title: Intracerebroventricular micro-injections of non-steroidal anti-inflammatory drugs abolish reperfusion hyperalgesia in the rat's tail.
abstract: Prostaglandins are mediators of reperfusion hyperalgesia; their site of action may be in the periphery, in the central nervous system, or both. We have investigated whether prostaglandins play a role in the central nervous system during reperfusion hyperalgesia, by intracerebroventricular (i.c.v.) micro-injection of non-steroidal anti-inflammatory drugs (NSAID), to inhibit local prostanoid synthesis. We induced tail ischaemia in conscious rats by applying an inflatable cuff at the base of the tail. The cuff was released at the first signs of co-ordinated escape behaviour. Responses to a noxious thermal stimulus were assessed, by measuring tail flick latency following immersion of the tail in water at 49 degrees C, prior to and immediately after release of the tourniquet. Tail flick latency decreased significantly following ischaemia, that is there was post-ischaemic reperfusion hyperalgesia. Intracerebroventricular micro-injection of NSAID prior to applying the tourniquet had no effect on the co-ordinated escape behaviour during ischaemia or on the tail flick latency after application of a sham tourniquet (uninflated cuff). However all the drugs abolished the hyperalgesia evident during reperfusion. Doses required to abolish hyperalgesia were 0.001 mg/kg indomethacin, 0.08 mg/kg dipyrone, 0.09 mg/kg ibuprofen, 0.2 mg/kg diclofenac sodium and 0.2 mg/kg paracetamol. These doses are 2-3 orders of magnitude less than those necessary to abolish reperfusion hyperalgesia when the same drugs are administered systemically. Our results indicate that the development of reperfusion hyperalgesia of the rat's tail depends on the synthesis of prostanoids within the central nervous system.
authors.affiliation: Brain Function Research Unit, Department of Physiology, University of the Witwatersrand Medical School, Parktown, Johannesburg 2193, South Africa.
authors.forename: Linda
authors.initials: L
authors.lastname: Gelgor
authors.forename: Steven
authors.initials: S
authors.lastname: Cartmell
authors.forename: Duncan
authors.initials: D
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001831:Body Temperature; D004305:Dose-Response Relationship, Drug; D004924:Escape Reaction / Q000502:physiology; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007276:Injections, Intraventricular; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D008845:Microinjections; D010146:Pain; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D015427:Reperfusion Injury / Q000150:complications; D013623:Tail / Q000098:blood supply
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal