Adults with chronic back pain rated aversive sounds as substantially more unpleasant than pain-free controls, with larger effect sizes than those observed for mechanical pressure pain, according to a randomized controlled trial published in Annals of Neurology.
The findings, from a community sample of 142 adults with chronic back pain (CBP) and 51 matched controls, extend prior multisensory sensitivity research—which has focused largely on fibromyalgia—to an unselected, high-functioning CBP population and provide the first evidence that auditory hyperresponsivity in chronic pain may be partially modifiable with psychological treatment.
Study Design and Population
Data were drawn from a clinical trial (NCT03294148) conducted at the University of Colorado Boulder between August 2017 and November 2018. Participants with CBP were community-recruited adults aged 21–70 years who reported ongoing back pain on at least half the days of the preceding 6 months, with a last-week average pain intensity score of 4 or higher on a 0–10 scale.
Exclusion criteria included inflammatory disorders, metastasizing cancer, unexplained significant weight loss, neurological abnormalities, or leg pain exceeding back pain, yielding a sample of predominantly primary (centralized) CBP.
Control participants had no history of chronic pain and were matched on age and sex. The CBP and control groups were comparable on socioeconomic status, education, and exercise habits, although racial composition differed between groups.
Patients with CBP were randomized 1:1:1—balanced on age, sex, baseline pain, and opioid use—to pain reprocessing therapy (PRT), open-label placebo (subcutaneous saline injection), or usual care. PRT consisted of one physician telehealth session and eight psychological sessions delivered over 4 weeks and aimed to help patients reconceptualize pain as arising from non-dangerous brain activity rather than tissue injury.
Stimulation Paradigm
During functional magnetic resonance imaging, participants received pressure pain and aversive sound stimuli at low and high intensities and rated unpleasantness after each exposure on a 0–100 visual analog scale.
Neuroimaging analyses targeted three hierarchical levels: primary sensory regions (including primary auditory cortex and somatosensory cortex), sensory-integrative pathways (insula subregions), and midline default mode network areas (including medial prefrontal cortex and precuneus). Multivariate analyses also assessed previously validated negative affect and fibromyalgia-related whole-brain patterns.
Cross-Sectional Behavioral Results
Patients with CBP reported significantly greater unpleasantness than controls for both modalities. Group differences were larger for auditory stimulation (Hedges g approximately 1.0) than for mechanical pressure (g approximately 0.5 to 0.6), indicating stronger cross-modal amplification for sound than for pain-specific pressure input.
No group-by-intensity interaction was detected, indicating that patients and controls encoded increasing stimulus intensity similarly but differed in baseline responsivity.
Among patients with CBP, greater back pain severity was associated with higher unpleasantness ratings at both intensity levels, particularly for auditory stimuli.
Neuroimaging Findings
Primary Sensory Regions
Patients with CBP showed significantly greater A1 responses during auditory stimulation compared with controls, with moderate effect sizes (Hedges g approximately 0.4 to 0.7 across intensities).
No significant group differences were observed in subcortical auditory relays or in primary somatosensory cortex during pressure stimulation.
Insula
All three insula subregions showed significantly greater activation in patients with CBP compared with controls during auditory—but not pressure—stimulation, with small-to-moderate effect sizes (g approximately 0.3 to 0.5).
Dorsal-anterior insula responses positively correlated with patients’ average clinical pain during the prior week.
Default Mode Network
Midline default mode network regions, including the medial prefrontal cortex (mPFC) and precuneus, showed reduced activation in CBP during auditory stimulation. Effect sizes were small to moderate (g approximately 0.2 to 0.6). mPFC activity during low-intensity auditory stimulation correlated with spontaneous in-scanner back pain ratings. No significant group differences were observed in these regions during pressure stimulation.
Multivariate Pattern Analyses
During auditory stimulation, patients with CBP showed greater expression of both the auditory-specific and generalized negative affect patterns (g approximately 0.3 to 0.4), as well as fibromyalgia-derived multisensory sensitivity patterns (g approximately 0.5). These differences were not observed during pressure stimulation.
Longitudinal Treatment Effects
PRT significantly reduced auditory unpleasantness compared with placebo for low-intensity sounds, with similar trends at high intensity and versus usual care.
Mixed-effects modeling revealed a significant increase in mPFC responses over time in the PRT group compared with usual care, consistent with partial normalization of baseline default mode network hyporesponsivity. No significant mPFC difference was observed for PRT versus placebo.
Whole-brain voxelwise analyses largely confirmed patterns of auditory cortex and insula hyperactivation and DMN hypoactivation during auditory stimulation.
Limitations
Within-person trial counts were relatively low, limiting measurement reliability. The CBP and control samples differed in racial composition, underscoring the need for more diverse populations.
Methodological variability in mechanical stimulation—such as thumb size or possible repositioning during scanning—may have contributed to weaker pressure findings compared with the standardized auditory paradigm. Treatment effects were modest, and missing data patterns may have influenced longitudinal results.
Interpretation
“These findings imply that sensory amplification is not an immutable trait, but a dynamic and reversible process,” the authors wrote.
The study found that pain reprocessing therapy was associated with reductions in auditory unpleasantness and changes in mPFC activity, indicating that auditory hyperresponsivity in CBP may be treatment-responsive.
Disclosures can be found in the study.
Source: Annals of Neurology