Spared nerve injury decreases motivation in long-access homecage-based operant tasks in mice

Abstract

Neuropathic pain causes both sensory and emotional maladaptation. Preclinical animal studies of neuropathic pain-induced negative affect could result in novel insights into the mechanisms of chronic pain. Modeling pain–induced negative affect, however, is variable across research groups and conditions. The same injury may or may not produce robust negative affective behavioral responses across different species, strains, and laboratories. Here, we sought to identify negative affective consequences of the spared nerve injury model on C57BL/6J male and female mice. We found no significant effect of spared nerve injury across a variety of approach-avoidance conflict, hedonic choice, and coping strategy assays. We hypothesized these inconsistencies may stem in part from the short test duration of these assays. To test this hypothesis, we used the homecage-based Feeding Experimentation Device version 3 to conduct 12-hour, overnight progressive ratio testing to determine whether mice with chronic spared nerve injury had decreased motivation to earn palatable food rewards. Our data demonstrate that despite equivalent task learning, spared nerve injury mice are less motivated to work for a sugar pellet than sham controls. Furthermore, when we normalized behavioral responses across all the behavioral assays we tested, we found that a combined normalized behavioral score is predictive of injury state and significantly correlates with mechanical thresholds. Together, these results suggest that homecage-based operant behaviors provide a useful platform for modeling nerve injury-induced negative affect and that valuable pain-related information can arise from agglomerative data analyses across behavioral assays—even when individual inferential statistics do not demonstrate significant mean differences.

Effect of Pain in the Development of Alcohol Use Disorders: Ethanol-evoked Dopamine Release Alterations in the Rat Nucleus Accumbens

“…Clinical studies lay bare a connection between pain suffering and alcohol use disorders (AUDs); (Apkarian et al, 2013;Jakubczyk et al, 2016) probably because pain induces alterations in the function of overlapping brain areas (Schrepf et al, 2016;Liu et al, 2022;Jiang et al, 2023). Diverse types of pain conditions alter basal ganglia structure and anatomy, and negatively impact motivation and reward processing, which triggers stress and negative affect states (Schwartz et Norris et al, 2024). In the basal ganglia, the Ventral Tegmental Area -Nucleus Accumbens connexion (VTA -NAc), a pathway with numerous dopaminergic neurons, plays a pivotal role in AUDs (Deehan et al, 2013).…”