Ethanol Increases Mechanical Pain Sensitivity in Rats via Activation of GABAA Receptors in Medial Prefrontal Cortex

Ethanol is widely known for its ability to cause dramatic changes in emotion, social cognition, and behavior following systemic administration in humans.Human neuroimaging studies suggest that alcohol dependence and chronic pain may share common mechanisms through amygdala-medial prefrontal cortex(m PFC) interactions. However, whether acute administration of ethanol in the m PFC can modulate pain perception is unknown.Here we showed that bilateral microinjections of ethanol into the prelimbic and infralimbic areas of the m PFC lowered the bilateral mechanical pain threshold for 48 h without influencing thermal pain sensitivity in adult rats.However, bilateral microinjections of artificial cerebrospinal fluid into the m PFC or bilateral microinjections of ethanol into the dorsolateral PFC(also termed as motor cortex area 1 in Paxinos and Watson’s atlas of The Rat Brain. Elsevier Academic Press, Amsterdam, 2005) failed to do so, suggesting regional selectivity of the effects of ethanol. Moreover, bilateral microinjections of ethanol didnot change the expression of either pro-apoptotic(caspase-3 and Bax) or anti-apoptotic(Bcl-2) proteins, suggesting that the dose was safe and validating the method used in the current study. To determine whether c-aminobutyric acid A(GABA) receptors are involved in mediating the ethanol effects, muscimol, a selective GABAreceptor agonist, or bicuculline, a selective GABAreceptor antagonist, was administered alone or co-administered with ethanol through the same route into the bilateral m PFC. The results showed that muscimol mimicked the effects of ethanol while bicuculline completely reversed the effects of ethanol and muscimol. In conclusion, ethanol increases mechanical pain sensitivity through activation of GABAreceptors in the m PFC of rats.