Music interferes with expectation-induced pain modulation: a controlled cross-over experimental study

Supplemental Digital Content is Available in the Text.

Music is more effective than an audiobook to reduce pain, but both interventions reduce the hyperalgesia/hypoalgesia induced by high/low pain expectations.

Abstract

Introduction:

Music reduces pain and anxiety in various contexts, but the possible effect on pain anticipatory mechanisms remains unclear.

Objectives:

This study examines the effects of a standardized musical intervention (Music Care) on pain perception and on pain modulation induced by expectations of low or high pain.

Methods:

Healthy participants were tested in an experimental study using a crossover design involving the musical intervention counterbalanced with an active auditory control condition (audiobook) and a silent control condition. Pain perception was assessed using contact heat stimulation, and expectations were manipulated using prestimulus anticipatory cues signalling high or low pain.

Results:

Perceived pain intensity, measured using a visual analog scale, was decreased during the music intervention and the audiobook compared to silence (P's < 0.001). Music was more effective than the audiobook control, especially at the higher pain stimulation level (P < 0.001). Anticipatory cues modulated pain and anxiety in the expected direction across all conditions (P's < 0.001). Music and the audiobook produced comparable reduction in (1) expectation-induced (1a) hypoalgesic and (1b) hyperalgesic effects (all P's < 0.005) and in (2) pain anticipatory anxiety (all P's < 0.05). Overall, music was more effective than the active auditory control to reduce pain but both forms of auditory distraction partly blocked the modulatory effects of low and high pain expectations.

Conclusion:

This study highlights the multiplicity of processes contributing to music-induced analgesia and suggests that music may help improve pain management in the context of high pain expectation and anxiety. However, music may also interfere with pain-relieving strategies involving the induction of low pain expectations.

1. Introduction

Music is an essential part of culture and traditional healing rituals, yet its integration into modern health care is, at best, considered complementary.³⁴ The 2023 Global Year for Integrative Pain Care of the International Association for the Study of Pain (IASP) promotes new approaches to pain management and highlights the need to improve our understanding of their underlying mechanisms (see https://www.iasp-pain.org/publications/iasp-news/the-iasp-2023-global-year-for-integrative-pain-care/). Translational research is needed to explain how music modifies pain experiences.

Several factors contributing to the efficacy of music interventions have been identified. The control over the choice of musical excerpts³⁶ and individual preferences^56,57 are recognized ingredients of effective interventions. In addition to a distracting effect, the induction of a positive affect by music that listener's find pleasant also contributes to its analgesic effects and/or to the reduction of pain-related anxiety.^38,43,53 These responses possibly involve the activation of the brain reward system^10,18,55,62 but may be independent from the endogenous opioid system.⁴⁵ This implies that music may reduce pain indirectly by neutralizing negative cognitive and affective factors that normally increase pain.

The fear-avoidance model of pain describes how anticipatory cues eliciting pain expectation can increase pain perception.⁵⁹ Experimental studies have shown that expectations of high or low pain produce the corresponding changes in pain perception through endogenous modulatory systems.^3,13,23 Music may potentially help improve pain management by neutralizing hyperalgesic expectations.

In the present study, a cross-over experimental design is applied in healthy volunteers to test the effects of music, compared to an active auditory control (audiobook) and a silence condition, on (1) acute heat pain, (2) pain modulation by expectations of high or low pain intensity, and (3) pain-related anticipatory anxiety. To optimize translational relevance, a music app designed for clinical applications (Music Care) was used that allows for a standardized and personalized intervention considering individual preferences. This application was previously used by our group in a clinical study showing a reduction in the burden of care in dental implant surgery⁶ and has demonstrated its efficacy to reduce pain-related anxiety in randomized controlled trials conducted in various clinical conditions.⁵⁴ We hypothesized that (1) music will reduce acute heat pain perception and that (2) music will interact with the effect of anticipatory cues signaling high pain by reducing the hyperalgesic effect of high pain expectations. We also tested (3) the effect of music on the anxiety elicited by the high pain anticipatory cue. Secondarily, the experimental design allows testing (4) the nonspecific effect of music on expectations by comparing its impact in the high and low pain cue conditions.

2. Methods

This registered protocol is available at Open Science Framework (https://osf.io/s98w7; see minor deviations in Supplementary Material, http://links.lww.com/PR9/A331).

