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Intrathecal edaravone, a free radical scavenger, is effective on inflammatory-induced pain in rats


Tomoki Nishiyama, MD, PhD
3-2-6-603, Kawaguchi
Saitama, 332–0015


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 µl or saline 20 µl (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 µl).

Conclusion:  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.