Figure 6.

Adaptations in CeA-PAG circuitry contribute to hyperalgesia following alcohol dependence. Left, Schematic depicting CeA-PAG circuitry under baseline conditions. CeA GABAergic neurons project to PAG, ultimately resulting in disinhibition of MOR-containing PAG neurons, initiating the descending pain inhibition pathway. Right, Following repeated cycles of alcohol exposure and withdrawal, MC4R expression is decreased in the CeA. There is a decrease in the strength of CeA projections to PAG, resulting in increased inhibition of PAG output neurons to RVM and/or forebrain regions (e.g., TH⁺ projections to BNST) and/or midbrain regions (e.g., VTA/SN). Ultimately, these adaptations contribute to dependence-induced hyperalgesia. Illustration generated by modifying images purchased in the Illustration Toolkit-Neuroscience from Motifolio.