2.1. Participants

Thirty-six healthy adult participants (19 men, 16 women, 1 unreported; mean age = 27.7± 11.0 y.o.) were recruited through word of mouth, posters, or digital advertisements posted at University of Montreal and on social media. Exclusion criteria included neurological or psychiatric disorders, presence of any serious illnesses (eg, cancer or cardiovascular disease), hearing loss, and taking psychotropic or analgesic medication, or recreational drugs. The experimental procedures were approved by the local ethics committee (Project #CER VN 18-19-25), and all participants provided written informed consent and received a compensation (75$ Can). Participants were not told about the specific hypotheses on music and expectations and were simply informed that the study investigated various forms of auditory stimulation.

2.2. Study design

Each participant completed 3 testing sessions to compare: (1) Music Care, (2) Audiobook (active control), and (3) Silence Control (order counterbalanced).

2.3. Thermal stimuli and pain ratings

Thermal stimuli were delivered using a 3 × 3-cm contact thermode applied alternatively to 4 skin sites on the volar surface of the left forearm (MEDOC, TSA-II Neurosensory Analyser, Ramat Yishai, Israel) with a delay of at least 2 minutes between successive stimulation of the same site. Stimuli were delivered between 40°C and 50°C (rise/fall in 2.5 seconds; plateau of 8 seconds). Pain was rated on a visual analog scale (VAS; 0-No pain to 100-Worst pain imaginable).^50,51

2.4. Interventions

The experiment was conducted in a quiet room, and participants wore earphones in all conditions (Sennheiser OCX 686 SPORTS). Participants were given a computer tablet to choose their preferred music from 7 original instrumental pieces (piano ballad, Folk guitar, Celtic music, music from movies, Cuban music, classical music, and Andean music) composed following specifications provided by the creator of Music Care (see https://www.music.care/en/index.html). The Music Care protocol used was the U-sequence as shown in Figure 1 and described in previous studies.^{25–30,34,39,46,47,54} In the audiobook control condition, participants chose one of 7 books provided by the experimenter (see Suppl. Materials, http://links.lww.com/PR9/A331). Participants were given a short summary of each book and listened to a 1-minute excerpt. The audiobooks had no background music, were selected to avoid strong emotional content, and were read by professional readers with a relatively neutral tone. The silence control condition was conducted with the earphones on with no audio intervention.

Figure 1.

Experimental procedure. (A) Time course of a session. After the Music or Audiobook selection, the thermal calibration was conducted to select 3 target temperatures to produce low, moderate, and high pain. The auditory intervention then began for 5 minutes before the learning phase and continued throughout the learning and test phases. The learning phase is composed of 12 trials with valid cue-stimulus contingencies. The test phase contains 16 valid cue-stimulus pairs and 8 invalid cue-stimulus pairs. The invalid pairs are always composed of a moderate pain stimulus preceded by a low (4 trials) or a high (4 trials) pain cue to assess the effects of low or high (vs moderate) pain expectation on the pain produced by the moderate pain stimulus. Note that the proportion of trials with low–moderate–high pain cues is maintained to 1/3 each throughout the learning and test phases so that there was no explicit or implicit information provided to the participant on the change in cue-stimulus contingencies from the learning to the test phase. (B) U-Sequence in Music Care. The music intervention followed the U-sequence developed by Music Care to provide a progression of the musical arrangement intended to facilitate the induction of a relaxed state. (C) Time course of an experimental trial. After the anticipatory cue, the stimulus temperature increased to reach low, moderate, or high pain and then returned to baseline. The participant provides a rating of the pain felt after each stimulation using keyboard keys to move a cursor over the VAS displayed on the computer screen.

2.5. Procedure

The 3 sessions took place at the same time of the day on different days within 2 weeks (except for one participant tested over a 6-week period).

Participants first selected their preferred music or book (Fig. 1A) and underwent a pain calibration phase in silence to select temperatures to produce low, moderate, and high pain. After calibration, the music, audiobook, or control silence period began. Participants were free to close their eyes during a 5-minute initial auditory stimulation and were then asked to open them to see the pain anticipatory cues and to rate pain.

2.5.1. Calibration

Pain was assessed using the method of constant stimuli, following a standard procedure applied routinely in our lab (5 × 7 intensities between 40°C and 50°C). This calibration procedure took about 20 minutes and allowed calculating a stimulus-response function to determine 3 temperatures selected to produce low, moderate, and high pain, based on target ratings of 30/100, 65/100, and 80/100 on the pain VAS, respectively.

