动物造模 z-bio 2022-04-28 326

　　Objective: To investigate the role of peripheral neuron protease-activated receptor 2-protein kinase A/protein kinase Cε (PAR2-PKA/PKCε) pathway in pain transformation, and to find a possible solution to simultaneously intervene in acute pain and chronic pain.

　　Methods: SD rats were randomly divided into blank group, sham-induced group, induced group, inhibitor 1 group and inhibitor 2 group. Except for the blank group and the sham-induced group, all rats were injected with carrageenan and prostaglandin E2 (PGE2) into the foot to establish a model of hyperalgesia induction. PGE2 was injected into the foot 7d after carrageenan injection. Rats in inhibitor 1 group and inhibitor 2 group were given PAR2 inhibitor before/after PGE2 injection. Observe the changes of mechanical pain thresholds (PWTs) of rats before injection, 5h, 3d, 6d, 7d0.5h, 7d4h and 7d24h after injection of carrageenan/saline, and detect the dorsal side of the model at 7d24h after carrageenan injection PAR2, protein kinase A (PKA) and protein kinase (PKCε) expression in root ganglia (DRG).

　　RESULTS: The pain sensitization induced model was successfully established. PGE2 administration 7d after carrageenan injection significantly prolonged the existence time of PGE2-induced pain. There was no significant difference in PWTs between the sham-induced group and the blank group at 7d and 24h after carrageenan injection (P>0.05). The PWTs of the rats in the induced group were significantly lower than those in the blank group and the sham induced group (P<0.01). The expressions of PAR2 and PKCε in the DRG on the modeling side of the rats in the induced group were significantly increased at 7d24h after carrageenan injection, which were higher than those in the sham-induced group and the blank group (P<0.05). PAR2 inhibition could significantly reverse the pain induced by PGE2 at 7d24h after carrageenan injection regardless of the time, and the pain induced by PGE2 in the induction group (P<0.05) was also inhibited, and the expression of PKCε in DRG was inhibited. However, administration of PAR2 inhibitors did not affect PGE2-induced acute pain and modulate PKA content in DRG.

　　Conclusion: Inhibition of PAR2 expression can block the transformation of acute pain to chronic pain, which may be related to the inhibition of PAR2-PKCε pathway activation in DRG. However, inhibition of PAR2 did not interfere with acute pain, which may be because PAR2-related pathways in DRG are not involved in the production of acute pain.