Guo Ya-Jing, Shi Xu-Dan, Fu DI, Yang Yong, Wang Ya-Ping, Dai Ru-Ping
Institute of Combined Traditional Chinese and Western Medicine, Xiangya Hospital of Central South University, Changsha, Hunan 410011;
Exp Ther Med. 2013 Jul;6(1):275-279. doi: 10.3892/etm.2013.1118. Epub 2013 May 15.
Cyclooxygenase (COX)-2 inhibitors are widely used for postoperative pain control in clinical practice. However, it is unknown whether spinal sensitization is involved in the analgesic effects of COX-2 inhibitors on surgical pain. Extracellular signal-regulated kinase (ERK) in the spinal cord is implicated in various types of pain, including surgical pain. The present study investigated the role of spinal ERK signaling in the analgesic effect of the COX-2 inhibitor parecoxib on surgical pain. Surgical pain was produced in rats by surgical incision of the hind paw. Phosphorylated (p)-ERK1/2 expression was determined by immunohistochemistry. Pain hypersensitivity was evaluated by measuring the paw withdrawal threshold using the von Frey test. The selective COX-2 inhibitor parecoxib was delivered 20 min before or 20 min after the incision by intraperitoneal injection. Pretreatment with parecoxib markedly attenuated the pain hypersensitivity induced by incision. However, post-treatment with parecoxib produced minimal analgesic effects. Parecoxib inhibited the increase in spinal p-ERK expression following surgical incision. The present study thus suggests that the COX-2 inhibitor parecoxib exerts its analgesic effect on surgical pain through the inhibition of neuronal ERK activation in the spinal cord. COX-2 inhibitor delivery prior to surgery has more potent analgesic effects, suggesting the advantage of preventive analgesia for post-operative pain control.
环氧化酶（COX）-2抑制剂在临床实践中被广泛用于术后疼痛控制。然而，尚不清楚脊髓敏化是否参与COX-2抑制剂对手术疼痛的镇痛作用。脊髓中的细胞外信号调节激酶（ERK）与包括手术疼痛在内的各种类型疼痛有关。本研究调查了脊髓ERK信号在COX-2抑制剂帕瑞昔布对手术疼痛的镇痛作用中的作用。通过后爪手术切口在大鼠中产生手术疼痛。通过免疫组织化学测定磷酸化（p）-ERK1/2表达。使用von Frey试验通过测量爪退缩阈值来评估疼痛超敏反应。选择性COX-2抑制剂帕瑞昔布在切口前20分钟或切口后20分钟通过腹腔注射给药。帕瑞昔布预处理显著减轻了切口诱导的疼痛超敏反应。然而，帕瑞昔布治疗后产生的镇痛作用最小。帕瑞昔布抑制了手术切口后脊髓p-ERK表达的增加。因此，本研究表明COX-2抑制剂帕瑞昔布通过抑制脊髓中神经元ERK激活对手术疼痛发挥镇痛作用。术前给予COX-2抑制剂具有更强的镇痛作用，表明预防性镇痛在术后疼痛控制中的优势。