2.5.2. Manipulation of expectations

In the learning phase (about 10 minutes), 12 stimuli were administered after a valid visual cue (6-12 seconds) signaling the level of pain to be expected (low/moderate/high). In the test phase (about 20 minutes), 24 trials were administered with modified cue-stimulus contingencies (Fig. 1). Most trials were preceded by a valid cue (n = 16), and the others were preceded by an invalid cue suggesting a higher (n = 4) or lower (n = 4) stimulus magnitude. After blocks of 12 trials, subjects were asked to rate the level of anticipatory anxiety (0-100 VAS) evoked by the low, moderate, and high pain cue. This experimental model of expectation-induced pain modulation has been validated in previous studies.^2,3,40,48

2.6. Statistical analysis

The sample size was determined using G*Power (V. 3.1.9.4) to detect a medium effect size (ANOVA, within-subject, f = 0.25), at α = 0.05 and 1 − β = 0.90, and assuming a correlation or r = 0.50 between the repeated measures across subjects (see https://osf.io/s98w7).

Statistical analyses were conducted as planned using SPSS v. 26, by one of the team members (P.R.) who was kept blind to the coding of the interventions. Significance was set to P < 0.05, and all follow-up contrasts were adjusted using the Bonferroni correction. Partial eta-squared (partial η²) is reported to describe the effect size (small = 0.01, medium = 0.06, large = 0.14). Pairwise contrasts are calculated to help interpret interactions, and the Means and SD of each condition are reported in Supplementary materials, http://links.lww.com/PR9/A331.

The effect of music on pain perception was assessed using a 3 × 3 repeated measures ANOVA comparing the 3 interventions and the 3 stimulus temperatures. The significant interaction was decomposed by calculating an analgesic score for the music and audiobook intervention (vs silence). An additional analgesic score was calculated by subtracting pain in the music condition from the audiobook condition to assess the superiority of music analgesia.

The effect of music on expectation-induced pain modulation was assessed using a 3 × 3 repeated measures ANOVA comparing the 3 interventions and the 3 anticipatory cues for the moderate pain stimulus condition only. To decompose this interaction, we calculated the hyperalgesic and the hypoalgesic expectation effects by subtracting pain from the moderate pain cue condition from the high and low pain cues, respectively.

The effect of music on anxiety elicited by the anticipatory cues was tested in a 3 × 3 repeated measures ANOVA to compare the 3 interventions and the 3 anticipatory cues.

Exploratory correlational analyses (Pearson-r) were conducted to test the association between the modulation of pain by music (vs silence, and vs audiobook) and the corresponding changes in anticipatory anxiety. Similarly, correlation analyses were computed to assess if the effects of music (vs silence, and vs audiobook) on expectation-induced hyperalgesia and hypoalgesia was associated with the corresponding changes in anticipatory anxiety. Given the exploratory nature of those analyses, they are reported with bilateral uncorrected P-values.

3. Results

Data from all participants are included in the results. Means and standard deviations of all dependent variables are reported in Supplementary Tables S1-S5, http://links.lww.com/PR9/A331.

3.1. Effects of music on pain

The mean pain ratings displayed in Figure 2A are consistent with the target levels determined in the calibration procedure, and the results of the ANOVAs are reported in Table 1.

Figure 2.

Effects of the interventions on pain perception. (A) Pain ratings reported to the low, moderate, and high stimulus intensity in the Silence, Audiobook, and Music condition. Main effects of, and interaction between, intervention (3) and stimulus (3) are significant at P < 0.001, and all pairwise contrasts are significant at P < 0.05 except for Music vs Audiobook at the low stimulus intensity (P = 0.055). (B) The interaction is further illustrated by change scores calculated for each participant with positive Pain Decrease indicating a hypoalgesic effect of the Audiobook and Music conditions compared to Silence, and of the Music condition compared to the Audiobook. Results of the ANOVA comparing the hypoalgesic effects of Music and Audiobook (difference from Silence) confirmed the main effects of, and interaction between, intervention (2) and stimulus (3) significant at P < 0.001. The interaction term indicates that the superiority of Music over the Audiobook is significantly larger at the high vs moderate stimulus intensity. Each dot represents one subject in each condition, and the Boxplot represents interquartile intervals. Results of the ANOVA are detailed in Table 1B, and Means (SDs) are reported for each condition and contrast in Supplementary Tables S1 and S2, http://links.lww.com/PR9/A331.

