Low doses of N-methyl-D-aspartate antagonists in superficial laminae of medulla oblongata facilitate wind-up of convergent neurones

In this study. a trigeminal model was used in which high threshold C-fibre- evoked activities of convergent neurotics located in the subnucleus oralis of the trigeminal complex are modulated through the superficial part. the s ubstantia gelatinosa, of the subnucleus caudalis. The two subnuclei are loc ated 3 min apart, therefore, it was possible to inject dizocilpine, a non-c ompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. into either the superficial or the deep parts of subnucleus caudalis without interfering w ith ongoing recording of convergent neurotics in subnucleus oralis. A diffe rential NMDA-dependent modulation of wind-up was observed according to the dose and the injection target. (1) The injections of small non-diffusible d oses (0.12 mug) of dizocilpine into the superficial part of subnucleus caud alis facilitated wind-up. The effect peaked at 25 min with a mean increase above control of 173 +/- 31%. Injection (0.5 mug) of either the less active enantiomer dizocilpine or saline into superficial subnucleus caudalis had no significant effect on subnucleus oralis convergent neurotics, This sugge sts that NMDA-dependent interneurones, probably located in substantia gelat inosa of subnucleus caudalis, exert, in normal conditions, an inhibitory co ntrol on wind-up of convergent subnucleus oralis neurotics. (2) The injecti on of larger doses (0.5 mug) into the superficial part of subnucleus caudal is induced a predominant inhibitory effect on wind-up. The mean peak effect at 15 min was 46 +/- 7% compared to control (100%). Small and large doses of dizocilpine injected into the deep part of subnucleus caudalis had a pre dominant inhibitory effect. The inhibition of wind-up of subnucleus oralis neurones after injection of NMDA receptor antagonists in superficial or deep subnucleus caudalis indica tes that wind-up may be due, at least in part, to NMDA activation at synaps es that do not involve the recorded convergent neurotics. (C) 2001 IBRO. Pu blished by Elsevier Science Ltd. All rights reserved.