动物造模,痛转化模型 z-bio 2021-09-15 216

　　OBJECTIVE: To discuss the role of peripheral neuronal protease-activated receptor 2-protein kinase A/protein kinase Cε (PAR2-PKA/PKCε) pathway in the transformation of pain, and to find possible plans for simultaneous intervention in acute pain and chronic pain.

　　Method: SD rats were randomly divided into blank group, sham induction group, induction 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) to establish a hyperalgesia induction model. PGE2 was injected into the foot 7 days after the carrageenan injection. Rats in inhibitor 1 group and inhibitor 2 group were given PAR2 inhibitor before/after PGE2 injection. Observe the changes in the mechanical pain threshold (PWTs) of rats before injection, 5h, 3d, 6d, 7d0.5h, 7d4h and 7d24h after injection of carrageenan/physiological saline, and detect the side dorsal of the modelling at 7d24h after carrageenan injection PAR2, protein kinase A (PKA) and protein kinase (PKCε) are expressed in root ganglia (DRG).

　　Result: Pain sensitization induces a successful model establishment. PGE2 was given 7 days after carrageenan injection, which significantly prolonged the existence time of PGE2 induced pain. There was no significant difference in PWTs of rats in the pseudo-induced group 7d24h after carrageenan injection and the blank group at the same time (P>0.05). The PWTs of rats in the induction group were significantly lower than those in the blank group and pseudo-induction group during the same period (P＜0.01). The expressions of PAR2 and PKCε in the DRG on the modeling side of the induced group increased significantly at 7d24h after carrageenan injection, which was higher than that of the sham-induced group and the blank group during the same period (P<0.05). Inhibition of PAR2, regardless of time, can significantly reverse the 7d24h after carrageenan injection, induce the pain induced by PGE2 in rats in the group (P<0.05), and inhibit the expression of PKCε in DRG. However, the administration of PAR2 inhibitors could not affect the acute pain induced by PGE2 and modulate the PKA content in DRG.

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