eliciting a CPM effect.

Methods:

This crossover study examined 3 different conditioning stimuli: (1) a cold pressor test (CPT) with the contralateral hand submerged in a cold water bath, (2) painful MPT, and (3) sham-MPT on suboccipital muscles. We measured their effect on pain sensitivity using pressure pain thresholds at 3 locations: locally (suboccipital muscles), regionally (trapezius muscle), and remotely (tibialis anterior muscle).

Results:

In 63 healthy participants, no significant differences were found between the painful MPT and CPT on the pressure pain thresholds at all test locations: locally, −11 kPa (95% CI: 3 to −25); regionally, −15 kPa (95% CI: 10 to −39); and remotely, −24 kPa (95% CI: 55 to −7). Manual pressure technique compared to sham-MPT showed significant differences in the suboccipital muscles, −20.04 kPa (95% CI: −6.45 to −34.63) and the trapezius muscle, −38.24 (95% CI: −13.97 to −62.5) but no significant difference at the tibialis anterior muscle, −17.5 kPa (95% CI: 13.9 to −48.91).

Conclusion:

Painful MPTs applied at the suboccipital muscles reduce pain sensitivity at all sites, similar to the CPT, indicating CPM activation. Central pain inhibition might contribute to the effect of painful MPT in healthy people.

1. Introduction

In the field of physical therapy, hands-on techniques are commonly used to manage pain in musculoskeletal conditions. Among these techniques are the so-called myofascial inhibitory techniques and soft tissue techniques. These methods share the common feature of applying manual pressure and/or stress to myofascial structures and are collectively termed manual pressure techniques (MPTs). Manual pressure techniques have been widely described and studied in the lumbar and cervical spine regions, including in the suboccipital area.^11,23,24,34

For hands-on techniques accompanied by painful manual pressure or stress, the “pain inhibits pain” principle or conditioned pain modulation (CPM)⁴⁷ is supposed to be an underlying mechanism of action. The CPM paradigm is employed to evaluate the influence of descending controls on nociceptive processing. Generally, CPM can be considered the human surrogate measure of diffuse noxious inhibitory controls.³⁹ The CPM paradigm allows for the assessment of supraspinal endogenous descending inhibition and facilitation. Some of the structures that are supposed to be involved in these supraspinal nociceptive inhibitory pathways are the subnucleus reticularis dorsalis,^39,44 nucleus raphe magnus,⁸ and the periaqueductal grey (PAG).^19,27 Given the central action mechanisms of these structures, a local painful stimulus (the conditioning stimulus) administered on 1 side of the body can result in a reduction of pain sensitivity (test stimulus) on a remote side of the body.²⁰ Conditioned pain modulation is assessed by measuring pain sensitivity with and without a conditioning stimulus.⁴⁷ An effective and reliable method for measuring CPM involves utilizing cold pressor test (CPT) as a conditioning stimulus and pressure pain thresholds (PPT) as the test stimulus.^22,32

This study aimed to investigate the effect of painful MPTs as a conditioning stimulus applied to the upper cervical segments on pain sensitivity in healthy individuals. Moreover, we composed the following hypotheses: (1) The CPM effect due to the MPT as a conditioning stimulus is not different compared to the CPM effect induced by the CPT as a conditioning stimulus at all sites; (2) MPT as a conditioning stimulus leads to a larger CPM effect compared to the sham-MPT as a conditioning stimulus at all sites.

2. Methods

2.1. Study design

A crossover study was conducted. We tested the CPM effect of 3 types of potential conditioning stimuli: (1) the CPT, (2) the MPT, and (3) the sham-MPT with test stimuli on 3 different body locations. The study was approved by the Ethics Committee of the Vrije Universiteit Amsterdam, The Netherlands (VCWE-2021-062R1). The study is conducted according to the Declaration of Helsinki (2013) and reported following the STROBE guideline for cross-sectional studies (https://www.strobe-statement.org/checklists/).

2.2. Participants

Participants were recruited from social media and via advertisements at the Vrije Universiteit Amsterdam between May 2021 and March 2022. All participants had to provide written informed consent before participating in the study.

