Mao Yan-Fei, Yan Ni, Xu Hua, Sun Ji-Hu, Xiong Yuan-Chang, Deng Xiao-Ming
Department of Anesthesiology, Changhai Hospital, Second Military Medical University, 800 Xiangyin Rd., Shanghai, 200433, PR China.
Brain Res. 2009 Jan 12;1248:68-75. doi: 10.1016/j.brainres.2008.10.073. Epub 2008 Nov 11.
Recent studies indicate that reactive oxygen species (ROS) are involved in persistent pain, including neuropathic and inflammatory pain. Edaravone, a free radical scavenger, which is widely used clinically in Japan for acute cerebral infarction to prevent ischemia reperfusion injury, has been shown to inhibit inflammatory-induced pain in rats. However, it is unknown whether edaravone is effective on neuropathic pain. In the present study, we used the spinal nerve ligation (SNL)-induced neuropathic pain model of rats to investigate the role of edaravone in the generation or development of neuropathic pain. Edaravone was administrated intraperitoneally per day at a dose of 4 mg/kg. We found that preemptive treatment of edaravone had analgesic effects on SNL-induced chronic pain without inducing any behavioral side-effects or motor disturbances at the dose given. By contrast, when administered on the third day after SNL surgery, edaravone cannot reverse the established pain but only produced tenuous analgesic effects on the rats of neuropathic pain. To explore the underlying mechanisms, effects of edaravone on the excitability of dorsal root ganglion (DRG) neurons and activation of JNK in DRG were observed. We found that preemptive edaravone treatment can decrease the H(2)O(2)-induced depolarization in the acutely dissociated DRG neurons. Furthermore, we found that preemptive edaravone treatment can reduce the SNL-induced pJNK expression in the ipsilateral DRG. Taken together, the present study indicated that edaravone could prevent the development of SNL-induced neuropathic pain but had little effects on the established neuropathic pain. The inhibition of the signaling pathway of JNK cascade or suppression of the possible ROS-induced hyper-excitability of DRG neurons might be, at least in part, mechanisms underlying the effects of edaravone on SNL-induced neuropathic pain.
最近的研究表明，活性氧（ROS）参与持续性疼痛，包括神经性疼痛和炎性疼痛。依达拉奉是一种自由基清除剂，在日本临床上广泛用于急性脑梗死以预防缺血再灌注损伤，已被证明可抑制大鼠的炎性疼痛。然而，依达拉奉对神经性疼痛是否有效尚不清楚。在本研究中，我们使用大鼠脊髓神经结扎（SNL）诱导的神经性疼痛模型来研究依达拉奉在神经性疼痛产生或发展中的作用。依达拉奉每天以4mg/kg的剂量腹腔注射。我们发现，依达拉奉的预处理对SNL诱导的慢性疼痛有镇痛作用，在所给剂量下不会引起任何行为副作用或运动障碍。相比之下，在SNL手术后第三天给药时，依达拉奉不能逆转已建立的疼痛，而仅对神经性疼痛大鼠产生微弱的镇痛作用。为了探究潜在机制，观察了依达拉奉对背根神经节（DRG）神经元兴奋性和DRG中JNK激活的影响。我们发现，依达拉奉预处理可降低急性分离的DRG神经元中H₂O₂诱导的去极化。此外，我们发现依达拉奉预处理可降低SNL诱导的同侧DRG中pJNK的表达。综上所述，本研究表明依达拉奉可预防SNL诱导的神经性疼痛的发展，但对已建立的神经性疼痛影响较小。JNK级联信号通路的抑制或对DRG神经元可能由ROS诱导的过度兴奋性的抑制可能至少部分是依达拉奉对SNL诱导的神经性疼痛产生作用的机制。
