PREEMPTIVE INTRATHECAL ADMINISTRATION OF AN NMDA RECEPTOR ANTAGONIST (AP-5) PREVENTS HYPER-REFLEXIA IN A MODEL OF PERSISTENT VISCERAL PAIN

Dorsal horn sensitization following somatic noxious stimuli is partly mediated by the N-methyl-D-aspartate (NMDA) sub-type of glutamate rece ptor. This phenomenon has been comparatively sparsely investigated in the area of visceral pain. We have therefore investigated the role of spinal NMDA receptors in central sensitization in an animal model of p ersistent visceral pain. In anaesthetized rats the lumbosacral spinal cord was exposed by laminectomy and the pre-emptive effect of intrathe cal AP-5 upon the hyper-reflexia associated with chemical inflammation of the bladder was investigated. The effect of intrathecal AP-5 (an N MDA receptor antagonist) upon the normal cystometrogram (CMG) was also measured. AP-5 (125-1000 mu g) prevented the hyper-flexia associated with bladder inflammation in a dose-dependant fashion. In general, wit hin the dose range 62.5-1000 mu g, AP-5 had no significant effect upon the normal micturition reflex. However, at the top of this dose range a minor non-significant depression of this reflex was noted. NMDA rec eptors do not appear to mediate the micturition reflex at a spinal cor d level. However, they are involved in the induction of hyper-reflexia following urinary bladder inflammation, this hyper-reflexia can be pr evented by pre-emptive intrathecal administration of AP-5.