The inclusion criteria were individuals aged 18 to 65 who were pain-free. Exclusion criteria were regular use of analgesics and psychotropic medication, being pregnant or being less than 1 year postnatal and currently breastfeeding, being in the ovulatory phase of the menstrual cycle, a history of severe physical trauma (such as whiplash), having neurological or metabolic diseases (such as diabetes), and the presence of chronic pain syndromes (including fibromyalgia and migraine). Prior to the measurements, all participants were requested to refrain from caffeine-containing products,² alcohol²¹, and nicotine 4 hours before the measurement.^15,30 Pain medication or antidepressants had to be stopped 24 hours before the measurement. To prevent potential expectation bias, the participants had to be naïve to the CPM paradigm and PPT measurements.³¹

2.3. Procedures

All participants underwent 3 experiments in random order with the different conditioning stimuli (CS): (1) the CPT, (2) MPT, or (3) sham-MPT. The procedures were identical between the 3 experiments and consisted of familiarization, baseline measurements, and CPM measurements. Before familiarization, demographic data were collected. There was a 15-minute break between each experiment to reduce potential residual effects (Fig. 1). All experiments and measurements were conducted in 1 session of ∼90 minutes.

Figure 1.

Overview of the testing procedure. Panel (A): Overview of all steps. Panel (B): Detailed view of conditioned pain modulation (CPM) measurement containing baseline measurements of pressure pain thresholds (PPT) on 3 locations, followed by a 1-minute conditioning stimulus and directly after by the conditioned pressure pain thresholds. Panel (C): Visualization of quantification of CPM effect as the difference between the mean conditioned PPT and the mean baseline PPT.

Before, between, and after the measurements, all participants completed multiple questionnaires about demographic, psychosocial, and lifestyle factors to characterize the study population. These included the generalized anxiety disorder assessment (GAD-7) for anxiety,^26,40 the Kessler Psychological Distress Scale (K-10) for psychological distress,^12,38 the Pain Catastrophizing Scale (PCS) for pain catastrophizing,^10,45 and the Pittsburgh Sleep Quality Index (PSQI) for quality of sleep.⁵ The GAD-7 is a seven-item questionnaire with a maximum score of 21 points to assess generalized anxiety and demonstrated good internal consistency (alpha = 0.89) and convergent validity.²⁵ The K10 scale has excellent internal consistency (Cronbach alpha = 0.87) and a maximum score of 50 points, indicating severe distress, and a minimum score of 10 points, indicating no distress.⁴⁰ The PCS is a 13-item questionnaire to assess pain catastrophizing with a score of 0 to maximal 52 points with excellent internal consistency (Cronbach alpha: 0.92).⁴⁵ The PSQI is a self-report questionnaire to measure general sleep quality with a maximum score of 21 points and an internal consistency of Cronbach alpha of 0.68.⁵

Participants were in a lying, prone position in a temperature-controlled, low-noise room. The nondominant hand hung down the table, the other arm was placed next to the body, and both knees were positioned in 30-degree flexion during testing. This facilitated convenient access to the test locations while ensuring that the participant could remain comfortably reclined. Furthermore, the head was slightly tilted downwards to reach the suboccipital muscle appropriately.

All participants were familiarized with the algometry measurement at the extensor carpi radialis muscle on the nondominant side. Participants received standardized instructions and were asked to press the algometer switch when the sensation of pressure changed into pain. At least 3 familiarization measurements were conducted.

2.4. Test stimuli

Before and after each conditioning stimulus, PPTs were applied as test stimuli over 3 locations at the contralateral side of the conditioning stimulus: (1) occipital muscles, (2) trapezius descendens muscle, and (3) tibialis anterior muscle by 3 experienced assessors.⁷ For the MPT and sham-MPT, the occipital muscles and trapezius muscles are local and regional locations, and the tibialis anterior muscle is a remote location to determine a central effect.

A skin pencil was used to mark the measurement location on each muscle on the dominant side. A calibrated digital pressure algometer with a rubber tip of 1 cm² was used (Type II, Somedic AB, Stockholm, Sweden). The algometer was perpendicularly applied to the testing location with an increasing pressure rate of 50 kPa/s. Three consecutive PPT measurements were taken at each location with a 20 seconds interval to prevent wind-up.³⁶ The measurements at all 3 locations were executed in a fixed order starting with the suboccipital muscle, followed by the trapezius and the tibialis anterior muscle.

The achieved pressure in kPa was noted as the PPT outcome. An incorrect measurement (defined here as >30% difference compared to the mean of the other 2 measurements) was directly deleted and remeasured.

