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Objective To investigate the analgesia effect of HS014 on the neuropathic pain rat and effect of HS014 on the astrocyte activaion and proinflammatory cytokine expression in the periaqueductal gray induced by CCI. Methods 75 mature male wistar rats were randomly divided into 3 groups:Group A (sham,n=25), Group B (CCI+saline, n=25), which received sciatic nerve ligation, the same volume saline with group C was administered PAG 1h before surgery and continued daily to day 14 post-operation. Group C (CCI+HS014, n=25), which received sciatic nerve ligation, HS014 (the volume of HS014 was 5ug/0.5ul) was administered PAG 1h before surgery and continued daily to day 14 post-operation. The pain-related behavior, Paw withdrawal threshold (PWT) changes in properation (d0) and post-operative 1,3,7,14 days were assessed. After the pain-related behavior assess, the rats PAG were removed. The immunohistology of glial fibrillary acid protein (GFAP) and proinflammatory cytokine and the change of their expressions in 3 groups at different timepionts were analyzed and compared. Results Sham group(Group A) rats produced no significant behavioral hypersensitivity and showed less expression of GFAP,α-TNF, IL-1βimmunohistology after operation compared with preoperation(P>0.05). The PWT of ipsilateral lower limb in Group B,C rats after CCI shorted compared with those of pre-ligation at postoperative 1,3,7,14 days (P<0.05或P<0.01). After CCI, theα-TNF and IL-1βimmunohistology at PAG increased significantly compared with preoperative at postoperative 1,3,7,14 days (P<0.05或P<0.01). Mean optical density of GFAP at PAG in group B,C rats increased significantly compared with preoperative at postoperative 3,7,14 days(P<0.05或P<0.01). Conversely, preemptive treatment of HS014(Group C) reduced the hyperalgesia, suppressed mean optical density of GFAP and alleviatedα-TNF, IL-1βexpression(P<0.05或P<0.01) in Group C compared with Group B among observing timepionts. Conclusion Robust astrocytes activation and proinflammatory cytokine overexpression was observed at PAG in rodent models of chronic pain, in which GFAP,α-TNF,IL-1βsimultaneously increasing paralled with the level of hyperalgesia. Preemptive treatment of HS014 suppressed robust astrocytes activation and proinflammatory cytokine overexpression, more significantly alleviated the development of the behavior hypersensitivity in the rat model of neuropathic pain.
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