Table 1.

Effects of the interventions on pain perception.

	F	Df*	P	pη2	Pairwise comparisons†
A. Pain perception‡
Intervention (3)	35.8	1.77, 70	<0.001	0.97	All pairwise contrasts P < 0.001
Stimulus intensity (3)	1157.9	1.69, 70	<0.001	0.51	All pairwise contrasts P < 0.001
Intervention × stimulus	13.7	2.53, 35	<0.001	0.28	All pairwise contrasts P < 0.001 except music vs audiobook at the low stimulus: P = 0.055 (ns); and the moderate stimulus: P = 0.012 (sig)
B. Analgesic effect of music and audiobook (difference from silence)‡
Intervention (2)	17.45	1, 35	<0.001	0.33	Music analgesia > audiobook
Stimulus intensity (3)	16.1	1,51, 58.8	<0.001	0.32	Low vs moderate: P = 0.51 (ns) Moderate vs high: P < 0.001
Intervention × stimulus intensity	9.8	1.55, 54.2	<0.001	0.22	Music analgesia > audiobook for low pain: P = 0.018; Moderate pain: P = 0.004; and high pain: P < 0.001

(A) The first section reports the results of the ANOVA evaluating the effects of the Intervention (3) Music, Audiobook, and Silence (control) and of Stimulus intensities (3; low, moderate, and high) on pain ratings. (B) The second section reports results of the ANOVA comparing the analgesic effect of the Music and the Audiobook conditions, calculated as the absolute difference in pain from the Silence condition, examined across the 3 stimulus intensity levels.

^*Degrees of freedom adjusted using the Greenhouse–Geisser correction if applicable.

^†Pairwise contrasts adjusted using the Bonferroni correction; sig, significant; ns, not significant.

^‡Means and SDs are reported in Supplementary Table S1 and S2, http://links.lww.com/PR9/A331.

There was a significant main effect of intervention on pain. Lower pain was reported overall in the music condition compared to both silence and the audiobook (all pairwise contrasts P < 0.001). There was also a significant main effect of stimulus intensity on pain (all pairwise contrasts P < 0.001). Furthermore, there was an interaction between intervention and stimulus intensity (P < 0.001) suggesting that the analgesic effect varied with the intensity of the stimulus. Both main effects and the interaction were very large (partial η² = 0.28–0.97; see Table 1).

Follow-up analyses confirmed a larger analgesic effect of music compared to the audiobook (P <0.001; partial η² = 0.33). This effect was observed for low, moderate, and high pain (P's < 0.05; see Fig. 2B and Table 1B). The superiority of music was significantly larger in the high pain intensity conditions compared to the moderate and the low pain intensity conditions (P's < 0.01), but it did not differ between the moderate and low pain intensity conditions (P = 0.81). These results confirmed the superiority of the music condition, especially for more intense pain.

3.2. Effects of music on expectation-induced pain modulation

The pain ratings of the moderate stimulus intensity are displayed in Figure 3A, and the analyses of the effect of the intervention on pain modulation induced by anticipatory cues are reported in Table 2.

Figure 3.

Effects of the interventions on pain modulation induced by anticipatory cues. (A) Pain ratings in response to the moderate stimulus intensity preceded by anticipatory cues signaling a low (invalid), moderate (valid), or high (invalid) pain stimulus in the Silence, Audiobook, and Music condition. Main effects of, and interaction between, intervention (3) and anticipatory cue (3) are significant at P < 0.001, and all pairwise contrasts are significant at P < 0.05 except for Music vs Audiobook in the low cue condition: P = 0.12. (B) The interaction is further illustrated by change scores calculated for each participant with the hypoalgesic expectation effect indicated by a negative pain modulation value (Low − Moderate Pain cue), and hyperalgesic expectation effect indicated by a positive pain modulation value (High − Moderate Pain cue). Results of the ANOVA indicated that the modulation of pain by the anticipatory cues was reduced significantly by Music and the Audiobook in both the hypoalgesic (P's < 0.05) and hyperalgesic (P's < 0.005) conditions. There was no indication of a differential effect of Music vs the Audiobook on expectation-induced hypoalgesia (P = 1.00) or hyperalgesia (P = 0.38). Results of the ANOVA are detailed in Table 2, and Means (SDs) are reported for each condition and contrast in Supplementary Tables S3 and S4, http://links.lww.com/PR9/A331.

Table 2.