2.5. Conditioning stimuli

2.5.1. Cold pressor test

A sequential protocol with the CPT was used.^36,47 The setup utilized in this study consisted of a temperature-controlled water bath designed to maintain a maximum temperature variance of ±0.5°C. The water bath was equipped with a circulating pump to ensure continuous circulation of ice water. The water temperature was 10 to 12°C. The participants were asked to immerse their nondominant hand in the cold water bath. After 60 seconds,⁴⁷ the participant was asked to withdraw the hand out of the water and rate the perceived pain during the conditioning stimulus from 0 (no pain) to 10 (worst possible pain) on an 11-point numeric pain rating scale (NPRS). The PPT tests were performed directly afterwards, without compromising the blinding of the assessor.

2.5.2. Manual pressure technique

The MPT was performed by 2 clinicians with >15 years of experience in MPTs at the cervical spine. The MPT was applied with 1 thumb of the therapist placed on the suboccipital muscles at the nondominant side. The clinician slowly increased the pressure to achieve a pain score in the range of NPRS 5 to 6/10. A timer was started immediately after, and the pressure was held for 60 seconds, equal to the CPT.⁶ Every 20 seconds, the participant was asked to rate the pain (due to a potential habituation effect and potential fluctuation of the pressure given interacting with the experienced pain). In any case, it needed to exceed 4/10, a level deemed adequate to induce a CPM response.³⁷ When the initial pain intensity decreased during the test, the pressure was raised till a minimum pain score of 4 out of 10 was achieved. During the application of the MPT, the thumb pressure of the therapist was measured using force-sensing resistor (FSR) sensors placed on the tip of the thumb and registered by CAPTIV software (https://est-kl.com/manufacturer/tea/captiv-software.html). These sensors measure the applied pressure in g/cm².

2.5.3. Sham manual pressure technique

The sham-MPT was applied with the clinician's thumb with a force sensor placed on the suboccipital muscle at the nondominant side without causing a painful or uncomfortable feeling. The clinician held the same pressure for 60 seconds. Equal to the other 2 conditioning stimuli, the participants were asked to rate their perceived pain during the conditioning stimulus on the NPRS 0 to 10 point scale.

2.5.4. Randomization and blinding

A computer-generated randomization schedule determined the order of the conditioning tests and allocated one of the assessors and clinicians to every participant. A research assistant monitored the randomization of participants, assessors, and clinicians. Another blinded research assistant was responsible for the data collection and logistic operations. To ensure that the assessors conducting the PPT measurements remained blinded to the sequence of the 3 conditioning stimuli, they only entered the examination room after the conditioning stimulus had been applied. The clinicians administering the MPT or CPT held the sensors on their thumbs and mimicked drying the participant's hand.

2.5.5. Calculations

For all conditioning stimuli, the absolute and the relative CPM effect was analyzed per location.⁴⁷ First, the mean of 3 PPT measurements before the conditioning stimulus was used to calculate the baseline PPT. Second, the absolute CPM effect of the CPT, MPTs, and sham-MPTs at each location was calculated by subtracting the mean conditioned PPT score (after applying the conditioning stimulus) from the mean baseline PPT. A negative value indicates an inhibitory CPM effect. The relative CPM effect was determined by calculating the percentual difference in PPT after the conditioning stimulus compared to the baseline PPT (ie, [conditioned PPT-baseline PPT]/baseline × 100).⁴⁷

Before statistical analysis, Gaussian outlier removal was used to increase the robustness of analyses. Outliers were defined as more than 3 standard deviations from the mean, as these observations would have less than a 0.3% chance of being present while highly influencing the results of the analyses.³⁵

2.5.6. Sample size

G*Power (3.1.9.7) was used with a General Linear Models with a Repeated Measures approach to estimate the fixed effects of the Linear Mixed Models analysis.^9,13 The sample size estimation was further based on a power of 0.90, a significance level of 0.05, a correlation among repeated measures of 0.5, and an effect size of f = 0.20 (small to medium). The calculation resulted in a total of a minimum of 55 participants. To account for possible missing values (eg, due to early retraction of the hand during the CPT), a sample size of 65 was needed.

2.6. Statistical analysis

Descriptive statistics were performed to describe participants' characteristics. Data were reported as mean (SD) in normally distributed data. Linear mixed model analyses with maximum likelihood were used to analyze the effects of the conditioning stimulus per location, including the estimated means. The conditioning stimulus was used as a fixed factor, the participant as a random effect, and the order of the conditioning stimulus was used as a covariate to control for carry-over effects. An autoregressive covariance structure was used for the repeated measure structure. The addition of random intercepts and slopes was based on −2 log-likelihood tests. Post-hoc tests on the estimated means were adjusted for multiple comparisons using the Bonferroni adjustment.

