Chronic pain selectively reduces the motivation to work for remifentanil but not food reward.

Abstract

Currently, preclinical research has reported conflicting evidence as to whether chronic pain imparts resilience or vulnerability to opioid drug seeking. Here, we investigated the impact of chronic pain on the intravenous self-administration (IVSA) profile of the short-acting opioid analgesic remifentanil in a mouse model. Using a chronic constriction injury model of chronic neuropathic pain, 7 days after injury, male and female C57Bl/6J mice began remifentanil IVSA. During the acquisition phase, there were no differences in the total number of reinforcers earned but an increase in the number of active nose pokes in pain mice. An increase in the rate of acquisition within sessions was observed in male but not female mice. When work effort increased (fixed ratio 3 and progressive ratio), pain mice unexpectedly showed a reduction in the number of reinforcers earned and their breakpoint. This change in motivational state was specific to the willingness to work for remifentanil, as these changes were not observed with higher effort for a food reward. We hypothesized that chronic pain altered the dopaminergic state of the striatum, which would impact the motivation to work for a reward. We found that pain mice had significantly decreased phasic dopamine release assessed via fast-scan cyclic voltammetry and reduced potassium-evoked extracellular dopamine measured by microdialysis. Future studies will investigate the causal relationship between this hypo-dopaminergic state and decreased behavioral motivation associated with a chronic pain state.