Pain-related aversion induces astrocytic reaction and proinflammatory cytokine expression in the anterior cingulate cortex in rats

Pain involves sensory and affective dimensions. It is well-known that activation of glial cells and a subsequent increase in proinflammatory cytokines contribute to the pathogenesis of pain sensation. However, the role of glial cells and proinflammatory cytokines in pain affect is unclear. Several lines of evidence indicate that the anterior cingulate cortex (ACC) is a key structure for pain affect. Using the formalin-induced conditioned place avoidance (F-CPA) model, which reflects the pain-related negative affective state induced by nociceptive stimuli, we examined the mRNA and protein expression levels of astrocytic markers and proinflammatory cytokines in the ACC. F-CPA produced robust aversion-like behaviors in rats. In parallel, a significant increase of mRNA of astrocytic markers (GFAP and S100B), and proinflammatory cytokines (IL-1β and TNF-α) were observed in the ACC. The protein level of GFAP, IL-1β and TNF-α were also enhanced in the ACC. The results showed for the first time that astrocytes and proinflammatory cytokines are associated with the processing of pain-related aversion and may be crucial players in the affective dimension of pain in rats.