All statistical analyses were performed in SPSS version 28 (IBM, Armonk, NY) with a significance level of α = 0.05.

3. Results

Sixty-three participants were included and completed all measurements. The sociodemographic characteristics are summarized in Table 1. The mean (SD) force during the MPT was 1112 (11.2) g/cm². The mean pain intensity during the test was for the CPT: 6.56 points (95% CI: 6.32–6.78), the MPT: 6.25 points (95% CI: 6.01–6.47), and the sham-MPT as a control stimulus: 0.69 points (95% CI: 0.46–0.92). There was no statistically significant difference in pain intensity between the CPT and MPT.

Table 1.

Participant characteristics (n = 63).

Characteristic	Mean ± SD
Age, y (SD)	32.8 (12.9)
Gender, male (%)	32 (50.8%)
Smoking, currently (%)	7 (11.1%)
Generalized anxiety, GAD-7 (SD)	3.3 (3.2)
Psychological distress, K-10 (SD)	15.5 (5.2)
Pain catastrophizing, PCS (SD)	7.2 (5.7)
Sleep, PSQI (SD)	4.2 (2.9)

GAD-7, generalized anxiety disorder; K-10, Kessler Psychological Distress Scale; PCS, pain catastrophizing scale; PSQI, Pittsburgh sleep quality index; SD, standard deviation.

Table 2 outlines the mean absolute and relative CPM effects, presented as Δ PPT scores (in kPa), for each conditioning stimulus location.

Table 2.

Absolute and relative conditioned pain modulation effect per location for the cold pressor test, manual pressure techniques, and sham manual pressure techniques.

	Cold pressor test Mean ± SD	Manual pressure technique Mean ± SD	Sham-manual pressure technique Mean ± SD
Absolute values (ΔkPa) of CPM effect
Occipital muscles	−13.1 ± 42.7	−24.4 ± 38.4	−4.3 ± 38.9
Trapezius desc. muscle	−20.0 ± 61.2	−34.7 ± 83.6	3.5 ± 66.7
Tibialis ant. muscle	−44.8 ± 102.0	−20.4 ± 93.7	−2.9 ± 75.7
Relative values (Δ%) of CPM effect
Occipital muscles	−4.9 ± 14.5	−8.9 ± 13.8	−1.1 ± 11.0
Trapezius desc. muscle	−7.0 ± 14.7	−8.8 ± 19.2	1.1 ± 14.4
Tibialis ant. muscle	−8.4 ± 15.5	−5.9 ± 16.4	0.1 ± 13.1

CPM, conditioned pain modulation; kPa, kilopascal; SD, standard deviation.

3.1. Absolute conditioned pain modulation effect between conditioning stimuli

Compared to the CPT, MPT showed no significant absolute differences in PPT at the suboccipital muscles (−11.2 kPa [95% CI: 2.53 to −24.99], P = 0.108), the trapezius muscle (−14.71 kPa [95% CI: 9.55 to −38.97], P = 0.233), and tibialis anterior muscle (24.37 kPa [95% CI: 55.44 to −6.7], P = 0.123). These results confirm hypothesis 1; MPT and CPT are not significantly different.

Significant absolute differences were found for MPT on PPT compared to sham-MPT in the suboccipital muscles (−20.04 kPa [95% CI: −6.45 to −34.63], P = 0.004) and the trapezius muscle (−38.24 kPa [95% CI: −13.97 to −62.5], P = 0.002). This difference was not significant at the tibialis anterior muscle (−17.5 kPa [95% CI: 13.9 to −48.91], P = 0.272). These results reject hypothesis 2; MPT is not significantly different from sham. Figure 2 presents the absolute CPM effects of the 3 different conditioning stimuli.

Figure 2.

Absolute CPM effect per conditioning stimulus per location in kilo Pascal (kPa). A negative value indicates an inhibitory effect. Hypothesis 1 is confirmed on all locations. ^aHypothesis 2 is rejected at the tibialis anterior muscle. *Statistically significant, P < 0.05. CPM, conditioned pain modulation.

