Activation Of Extracelluar Signal-Regulated Kinase In Dorsal Horn Induced By Incision In Rats And The Effect Of Parecoxib

OBJECTIVE:The current study aims to explore the role of ERK in spinal cord in incisional pain and the effect of parecoxib on the expression of spinal ERK after surgical incision.METHODS:Rats were received one hind paw incision; pERK1/2(p44/42) in spinal cord was measured by immunohistochemistry. ERK inhibitor, U0126(1μg) was intrathecally injected20min before incision or20min after incision. Parecoxib was intraperitoneally injected (6mg/kg)20min before or after incision. Pain hypersensitivity was evaluated by von Frey test. Brushing (innocuous stimulus) was used to explore its effect on ERK activation under the pain state induced by incision.RESULTS:The ERK of ipsilateral L4-L5spinal superficial dorsal horn (lamina Ⅰ and Ⅱ) was activated at lmin immediately after hind-paw incision in rats, followed by reaching a peak at5min, and then returned to basal level thereafter. Pretreatment with U0126dramatically attenuated the mechanical pain hypersensitivity induced by hind paw incision. However, U0126post-treatment had only marginal effect on incision-evoked mechanical pain hypersensitivity. COX-2inhibitor parecoxib suppressed the transient activation of spinal p-ERK and mechanical pain hypersensitivity. However, pretreatment of COX-2inhibitor had more potent analgesic effect than post-treatment. Additionally, brushing the edge of incised skin at10min after hind-paw incision could markedly increase the expression of p-ERK again which could be attenuated by COX-2inhibitor. CONCLUSIONS:ERK activation in spinal dorsal horn play an important role in the development of pain hypersensitivity induced by surgical incision. The analgesic effect of COX-2inhibitor on surgical pain at least partially is mediated by the spinal p-ERK activation and preventive analgesia is more effective for the treatment of postoperative pain clinically.