The term “centralized pain” describes any central nervous system (CNS) dysfunction or pathology that may contribute to the development or maintenance of chronic pain (1–3). There is a growing appreciation of the role of CNS augmentation in pain processing in many chronic pain conditions (2, 4). A hallmark of the centralized pain phenotype is the presence of hyperalgesia and reduced or absence of endogenous analgesia (5–7). Data from quantitative sensory testing (QST) studies suggest a wide, bell-shaped distribution in pain sensitivity across the general population. Most individuals with centralized pain fall on the right side of this curve and have QST findings consistent with hypersensitivity (hyperalgesia and allodynia) (1, 8–13). QST evidence of widespread hypersensitivity is consistently observed in many chronic pain conditions, including FM, irritable bowel syndrome, tension headache, low back pain, temporomandibular joint disorder, interstitial cystitis, and vulvodynia (14–23). Widespread hypersensitivity is often measured through QST sensitivity testing of pain to pressure on the thumbnail bed. As evidence suggests, temporal summation, which is the phenomenon of amplifying pain perception after being subjected to repeated or continuous noxious stimulation, despite having the same intensity of the stimulus (24), is an essential role player in FM (25, 26). Therefore, in this study, we used QST to objectively measure pain sensitivity and temporal summation while listening to music compared to listening to nature sounds in patients with FM.

Music has been previously shown to influence parameters of the autonomic nervous system associated with anxiety (27), such as slowing heart rate (28) and respiration (29). Music listening can also reduce acute pain during surgery (30), post-operative recovery (31), orthodontic procedures (32), orthopedic rehabilitation (33), and during thermic pain induction in healthy participants (34, 35). The subjective analgesic, anxiolytic, and antidepressant effects of music for people with chronic pain were recently confirmed in a meta-analysis (36). However, the impact of music listening on objective measures of pain sensitivity in patients with chronic pain has not yet been described. The goal of this pilot study was to understand the possible analgesic effects of music listening on objective measures of pain sensitivity in patients with fibromyalgia (FM).

The analgesic effect of music is thought to occur through several mechanisms: Contextual, Cognitive, Emotional, and Physiological (37, 38). First, music provides a predictable context that can increase the listeners' sense of control. This is further enhanced if the music is familiar, as this can bring in other effects that are not related to aspects of music specifically, such as setting up expectations and heightening nostalgia. Studies have shown the greatest analgesic effects when music is selected by participants. Second, similar to other types of stimulation, such as reading or listening to nature sounds (39), music can serve as a cognitive distraction and take attention away from the painful stimulus. Third, music is a powerful inducer of emotion (40, 41). Music that is positive, liked by the listener, and low on arousal has the strongest analgesic effect (34). Finally, music listening interventions and music therapy have also been shown to reduce anxiety and depression (42, 43). The anxiolytic effect may be due to the physiological effect of music on the parasympathetic nervous system, increasing the vagal response and reducing heart rate and respiration rate (27). Music also has effects on the brain directly, causing the release of endogenous opioids and dopamine and activating the areas of the descending pain modulatory system (44, 45). The specific musical characteristics that yield the greatest analgesic effects are difficult to pinpoint, as there is no standard for reporting. Meta-analyses have revealed that music with 60–80 beats per minute, in a major key, and without lyrics or percussion has the largest effects (46).

Previous studies in patients with FM have shown that patients have reduced self-reported pain and increased mobility after even a short, 10-min music listening intervention. After listening to the music of their choice, participants were faster in a standard mobility assessment, that is, the timed-up-and-go task (47). A second study using resting-state functional magnetic resonance imaging confirmed the impact of 5-min music listening intervention on the centralized descending pain modulatory system (DPMS), identified as changes in functional connectivity between regions of the DPMS that positively correlated with changes in pain scores (48). To our knowledge, this is the first study to investigate whether objectively measured pain sensitivity is reduced by music listening in patients with FM.