3.2. Relative conditioned pain modulation effect between conditioning stimuli

In comparison with CPT, the MPT resulted in similar relative increases in PPT across all 3 locations: suboccipital muscles −4% [95% CI: 0.44 to −8.37] P = 0.077, trapezius muscle: −1.81% [95% CI: 3.67 to −7.3], P = 0.51, tibialis anterior muscle: 2.52% [95% CI: 7.61 to −2.58], P = 0.33, confirming hypothesis 1 that MPT and CPT are not significantly different. Hypothesis 2 was also confirmed as MPT demonstrates significant differences at all 3 locations compared to sham-MPT: suboccipital muscles −7.74% (95% CI: −3.38 to −12.1), P < 0.001; trapezius muscle −9.88% (95% CI: −4.3 to −15.47), P < 0.001; and tibialis anterior muscle −5.96% (95% CI: −0.81 to −11.11), P = 0.024. Figure 3 shows the relative CPM effects for the 3 conditioning stimuli.

Figure 3.

Relative CPM effect per conditioning stimulus per location in percentage change from baseline. A negative value indicates an inhibitory effect. Hypothesis 1 is confirmed at all locations. *Statistically significant, P < 0.05. CPM, conditioned pain modulation.

4. Discussion

4.1. Main findings

Manual pressure technique resulted in a CPM effect that was not significantly different from the CPT in both absolute and relative PPT scores at the suboccipital muscles, the trapezius, and the tibialis anterior muscles. The MPT stimuli showed a significantly larger absolute and relative CPM effect than the sham-MPT, except for the absolute difference of MPT compared to sham-MPT at the tibialis anterior muscle. Overall, our results indicate that MPT applied at the cervical-occipital region induces a CPM effect similar to a CPT.

Across locations, the magnitude of the absolute and relative CPM effect differs between the CPT and the MPT. The CPT has a larger effect on the tibialis anterior muscle than the MPT, while the MPT has a larger CPM effect on the occipital and trapezius muscles. Although local effects of the MPT, caused by pressure and stretching of suboccipital myofascial structures, seem to play a role, the CPM effect of the MPT at the suboccipital muscles is not significantly different compared to other test locations where local effects are lacking. This suggests not only local working mechanisms for the effect of hands-on techniques but also the involvement of a neurophysiological explanatory model.⁴ We hypothesized that mechanical nociceptive stimulation by manual pressure techniques at the occipital muscles would activate the ventrolateral periaqueductal grey (vlPAG) and, thereby, endogenous pain inhibition at the same somatotopic levels. Compared to the CPT, our results show that mechanosensitivity most increases at the contralateral occipital and trapezius sites, indicating supraspinal endogenous nociceptive inhibition in the cervical region and less at the tibialis anterior muscle. Cold pressor test produces a greater relative PPT increase at the tibialis anterior muscle compared to the neck region. This result is in line with the findings of Oono et al.,³³ where CPT showed the greatest relative increase in PPT at the tibialis anterior muscle site compared to a tourniquet at the upper arm and mechanical pressure to the head. Also, Reezigt et al.³⁶ showed a larger CPM effect by CPT at the tibialis anterior site than at the trapezius site. This difference in response between CPT and MPT may be not only depend on the type of conditioning stimulus (thermal vs mechanical) but also on the anatomical site where the conditioning stimulus is applied as shown by our results that align with the study of Granovsky et al.¹⁶ where a central applied conditioning stimulus reported a greater CPM effect than a peripheral-located stimulus at the trapezius test site.

One study reported that pain-inducing massage on a trigger point in the trapezius muscle and CPT in a pain-free population showed no significant differences and concluded that the results of both conditioning stimuli were consistent with a CPM response.⁴⁶ Another study described the association between the analgesic response of a trigger point massage at the trapezius muscle and the analgesic response of CPM in asymptomatic participants and found a significant correlation between the analgesic effect of CPM and mild trigger point massage (r = 0.53, P = 0.002) and intensive trigger point massage (r = 0.73, P < 0.001).⁴¹

In a recent study by Arribas-Romano et al., healthy students were divided into 3 groups to compare different interventions: MPT interventions, electrical stimulation, and the cold pressor test.¹ Results indicated that the painful MPT (5/10 on NPRS) showed significantly increased PPT values at the tibialis anterior muscle than less painful or nonpainful MPT (2/10, 0/10 NPRS) interventions. Moreover, the CPT produced a significantly greater decrease in PPT than MPT (5/10) (−0.77; CI 95% [−1.53 to −0.02]). Our study differs from Arribas-Romano et al., regarding the measurement protocol, test locations, and calculation. Following the CPM recommendations, we applied a sequential CPM protocol measuring test stimuli at 2 sites (an upper and a lower limb) and reported both absolute and relative outcomes for the CPM effect.⁴⁷ The relative values are recommended because absolute values alone do not fully capture the differences between pre- and postconditioning stimuli. Displaying both absolute and relative differences allows researchers to assess the raw effectiveness of the conditioning stimulus and its efficacy compared to the baseline values. Moreover, we applied the cold pressor test (10–12 degrees Celsius) and the MPT for 1 minute, unlike the 2 minutes used by Arribas-Romano et al. Furthermore, all 63 participants underwent both MPT and sham-MPT to all 63 participants with identical timing for the conditioning stimuli.