Effects of the interventions on pain modulation induced by anticipatory cues signaling different levels of pain when administering the moderate pain stimulus.

	F	Df*	P	pη2	Pairwise comparisons†
A. Pain perception‡
Intervention (3)	18.0	1.8, 63.4	<0.001	0.34	Music vs silence: P < 0.001 Audiobook vs silence: P = 0.004 Music vs audiobook: P = 0.018
Anticipatory cue (3)	265.5	1.1, 37.4	<0.001	0.88	Hyperalgesic effect of the high vs moderate pain cue: P < 0.001 Hypoalgesic effect of the low vs moderate pain cue: P < 0.001
Intervention × anticipatory cue	10.3	2.1, 74.1	<0.001	0.23	Cue effect  All pairwise contrasts: P < 0.001 Intervention effect  Low pain cue: all P > 0.12 (ns)  Moderate pain cue: all P < 0.05  High pain cue: all P < 0.05
B. Hypoalgesic expectation effect‡ (low − moderate pain cue)
Intervention (3)	6.51	1.96, 68.5	0.003	0.16	Music > silence§: P = 0.010 Audiobook > silence§: P = 0.016 Music vs audiobook: P = 1.00 (ns)
C. Hyperalgesic expectation effect‡ (high − moderate pain cue)
Intervention (3)	12.3	1.93, 67.5	<0.001	0.26	Music < silence‖: P < 0.001 Audiobook < silence‖: P = 0.004 Music vs audiobook: P = 0.38 (ns)

(A) The first section reports the results of the ANOVA evaluating the effects of the Intervention (3: Music, Audiobook, and Silence-control), and of the anticipatory cue (3; low, moderate, and high pain) on pain ratings. The second and third sections of the table report results of the ANOVA comparing the 3 interventions on (B) the hypoalgesic effect of the low pain cue and (C) of the hyperalgesic effects of the high pain cue (difference in pain ratings from the moderate pain cue condition).

^*Degrees of freedom adjusted using the Greenhouse–Geisser correction if applicable.

^†Pairwise contrasts adjusted using the Bonferroni correction; sig, significant; ns, not significant.

^‡Means and SDs are reported in Supplementary Table S3 and S4, http://links.lww.com/PR9/A331.

^§The hypoalgesic effects of the low pain anticipatory cue is reduced in the Music and Audiobook conditions compared to Silence (ie, less decrease induced by low pain expectations; see Fig. 3).

^‖The hyperalgesic effects of the high pain anticipatory cue is reduced in the Music and Audiobook conditions compared to Silence (ie, less increase induced by high pain expectation; see Fig. 3).

There was a very large and significant main effect of the anticipatory cue on pain (P < 0.001, partial η² = 0.88). A hyperalgesic effect was observed after the high vs the moderate pain cue, and a hypoalgesic effect was observed after the low vs the moderate pain cue (P's < 0.001). These effects confirmed the efficacy of the expectation manipulation on pain.

The ANOVA also indicated an interaction between intervention and the expectation effects (P < 0.001, partial η² = 0.23). The hypoalgesia produced by low pain expectation was reduced significantly in both the music and audiobook condition (P's < 0.05; see Fig. 3B and Table 2B). This reduction in expectation-induced hypoalgesia was almost identical in the music and the audiobook condition (P = 1.00). Similarly, the hyperalgesic effect was reduced in both the music and the audiobook condition (P's < 0.005; Fig. 3B and Table 2C). This reduction in expectation-induced hyperalgesia was similar across the music and the audiobook condition (P = 0.38). These results indicate that music and the audiobook interfered to a comparable extent with the effects of high and low pain expectation.

3.3. Effects of music on pain-related anticipatory anxiety

The mean anxiety ratings are displayed in Figure 4, and the analyses of the effect of the intervention on anxiety are reported in Table 3.

Figure 4.

Effects of the interventions on anxiety induced by the anticipatory cues. Anxiety induced by the anticipatory cues signaling a low, moderate, or high pain stimulus is reported for the Silence, Audiobook, and Music condition. Main effects of the interventions and the anticipatory cue are significant at P < 0.001, and the interaction is significant at P = 0.004. Pairwise contrasts confirmed the significant decrease in anticipatory anxiety in both the Music and the Audiobook conditions compared to Silence (all P's < 0.005). No significant difference was found between the Music and the Audiobook in the moderate (P = 1.00) and high (P = 0.98) pain cue condition. A very small but significant effect was observed in the low cue condition (P = 0.004). Results of the ANOVA are detailed in Table 3, and Means (SDs) are reported for each condition in Supplementary Table S5, http://links.lww.com/PR9/A331.

Table 3.

Effects of the interventions (3) on anxiety induced by the anticipatory cues (3) signaling different levels of pain (interventions: music, audiobook, and silence-control; anticipatory cues: low, moderate, and high pain).

	F	Df*	P	pη2	Pairwise comparisons†
Anticipatory anxiety‡
Intervention (3)	25.6	1.94, 67.8	<0.001	0.42	Music vs silence: P < 0.001 Audiobook vs silence: P < 0.001 Music vs audiobook: P = 0.44 (ns)
Anticipatory cue (3)	175.2	1.22, 42.7	<0.001	0.83	All pairwise contrasts P < 0.001
Intervention × anticipatory cue	5.06	2.62, 91.9	0.004	0.13	Cue effect for each intervention  All pairwise contrasts: P < 0.001 Intervention effect for each cue  Music vs silence: All P < 0.001  Audiobook vs silence: All P < 0.005 Music vs audiobook  Low pain cue P = 0.004  Moderate pain cue P = 1.00  High pain cue P = 0.98

^*Degrees of freedom adjusted using the Greenhouse–Geisser correction if applicable.

^†Pairwise contrasts adjusted using the Bonferroni correction; sig, significant; ns, not significant.

^‡Means and SDs are reported in Supplementary Table S5, http://links.lww.com/PR9/A331.

There was a large and significant main effect of the anticipatory cue (P < 0.001, partial η² = 0.83) with more anxiety reported after the high vs moderate pain cue, and the moderate vs the low pain cue (all P's < 0.001). There was also a large and significant main effect of the intervention on anticipatory anxiety (P < 0.001, partial η² = 0.42). The music and the audiobook conditions resulted in lower anticipatory anxiety (P's < 0.001) but did not differ significantly from each other (P = 0.44).

The ANOVA also revealed a significant interaction between the intervention and the anticipatory cue (P = 0.004, partial η² = 0.13). The music and the audiobook conditions produced a significant reduction in mean anticipatory anxiety across all pain cues (P's < 0.005; Fig. 4). Almost identical reductions were produced by the music and the audiobook condition after the high and the moderate pain cue (P > 0.97). The interaction reflected a significant advantage of the music compared to the audiobook in reducing the anxiety induced by the low pain cue (P = 0.004; Fig. 4). However, the absolute magnitude of this advantage was very small and may reflect a floor effect. Taken together, these results indicate that music and the audiobook were effective to a comparable extent in reducing anticipatory anxiety when moderate and high pain are expected.

3.4. Exploratory analyses

Additional analyses showed that music-induced hypoalgesia (Fig. 2) correlated to the reduction in anticipatory anxiety (Fig. 4) for the high pain intensity (r = 0.42, P = 0.01; ns for moderate or low pain, P's > 0.10). The superior hypoalgesic effect of music compared to the audiobook was also associated with a larger effect of music on anticipatory anxiety (high pain: r = 0.41, P = 0.01; ns for moderate or low pain, P's > 0.15). A small association was also observed suggesting that individuals reporting less anticipatory anxiety (Fig. 4) also reported smaller expectation-induced hyperalgesia (Fig. 3A) (r = 0.36, P = 0.03). No significant association was found in the audiobook and silence conditions (r's < 0.10, P's > 0.60).

Finally, we tested the relation between (1) the differential effect of the music intervention (vs silence and vs audiobook) on expectation-induced hyperalgesia (Fig. 3) and (2) the corresponding effect on anticipatory anxiety (Fig. 4). The reduction in hyperalgesia in the music condition (vs silence) was not significantly related to the corresponding reduction in anticipatory anxiety (r = 0.22, P = 0.19). Nevertheless, participants showing a larger reduction in hyperalgesia in the music vs the audiobook condition also reported a larger reduction in anxiety in the corresponding contrast (r = 0.34, P = 0.04). These results indicate that the effects of music on expectation-induced pain modulation were largely independent from changes induced by the interventions on anticipatory anxiety but that the superiority of music over the audiobook might relate, to a small extent, to changes in anxiety.

4. Discussion

The results support the superiority of music compared to an audiobook intervention. However, music and the audiobook reduced the hyperalgesic effect of high pain expectations and the hypoalgesic effects of low pain expectations to a comparable extent. Similar reduction in anticipatory anxiety was also observed in both the music and the audiobook condition but changes in anxiety accounted for only a small part of pain reduction. These results provide novel insights on the psychological mechanisms underlying the effects of music on pain-related processes by demonstrating a combination of nonspecific components affecting pain expectations and anticipatory anxiety, and other components possibly more specific to music.

4.1. Music is more effective than an active auditory control intervention

Both auditory interventions reduced pain, but music produced larger improvements. This indicates that the effect of music cannot be explained simply by a nonspecific auditory distraction. Using the same music app, Soyeux and Marchand⁵⁶ further showed that most-liked music resulted in greater analgesia than least-liked music in response to acute thermal pain. However, the advantage of preferred music, including using one's own music, was not confirmed statistically in a meta-analysis on surgical pain and anxiety.⁴³ The musical pieces used here were judged as more relaxing and pleasant than the audiobooks excerpts in our previous clinical study.⁶ This implies that the superiority of music observed here may relate to positive affective responses induced by music. However, we cannot disentangle a possible confound induced by the specific material used here from a potential effect inherent to music.

It has also been suggested that a greater sense of control over musical choice is a more important parameter than the emotional responses related to musical excerpts.³⁶ However, in our study, participants were allowed to choose both the music and the audiobook. Thus, the superiority of music for inducing hypoalgesic effects is unlikely to be explained solely by a greater sense of control over the selection of preferred stimuli.

4.2. Potential mechanisms

With increasing clinical interest in the integration of standardized interventions to improve pain and anxiety management,⁵⁴ experimental research has shifted towards the understanding of potential regulatory processes triggered by music. Music has been found to reduce central sensitization induced by the temporal summation of pain.⁶¹ This might involve the activation of cerebro-spinal pathways, consistent with the inhibition of the spinally mediated nociceptive flexion reflex by pleasant music.⁵² However, a reduction in the analgesic effect of conditioned pain modulation (CPM; ie, pain inhibits pain phenomenon)^15,49 by music⁹ rather suggests a possible interference over some descending pain regulatory processes. In the study of Soyeux and Marchand,⁵⁶ the magnitude of music-induced analgesia was also correlated with the magnitude of CPM, tested separately in silence. These results suggest a possible competition or saturation of endogenous inhibitory processes when music and CPM are tested concurrently. On the other hand, another study found no effect of music on the temporal summation of pain or on CPM¹¹ so the specific conditions under which music-induced hypoalgesia interacts with mechanisms of central sensitization and descending inhibition remain to be determined.

Offset analgesia is another robust pain modulatory effect demonstrated experimentally by a large reduction in pain produced by a small and rapid decrease in the temperature of a highly painful heat stimulus.^31,33 Listening to one's favorite music has been found to reduce the magnitude of offset analgesia,¹¹ consistent with the principles of competition or saturation. However, the reduction in offset analgesia might also reflect the reduction in pain produced to the high intensity stimulus in the favorite music condition (ie, offset analgesia is reduced when the high stimulus intensity is less painful).³¹ Nevertheless, offset analgesia could also relate to reward-related brain mechanism triggered by relief onset in the ventral striatum.⁴ If confirmed, the reduction in offset analgesia by music may involve a saturation effect reflecting their shared dependency on reward-related processes.^10,18,55,62

4.3. Music, expectation, and anticipatory anxiety

Cognition and emotion are powerful modulators relying partly on descending processes, reward-related activity, and activation of the endogenous opioid and/or cannabinoid systems.^1,2,5,42,60 Previous research has demonstrated the role of affective processes and descending inhibition in music-induced analgesia,⁵³ but this is the first study that tested the impact of music on expectation-induced modulation. Both music and the audiobook condition partly blocked the hyperalgesic effect of high pain expectation.

The fear-avoidance model of pain suggests that high pain expectation increases anticipatory anxiety and produces hyperalgesia while optimism and positive affect may reduce pain.⁵⁹ Nocebo hyperalgesia also involves higher pain expectations and anticipatory anxiety.¹² A recent meta-analysis suggests that distraction techniques involving audiovisual stimuli can be effective in reducing fear and anxiety in clinical settings.³² Experimental studies indicate that expectation-induced pain modulation involves the up or downregulation of descending modulatory systems.^14,16,23 Two studies further demonstrated that a positive mood induced before hyperalgesia suggestions reduced the hyperalgesic response during the cold-pressor task²² and reduced the nocebo effect to a sham treatment.²¹ The same music and audiobooks used in the present study were previously tested in a clinical study in which participants consistently reported experiencing the music as more pleasant and relaxing than the audiobook.⁶ This is consistent with an affect-based explanation. However, the relatively small associations observed between the changes in pain and in anticipatory anxiety induced by music suggests that pain-related anxiety may not be the main explanation.

