Dexmedetomidine inhibits visceral pain via suppression of PKCγ and JAK2/STAT3 signaling pathways

Objective: Dexmedetomidine (DEX) served as an anesthetic for a long time. This study was directed toward probing into its antalgic effects on acute inflammatory visceral pain (AIVP) elicited by trinitrobenzene sulfonic acid (TNBS) and to assess if DEX's antinociceptive effects were mediated by PKC gamma or JAK2-STAT3 signaling pathways. Methods: TNBS induction was performed in rats to establish AIVP model. Abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL) were measured to examine the pain behavior of rat model. Results: Western blot (WB), real-time PCR and cellular fractionation assays were also conducted. In mDEX and hDEX groups, the AWR score was significantly reduced (P < 0.01), while TWL and MWT values were dramatically increased (P < 0.05) compared with those in AIVP group. Moderate to high DEX dosages inhibited the release of pro-inflammatory cytokines, like IL-1 beta, IL-6, TNF-alpha, and PGE2, and stimulated the release of IL-2. WB and real-time PCR revealed that mDEX and hDEX administration inhibited PKC. and JAK2/STAT3 at both the protein and mRNA levels. Moreover, PKC. and JAK2/STAT3 were dephosphorylated by mDEX and hDEX treatment. We found that PKC. was translocated to the membrane, while JAK2 and STAT3 were mainly located in the nucleus after DEX treatment (DEXT). Conclusion: Taken together, we conclude that DEX's analgesic effect in AIVP is modulated by PKC. inhibition and JAK2/STAT3 signaling pathways.