Rac2 enhances activation of microglia and astrocytes, inflammatory response, and apoptosis via activating JNK signaling pathway and suppressing SIRT1 expression in chronic constriction injury-induced neuropathic pain.

Neuropathic pain (NP) is pain caused by injury or dysfunction of the somatosensory system. The role of Rac2, a member of the Rac family, which is expressed in neutrophils, macrophages, and adult T cells, in NP remains unclear. Using a chronic constriction injury (CCI)-induced NP model in rats, we found that Rac2 expression was elevated in rats with CCI-induced NP and that overexpression of Rac2 aggravated the NP. Rac2 overexpression also aggravated the inflammatory response, induced activation of microglia and astrocytes, and enhanced apoptosis whereas knockdown of Rac2 had the opposite effects. Rac2 suppressed SIRT1 expression via activating the c-Jun N-terminal kinase (JNK) signaling pathway. In rescue experiments, SRT1720, an activator of SIRT1, reversed the effect of Rac2 on glial activation, inflammatory response, and apoptosis. These findings indicate that Rac2 enhances the activation of microglia and astrocytes, inflammatory response, and apoptosis via activating the JNK signaling pathway and suppressing SIRT1 expression in CCI-induced NP.