A notable difference between our population and Arribas-Romano et al.'s was the mean age (and range) of participants, with our population being slightly older, which may explain the baseline differences in sensitivity. Since younger age is considered to produce greater CPM effects,¹⁸ this difference in age and conditioning stimuli duration between the studies could potentially explain the difference in the absolute CPM effect found at the tibialis anterior muscle. While age-related mechanosensitivity variation exists, it also enhances the generalizability of our results.

We used CPT as a conditioning stimulus and PPT as a test stimulus and measured the test stimuli at the contralateral side of the applied conditioning stimulus at different and remote locations as being the most reliable measurement to assess CPM in healthy participants.^25,32

In addition, we selected the commonly used trapezius muscle midpoint as a reliable and regional test location for mechanosensitivity, assuming that the CPM effect at all sites would be in the same direction as the local test location.

The test stimuli were measured in a fixed order. However, randomization of the first location would have been an alternative to minimize potential residual CPM effects.

The MPT as a conditioning stimulus was designed to provoke a painful stimulus to induce supraspinal descending nociceptive inhibition. To optimize the effect of this intervention, the researcher placed the thumb on the suboccipital muscles. The reason for this specific anatomical location is based on experimental research in animals and humans concerning the representation, connectivity, and transmission of sensory information between the myofascial structures in the upper cervical segments and the vlPAG as an essential driver and key-structure of supraspinal descending nociceptive inhibition.^29,42,43 This is recently demonstrated in an fMRI study on the somatotopography of the PAG, showing that the most cranial part of the PAG corresponds mainly to the C2 and C3 segments.²⁹ Activating endogenous descending antinociception of the vlPAG by a painful MPT intervention at the upper cervical segments may, therefore, initiate an inhibitory effect, specifically targeting the C2 and C3 segments within the trigeminocervical complex.

Based on the CPM paradigm “pain inhibits pain,” we hypothesized that the painful MPTs should first result in nociceptive afferent activity of Aẟ and C fibres from muscles and skin, initiating hyperexcitability at the dorsal horn levels C0-3.^3,43 Subsequently, a decrease in excitation by supraspinal endogenous inhibition is expected.¹⁷ The results of our study confirmed this hypothesis for the relative outcomes but not for absolute outcomes at all sites.

Although the not-painful sham was not assumed to affect CPM, the sham intervention may have initiated touch-induced analgesia. This tactile analgesia appears to be partly dependent on the modulatory function of Aβ fibres on Aδ and C pathways at the spinal level but also seems to be mediated at the brainstem level by subcortical neural circuitry.^14,28 The PPT scores show that participants reacted to the sham conditioning stimuli; however, as expected, their reactions were not significant, variable, and less pronounced compared to the other 2 conditioning stimuli.

4.2. Limitations of the study

The load in time and attention may have influenced the results. This potential attention bias was reduced by asking the participants to fill in questionnaires during the breaks and by alternating the different stimuli.

Only healthy participants were included in our study, limiting the generalization of results to patients with (chronic) pain conditions. The next step, therefore, is to examine MPTs and determine the CPM effect in patients with headaches and other musculoskeletal pain conditions.

4.3. Clinical implication

Alleviating pain through the application of painful manual pressure techniques may be beneficial for individuals demonstrating effective descending pain inhibition. Identifying central modulatory mechanisms of MPTs may provide a better understanding and strengthen clinical decision-making when to use these techniques. For people lacking a descending pain inhibitory response or those having a facilitatory response, the use of MPTs may not be beneficial.

5. Conclusion

Manual pressure techniques applied to the suboccipital muscles initiate a CPM effect based on relative outcomes. In addition to local mechanisms, central pain inhibition is supposed to play a role in the effect of painful manual pressure techniques in healthy people.

Disclosures

The authors have no conflict of interest to declare.