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

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 20269999:n/a-n/a.