Zhou X-L, Wang Y, Zhang C-J, Yu L-N, Cao J-L, Yan M
Department of Anesthesiology, School of Medicine, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China.
Jiangsu Province Key Laboratory of Anesthesilogy, Xuzhou Medical College, China.
Eur J Pain. 2015 Oct;19(9):1277-87. doi: 10.1002/ejp.657. Epub 2015 Apr 27.
EphB receptors and their ephrinB ligands are implicated in modulating spinal nociceptive information processing. Here, we investigated whether cyclooxygenase-2 (COX-2), acts as a downstream effector, participates in the modulation of spinal nociceptive information related to ephrinB/EphB signalling.
Thermal hyperalgesia and mechanical allodynia were measured by using radiant heat and von Frey filaments test, respectively. Real-time PCR (RT-PCR) was used to detect the expression of spinal COX-2 mRNA. Spinal COX-2 and extracellular signal-regulated kinase (ERK) protein were determined by Western blot analysis.
Intrathecal injection of ephrinB2-Fc caused thermal hyperalgesia and mechanical allodynia, which were accompanied by increased expression of spinal COX-2 mRNA and protein. Inhibition of spinal COX-2 prevented and reversed pain behaviours induced by the intrathecal injection of ephrinB2-Fc. Blockade of EphB receptors by intrathecal injection of EphB2-Fc reduced complete Freund's adjuvant (CFA)-induced inflammatory pain behaviours, which were accompanied by decreased expression of spinal COX-2 mRNA and protein. Furthermore, treatment with U0126, a mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor, suppressed spinal ERK activation and COX-2 mRNA and protein expression induced by intrathecal injection of ephrinB1-Fc.
These results confirmed the important involvement of COX-2 in the modulation of spinal nociceptive information related to ephrinBs-EphBs signalling.
EphB受体及其ephrinB配体参与调节脊髓伤害性信息处理。在此，我们研究了环氧化酶-2（COX-2）作为下游效应器是否参与与ephrinB/EphB信号相关的脊髓伤害性信息调节。
分别使用辐射热和von Frey细丝试验测量热痛觉过敏和机械性异常性疼痛。采用实时定量聚合酶链反应（RT-PCR）检测脊髓COX-2 mRNA的表达。通过蛋白质免疫印迹分析测定脊髓COX-2和细胞外信号调节激酶（ERK）蛋白。
鞘内注射ephrinB2-Fc可引起热痛觉过敏和机械性异常性疼痛，同时伴有脊髓COX-2 mRNA和蛋白表达增加。抑制脊髓COX-2可预防和逆转鞘内注射ephrinB2-Fc诱导的疼痛行为。鞘内注射EphB2-Fc阻断EphB受体可减轻完全弗氏佐剂（CFA）诱导的炎性疼痛行为，同时伴有脊髓COX-2 mRNA和蛋白表达降低。此外，用丝裂原活化蛋白/细胞外信号调节激酶激酶（MEK）抑制剂U0126处理可抑制鞘内注射ephrinB1-Fc诱导的脊髓ERK激活以及COX-2 mRNA和蛋白表达。
这些结果证实COX-2在与ephrinB-EphB信号相关的脊髓伤害性信息调节中起重要作用。
