Papers of the Week

Alcohol use disorder (AUD) and chronic pain are complex and debilitating conditions that are difficult to treat, lead to enormous economic costs, and excessive suffering. The difficulty in developing new treatments for AUD is partially due to the lack of consideration given to the wide array of factors that drive alcohol intake. Clinical data suggest that both men and women with chronic pain are more likely to develop alcohol use disorder and report using alcohol to deal with chronic pain. Additionally, it has been shown that self-report of chronic pain correlates with alcohol relapse after a period of abstinence. These data led to the hypothesis that neural mechanisms that contribute to alcohol related behaviors are different in individuals that are also experiencing chronic pain. To test this hypothesis, we used a conditioned place preference (CPP) paradigm to model ethanol seeking in male and female rodents that had undergone either a spared nerve injury (SNI) model of chronic pain or a sham surgery. To determine a dose of ethanol that may be selectively rewarding to injured animals, we first tested the analgesic effects of multiple doses of ethanol on pain-related behaviors in SNI and Sham mice. The higher doses of 1.0g/kg and 2.0g/kg (i.p.) of ethanol were anti-allodynic in SNI mice and analgesic in sham mice. However, we found that the lower dose 0.5 g/kg of ethanol was able to fully reverse mechanical hypersensitivity in SNI animals, while not influencing mechanical thresholds in sham mice. Thus, we conditioned mice using 0.5g/kg of ethanol. We found this dose induced a modest conditioned place preference for the ethanol-paired chamber in both SNI and Sham male mice. Mice then underwent extinction training for 1 week, during which time animals were exposed to the CPP apparatus without receiving any ethanol. To investigate relapse-related behavior, we then tested whether painful stimulation would reinstate ethanol seeking behavior. We found that threshold hindpaw stimulation was able to reinstate ethanol seeking behavior in SNI, but not sham animals. This suggests that animals in chronic pain may associate alcohol with pain relief or that chronic pain animals may be more sensitive to stress induced reinstatement when pain is the stressor. We also tested the effect of drug induced reinstatement and found no differences between SNI and Sham mice, leading us to believe that differences found in pain induced reinstatement were selective to that modality. Ongoing work is aimed at determining the effect of ethanol on weight bearing behavior as well as the effect of chronic pain on ethanol seeking and relapse-related behavior in female mice.