Peri-adolescent ethanol exposure differentially affects mechanical and thermal sensitivity in rats

Chronic pain is exacerbated in individuals with alcohol use disorder (AUD) and often difficult to manage. Binge levels of ethanol intake during adolescence promotes AUD and comorbid chronic pain in adulthood. We and others have consistently reported adolescent ethanol exposure-associated augmentation in mechanical sensitivity during protracted abstinence in murine models. However, to date the effect of adolescent ethanol exposure on thermal hyperalgesia are mixed and dependent on sex and abstinence time. In this project we exposed Long Evans rats to air or ethanol intermittently throughout the peri-adolescent period (PD 28-68) and assessed mechanical sensitivity and thermal nociception weekly from Week 1 - 4 of abstinence. We observed baseline sex differences in mechanical allodynia and thermal hyperalgesia whereby air-exposed female rats exhibited greater sensitivity than the age-matched male rats. Furthermore, while ethanol exposure augmented mechanical sensitivity in both sexes, response to thermal nociception was specific to male rats. Our assessment of fear conditioning during protracted abstinence (Week 6) using a three-day context-dependent procedure revealed basal sex-differences whereby air-exposed female rats demonstrated lower retention of fear memory than male rats, but no aCIE exposure-associated changes in unconditioned or conditioned freezing in either sex. Together these results suggest that adolescent ethanol exposure-associated pain sensitivity varied depending on sex and pain modality. Importantly, enhanced pain sensitivity did not generalize to unconditioned or conditioned fear responses, and were not driven by differences in aversion-based learning. PERSPECTIVE: This article characterizes pain sensitivity in a rat model of adolescent alcohol exposure, overall suggesting that adolescent alcohol exposure potentiated pain sensitivity in adulthood. This model can be used in future studies to develop evidence-based pharmacotherapies to treat chronic pain in individuals with a history of high levels of alcohol misuse.