Differential effects of N-Methyl-D-aspartate receptor blockade on nociceptive somatic and visceral reflexes

N-methyl-D-aspartate (NMDA) receptors appear to play little part in nociceptive responses evoked by acute stimulation of normal somatic tissues, but rather are involved in hyperalgesic responses after peripheral injury and inflammation. Previous studies from this laboratory have shown important differences in the neural organization of somatic and visceral nociceptive pathways. Here, we have explored the role of NMDA receptors in processing acute visceral noxious input, compared with somatic noxious input. The left ureter was cannulated close to the bladder in adult female Wistar rats anaesthetized with pentobarbitone (50 mg/kg i.p). Graded distentions of the ureter (30 s, 25-80 mmHg) evoked increases in blood pressure. These responses were dose-dependently inhibited by the NMDA receptor ion channel blockers ketamine and memantine (ID50 = 2.4 +/- 1.6 and 14.5 +/- 1.3 mg/kg, i.v.), and by the Merz glycine site antagonist Mrz 2/576 (ID50 = 0.2 +/- 0.2 mg/kg). Graded pinch stimuli (30 s, 2-4 N) of one hind-paw evoked similar presser responses which were not affected by ketamine (up to 10 mg/kg). Similarly, Mrz 2/576 did not affect responses to noxious pinch, whereas memantine (ID50 = 17 +/- 12 mg/kg) did inhibit responses to pinch stimuli. However, in the dose range used neither ketamine nor Mrz 2/576 inhibited a presser response of non-nociceptive origin (produced by bilateral carotid occlusion) whereas memantine did. Thus the effects of memantine are likely due to a non-specific cardiovascular effect. These results show that NMDA receptor antagonists inhibit nociceptive reflexes evoked from the normal ureter, and suggest that NMDA receptors are involved in the processing of acute nociceptive inputs from viscera. We conclude that acute stimulation of normal visceral tissue provokes intense responses that recruit neural mechanisms mediated by NMDA receptors. However, in somatic pathways, these mechanisms are recruited only by an enhanced peripheral input such as that produced after injury or inflammation. (C) 1999 International Association for the Study of Pain. Published by Elsevier Science B.V.