Edaravone, a free radical scavenger, is effective on neuropathic pain in rats.
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.
Mao
Yan-Fei
YF
Department of Anesthesiology, Changhai Hospital, Second Military Medical University, 800 Xiangyin Rd., Shanghai, 200433, PR China.
Yan
Ni
N
Xu
Hua
H
Sun
Ji-Hu
JH
Xiong
Yuan-Chang
YC
Deng
Xiao-Ming
XM
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D002908:Chronic Disease; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000503:physiopathology; D053612:Janus Kinases / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy* / Q000517:prevention & control; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000293:injuries
D000700:Analgesics; D016166:Free Radical Scavengers; D053612:Janus Kinases; D000077553:Edaravone; D000983:Antipyrine