Effects of diclofenac in the rat tail ischaemia--reperfusion injury model of acute hyperalgesia.
The rat tail ischaemia--reperfusion model of acute hyperalgesia described by Gelgor et al. (Pain 24 (1986) 251) has been investigated pharmacologically and electrophysiologically. Despite the advantages of this reusable animal model, biochemical changes associated with the behavioural response have not been determined. After injury+/-subcutaneous diclofenac pretreatment, we investigated the behavioural response (changes to thermally-induced tail flick latency) and measured diclofenac, prostaglandin E(2), 6-keto-prostaglandin F(1 alpha) and thromboxane B(2) concentrations in the tail, spinal cord and brain. Subcutaneous injection of 40 mg kg(-1) diclofenac sodium abolished the hyperalgesic response, suppressed the increased eicosanoid production in the tail, inhibited eicosanoid synthesis in the brain, but gave equivocal effects on eicosanoid concentrations in the spinal cord. Injection of 10 and 20 mg kg(-1) diclofenac reduced the duration of hyperalgesia but did not abolish the behavioural response. Diclofenac concentrations in all three tissues were similar, being approximately 5--10% of the corresponding plasma concentrations. We propose that both central and peripheral mechanisms are associated with the hyperalgesia and that the findings lend indirect support to a central action for non-steroidal anti-inflammatory drugs.
Grace
R F
RF
Department of Anaesthesia and Pain Management, The University of Sydney at Royal North Shore Hospital, St. Leonards, NSW 2065, Australia.
Lin
Y
Y
Edwards
S R
SR
Power
I
I
Mather
L E
LE
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D004008:Diclofenac / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy*; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D015427:Reperfusion Injury / Q000188:drug therapy*; D013623:Tail / Q000098:blood supply*; D013929:Thromboxane B2 / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015777:Eicosanoids; D004008:Diclofenac; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone