Pre treatment with MK-801, a non-competitive NMDA antagonist, prevents development of mechanical hyperalgesia in a rat model of chronic neuropathy, but not in a model of chronic inflammation.
In the rat, loose ligation of the sciatic nerve results in behavioural signs of hyperalgesia reminiscent of neuropathy in man. A further rat model, of chronic inflammatory hyperalgesia, is produced by intraplantar administration of Freund's complete adjuvant (FCA). We report here that preemptive administration of a non-competitive antagonist of the glutamate N-methyl-D-aspartate (NMDA) receptor, MK-801 (0.3 mg kg-1, s.c.) 30 min prior to and twice daily for a further 8 days following loose ligation of the sciatic nerve, blocks the development of mechanical hyperalgesia measured 27 days later. In contrast, MK-801 administration using the same dosing regimen did not significantly inhibit the hyperalgesia apparent 15 days following i.pl. administration of FCA. Our results suggest that the mechanisms responsible for the development of mechanical hyperalgesia associated with chronic nerve injury and chronic inflammation differ.
Department of Gastrointestinal Pharmacology, Glaxo Group Research Ltd., Ware, Herts., UK.
G D
GD
Smith
J
J
Wiseman
S M
SM
Harrison
P J
PJ
Elliott
P J
PJ
Birch
D000818:Animals; D002908:Chronic Disease; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000209:etiology / Q000517:prevention & control*; D007249:Inflammation / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D009422:Nervous System Diseases / Q000150:complications* / Q000503:physiopathology; D009619:Nociceptors / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012584:Sciatic Nerve / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D005620:Freund's Adjuvant