Persistent neuropathic pain selectively impairs hedonic and motivational aspects of eating: Insights from a mouse...

Chronic pain is known to disrupt affective and motivational states, yet its impact on eating behavior-particularly the balance between homeostatic and reward-driven intake-remains poorly understood. Using the spared nerve injury (SNI) model in male and female mice, we investigated how persistent neuropathic pain alters food intake and reward processing. Fourteen days post-surgery, mice underwent a binge-eating protocol with high-fat diet (HFD), along with operant conditioning for chocolate pellets, and a sucrose preference test to assess hedonic and motivational behavior. Chow intake and body weight were tracked to monitor homeostatic feeding. SNI induced mechanical hypersensitivity without affecting daily chow intake or weight, indicating preserved homeostatic feeding. In contrast, male SNI mice showed an attenuated and irregular escalation of HFD consumption, reduced operant responding and sucrose preference-consistent with diminished motivation and anhedonia. Female SNI mice exhibited similar motivational impairments but did not show a clear binge-like eating phenotype. To explore underlying mechanisms, we assessed neuronal activation in nucleus accumbens (Acb) subregions-a key site where pain and reward pathways converge-using c-Fos immunostaining following HFD exposure. While HFD increased c-Fos expression in both control and SNI groups, no significant differences were detected between them, suggesting that pain-induced changes in hedonic feeding may involve non-canonical neural circuits or mechanisms not captured by immediate early gene activation. Together, these results indicate that persistent neuropathic pain selectively disrupts hedonic and motivational aspects of eating behavior, while sparing homeostatic regulation, and may signal the emergence of broader affective disturbances associated with chronic pain. PERSPECTIVE: This article presents data from mouse models combining neuropathic pain and binge-eating paradigms, revealing that persistent pain selectively disrupts specific components of eating behavior-insights that may help inform strategies to prevent comorbid eating disorders in chronic pain patients.