PAR2-PKA/PKCε z-bio 2021-02-02 305

　　bjective: To explore the role of peripheral neuroprotease activated receptor 2-protein kinase A/protein kinase Cε (PAR2-PKA/PKCε) pathway in pain changes, and possible solutions for simultaneous intervention in acute and chronic pain.

　　Method: The SD rats were randomly divided into blank group, sham induction group, induction group, inhibitor group 1 and inhibitor group 2. Carrageenan and prostaglandin E2 (PGE2) were injected into the paws of all rats except the blank group and the sham induction group to establish a hyperalgesia induction model. PGE 2 was injected into the foot 7 days after the carrageenan injection. Both inhibitor 1 and inhibitor 2 rats received the PAR2 inhibitor before and after the PGE2 injection. The changes in the mechanical pain threshold (PWT) of the rats were observed 0.5 hours, 3 days, 6 days, 7 days, 0.5 hours, 7 days, 4 hours and 7 days after injection of carrageenan/saline. The injection of model carrageenan PAR2, protein kinase A (PKA) and protein kinase (PKCε) 24 hours later the next day was expressed in the dorsal root ganglia (DRG).

　　Result: We successfully established a pain sensitization induction model. PGE2 administered 7 days after carrageenan injection can significantly prolong the occurrence of pain caused by PGE2. 7d24h after carrageenan injection, there was no significant difference in PWT between the sham-induced group and the blank group (P\→0.05). On the other hand, the PWT of the rats in the induction group was significantly lower than that of the rats in the blank group and the sham induction group (P\u003c0.01). 7d24h after carrageenan injection, the expressions of PAR2 and PKCε in the modeling side DRG of the induction group were significantly increased, and were higher than those of the sham induction group and the blank group (P\u003c0.05). At any time after the injection of carrageenan, the inhibitory effect of PAR2 was significantly reversed at 7d24h, induced PGE2-induced pain in the group of rats (P\u003c0.05), and inhibited the expression of PKCε in DRG. However, the administration of PAR2 inhibitors affected the acute pain induced by PGE 2, and could not regulate the PKA content of DRG.

　　 Conclusion: Inhibiting the expression of PAR2 can prevent the transition from acute pain to chronic pain. This may be related to the inhibition of the activation of the PAR2-PKCε pathway in DRG. However, inhibition of PAR2 cannot prevent acute pain. This may be because the PAR2-related pathway of DRG has nothing to do with acute pain.