PRE TREATMENT WITH MK-801, A NONCOMPETITIVE NMDA ANTAGONIST, PREVENTSDEVELOPMENT 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 intraplan tar 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 mechan ical hyperalgesia measured 27 days later. In contrast, MK-801 administ ration 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 developmen t of mechanical hyperalgesia associated with chronic nerve injury and chronic inflammation differ.