Attenuation of reperfusion hyperalgesia in the rat by systemic administration of benzodiazepines.
1. An investigation into whether reperfusion hyperalgesia is modulated by prior systemic administration of two benzodiazepine agonists (diazepam and chlordiazepoxide), and an antagonist (flumazenil) was conducted. 2. Transient ischaemia was induced in conscious rats by applying an inflatable tourniquet to the base of the tail; when the rats exhibited a co-ordinated escape response, the tourniquet was deflated and reperfusion of the tail was allowed. Reperfusion hyperalgesia manifested as a decrease in tail flick latency, following tail immersion in 49 degrees C water, after the release of the tourniquet. 3. Intraperitoneal administration of diazepam, chlordiazepoxide and flumazenil had no effect on the co-ordinated escape to the noxious ischaemic stimulus nor on tail flick latency after application of a sham tourniquet. 4. The hyperalgesia evident during reperfusion, was abolished by diazepam (1 and 5 mg kg-1) and chlordiazepoxide (5 and 25 mg kg-1). The antihyperalgesic effects of both diazepam (5 mg kg-1) and chlordiazepoxide (25 mg kg-1) were inhibited by flumazenil (1 mg kg-1). 5. Rotarod performance was impaired in rats given diazepam and chlordiazepoxide at the same doses at which the benzodiazepines were antihyperalgesic. The impairment to motor function did not extend to the motor systems involved in the tail flick response. 6. In conclusion, benzodiazepines have antinociceptive properties during hyperalgesia.
Cartmell
S M
SM
Department of Physiology, University of the Witwatersrand Medical School, Johannesburg, South Africa.
Mitchell
D
D
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000494:pharmacology*; D002707:Chlordiazepoxide / Q000494:pharmacology; D003864:Depression, Chemical; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D015427:Reperfusion Injury / Q000188:drug therapy*; D013623:Tail / Q000098:blood supply
D011957:Receptors, Opioid; D001569:Benzodiazepines; D009270:Naloxone; D005442:Flumazenil; D002707:Chlordiazepoxide; D003975:Diazepam