The possibility that the induction of positive affect reduces the impact of a subsequent aversive stimulus is not new,⁸ but our experimental design allowed testing the underlying psychological processes. According to the affect-based explanation, the positive affect induced by music should have no impact on the effects of hypoalgesic expectation or it may possibly improve it by reinforcing positive expectations, consistent with the reward-related explanation. In contrast, the present results show the opposite effect with the hypoalgesic effects of low pain expectations blocked to a comparable extent by music and the audiobook. A simple affect- or reward-based explanation is insufficient to account for the impact of music on expectation-induced pain modulation.

One alternative explanation is that auditory distraction interfered with the effects of expectations in both directions. Previous studies have shown that low pain expectations produce hypoalgesic effect in both experimental and clinical contexts.¹² It has been suggested that both music¹⁹ and expectations of analgesia¹⁷ independently result in a reduction of pain. However, some studies suggest that enhancing expectations of analgesia in the presence of music does not have an additive effect.³⁷ Our results further indicate a reduction in expectation-induced hypoalgesia while listening to music. This implies that auditory distraction might interfere with the processing of the anticipatory cue and/or the activation of expectation-related inhibitory processes. Taken together, this indicates that the modulation of pain by music and hypoalgesic expectations rely on partly separate mechanisms that may interfere with each other.

4.4. Potential clinical implications and limitations

The positive affect induced by music can help improve pain management.²⁴ Several meta-analyses support the benefits of music interventions on pain, anxiety, mood, quality of life, and/or satisfaction in diverse clinical contexts,⁵⁴ including aversive medical procedures in infants and children,⁵⁸ cancer,⁷ chronic pain,²⁰ and surgery or postoperative recovery.^35,41,43,44 However, these reviews highlight the need for methodological improvements. Nevertheless, most clinical studies involve between-subject designs and the large interindividual variability in uncontrolled factors including nociception, inflammation, and psychosocial contextual variables might introduce biases and reduce the sensitivity to clinical benefits, especially in small samples. The present findings relied on a sensitive within-subject design indicating a clear superiority of music over the audiobook control, as confirmed by very large effect sizes, but also demonstrating comparable large effect sizes of music and audiobook in reducing the effects of anticipatory processes producing hypoalgesia or hyperalgesia.

The ecological validity and generalizability of experimental approaches to study pain are admittedly limited, but they have the advantage of allowing for a precise control of the nociceptive stimulus, the individual differences in pain sensitivity, and the contextual factors known to modulate pain. The musical pieces and audiobooks used here were tested in our previous clinical study and provided highly consistent results showing the superiority of music over the audiobook for inducing relaxation and positive affect, and reducing the burden of care in dental implant surgery.⁶ Our translational approach suggests that the overall effect of music relies on several mechanisms including a nonspecific component involving interference with expectation-related processes.

5. Conclusion

The 2023 Global Year for Integrative Pain Care of the IASP (see https://www.iasp-pain.org/publications/iasp-news/the-iasp-2023-global-year-for-integrative-pain-care/) promotes new approaches to pain management. The present findings increase our understanding of the psychological processes that explain how music reduces pain and support further research on the use of standardized and personalized music interventions, such as that provided by the apps Music Care©, as a complementary method to optimize clinical care.

Importantly, music reduced the hyperalgesic effect of high pain expectations and the hypoalgesic effect of low pain expectations. This reinforces the importance of adopting a mechanistic approach to integrative pain care to highlight potential synergistic effects but also detect possible interference between psychological factors involved in pain management techniques.

Disclosures

No conflict to declare. A licence to use Music Care was provided free of charge to conduct the study. Stéphane Guétin, CEO of Music Care, participated in the early discussion on the research design and supported the study registration (https://osf.io/s98w7) and transparent reporting of the study. Pierre Rainville is a member of the Scientific Counsel of Music Care but receives no personal advantage, financial or otherwise, for this participation.

Supplemental digital content

Supplemental digital content associated with this article can be found online at http://links.lww.com/PR9/A331.