The goal of the current study was to identify whether music listening has a promising analgesic effect during pain threshold and tolerance testing for patients with FM that supersedes any effect of auditory distraction. We used standardized music, rather than music selected by the participants, so that we could determine whether the specific music characteristics described above (i.e., slow tempo, consonant harmonies, no lyrics, or percussion) would be sufficient to elicit an analgesic effect. While a personalized choice might elicit a greater effect, it would not be possible to determine whether the effect was due to the music characteristics or from the person's previous associations and memories with that music. We hypothesized that because the nature listening condition provides a distraction from pain sensations, and may also provide some of the same Contextual, Cognitive, Emotional, and Physiological impacts as music, both listening conditions (Music and Nature) would reduce pain sensitivity compared to testing during silence. However, as noted previously, the emotional and physiological impacts are anticipated to be stronger in music due, in part, to temporal structure and expectancy building. Therefore, we hypothesized that music listening would reduce pain sensitivity compared to nature sounds. We further hypothesized that music would increase vagal input to the autonomic nervous system, decreasing heart rate and increasing heart rate variability compared to both silence and nature sounds, and that analgesic responsiveness would be moderated by symptoms of FM, anxiety, and depression.

In this pilot study, we measured the analgesic effects associated with music and nature sounds on objective autonomic system responsiveness to painful stimuli. Our experimental design allowed for blinding during both data collection and analysis, reducing the potential for bias. By counterbalancing the order of audio presentation, we showed the feasibility of repeated measures testing in patients with FM while controlling for order effects. Even in our small sample, randomization successfully yielded relatively matched groups, with no group differences observed for FM symptoms, age, marital status, or education. By random chance, we did observe between-group differences in anxiety, although the Nature group was numerically only seven points higher than the Music group, and both groups were within one standard deviation of the standardized mean on the PROMIS scale.

This study is limited by the small sample size, and the results should be interpreted with caution. Due to the small sample size, it was difficult to fully balance the groups. Our groups differed on anxiety potentially confounding our results, although all participants were in the mild to moderate anxiety range. Additionally, although it was not statistically significant, more participants in the Music group had attained education beyond a bachelor's degree. However, inherently when having a small sample size, it is somewhat easier to detect within-participant effects rather than between-participant effects. It is possible that a greater analgesic effect would be elicited from the music of an individual's choice, as that could potentially have greater associations with positive memories and previous experience, thus enhancing the physiological response. Our experimental design using nature sounds as an auditory control and carefully selected musical selections with characteristics hypothesized to facilitate relaxation and analgesia is a strength, and can be used in future studies to separate the effects of auditory distraction from music-specific effects.

In conclusion, our current results did not support our hypothesis of stronger analgesic effects of music vs. distracting nature sounds; however, we did observe strong effects of auditory distraction on pain temporal summation and tolerance. The confounding effect of anxiety symptoms in our study, as well as the individual differences observed on the MEQ, suggest that variability in mood and other factors may be important in understanding how individuals will respond to music or other auditory stimuli to gain therapeutic analgesic effects. While these results should be treated with caution, this study provides preliminary evidence that some individuals may benefit from music or audio stimulation as a treatment more than others. Further study is warranted.

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: https://osf.io/84baz.

The studies involving human participants were reviewed and approved by University of Kansas Medical Center Institutional Review Board Human Subjects Committee. The patients/participants provided their written informed consent to participate in this study.

RL: conceptualization, methodology, formal analysis, investigation, data curation, writing of the original draft, project administration, and funding acquisition. MM: formal analysis, investigation, data curation, reviewing and editing, and project administration. AC: conceptualization, methodology, resources, writing of the original draft, reviewing and editing, and funding acquisition. ZM: reviewing and editing. LM: resources and reviewing and editing. KG: conceptualization, methodology, investigation, resources, and reviewing and editing. All authors contributed to the article and approved the submitted version.

This study was funded by the National Institutes of Health through a KUMC Frontiers Arts+Medicine Trailblazer to RL (NIH UL1TR002366), NIH K23GM123320 to AC, and by the KUMC Hoglund Biomedical Imaging Center (HBIC Neurophysiology Core and Cognitive Neuroscience Unit). The Hoglund Biomedical Imaging Center is supported by a generous gift from Forrest and Sally Hoglund and funding from the National Institutes of Health including: UL1 TR002366: Frontiers: KU Institute for Clinical & Translational Science, and a KUMC Equipment Grant.

AC serves as a consultant for Swing Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.