Intrathecal edaravone, a free radical scavenger, is effective on inflammatory-induced pain in rats.
BACKGROUND
Free radicals have some roles in inflammation and systemic and local tissue injuries. (Free radical scavengers are neuroprotective against excitotoxic insults.) Therefore, we hypothesized that free radical scavenger would be analgesic on pain induced by excitotoxicity or inflammation. The purpose of this study was to investigate analgesic effects of intrathecally administered edaravone, a free radical scavenger, on thermal and inflammatory pain.


METHODS
Sprague-Dawley rats were implanted with lumbar intrathecal catheters. Edaravone 0.05, 0.1, 0.5, and 1 mg per 20 microl or saline 20 microl (control) were administered intrathecally, and the withdrawal response to thermal stimulation to the tail (tail-flick test) or flinch responses to subcutaneous formalin injection into the hind paw (formalin test) were tested. General behaviour and motor function were also examined. In each dose group, eight rats were used.


RESULTS
No dose-dependent analgesic effects were observed in the tail-flick test. However, dose-dependent analgesia was obtained in both phase 1 and 2 of the formalin test. The 50% effective dose values were 0.25 mg (95% confidence interval, 0.11-0.56 mg) in phase 1 and 0.25 mg (95% confidence interval, 0.061-1.05 mg) in phase 2. No behavioural side-effects nor motor dysfunction was observed, even with the maximum soluble dose (1 mg/20 microl).


CONCLUSIONS
Intrathecally administered edaravone, a free radical scavenger, had analgesic effects on inflammatory-induced acute and facilitated pain but not on acute thermal pain, without any behavioural side-effects.
Nishiyama
T
T
Department of Anaesthesiology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan. nishit-tky@umin.ac.jp
Ogawa
M
M
D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004202:Disinfectants / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D000077553:Edaravone; D005557:Formaldehyde / Q000008:administration & dosage; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000627:therapeutic use*; D006358:Hot Temperature; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology; D007278:Injections, Spinal / Q000379:methods; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors
D004202:Disinfectants; D016166:Free Radical Scavengers; D005557:Formaldehyde; D000077553:Edaravone; D000983:Antipyrine