Auditory Hyperresponsivity in Chronic Back Pain: A Randomized Controlled Trial of Pain Reprocessing Therapy

Ann Neurol. 2026 Feb 27. doi: 10.1002/ana.78183. Online ahead of print.

ABSTRACT

OBJECTIVE: Heightened sensitivity to noxious stimulation is a hallmark of chronic pain. Emerging evidence suggests heightened unpleasantness to non-noxious (eg, auditory) aversive stimulation also characterizes chronic pain, but its magnitude, neural mechanisms, and treatment modifiability remain unknown.

METHODS: We compared behavioral and neural responses to auditory and pressure stimulation in 142 adults with chronic back pain (CBP) relative to 51 pain-free controls. CBP patients then entered a randomized trial of pain reprocessing therapy (PRT) versus placebo and usual care. During functional magnetic resonance imaging, participants experienced low- and high-intensity aversive sounds and mechanical pressure and provided unpleasantness ratings. Univariate analyses examined responses in primary sensory, sensory-integrative, and midline default mode network regions. Multivariate analyses tested 4 a priori whole-brain patterns, including patterns predictive of fibromyalgia.

RESULTS: CBP patients versus healthy controls reported heightened unpleasantness to auditory stimuli (Hedges' g = 0.95-1.03; p < 0.001) and mechanical pressure (g = 0.49-0.66; p < 0.001). For patients versus controls, auditory stimulation revealed hyperresponsivity in primary auditory cortex and insula, hyporesponsivity in the precuneus and medial prefrontal cortex (g = 0.33-0.59, p < 0.05), and increased expression of generalized and auditory-specific aversive processing patterns (g = 0.33-0.39, p < 0.05) and of fibromyalgia-derived multisensory sensitivity patterns (g = 0.43-0.50, p < 0.01). Longitudinal analysis found that PRT versus placebo led to reduced unpleasantness of low-intensity auditory stimulation, along with increased medial prefrontal cortex responses for PRT versus usual care.

INTERPRETATION: CBP is associated with pronounced auditory hyperresponsivity via modality-specific and modality-general neural pathways, and brain mechanisms overlap with fibromyalgia. PRT versus control produced small reductions in this hyperresponsivity, suggesting potential for PRT to yield broader "central desensitization". ANN NEUROL 2026.

PMID:41761046 | DOI:10.1002/ana.78183