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 nocicep tive responses evoked by acute stimulation of normal somatic tissues, but r ather are involved in hyperalgesic responses after peripheral injury and in flammation. Previous studies from this laboratory have shown important diff erences in the neural organization of somatic and visceral nociceptive path ways. Here, we have explored the role of NMDA receptors in processing acute visceral noxious input, compared with somatic noxious input. The left uret er was cannulated close to the bladder in adult female Wistar rats anaesthe tized 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 ketam ine 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). Gra ded pinch stimuli (30 s, 2-4 N) of one hind-paw evoked similar presser resp onses 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 do se range used neither ketamine nor Mrz 2/576 inhibited a presser response o f non-nociceptive origin (produced by bilateral carotid occlusion) whereas memantine did. Thus the effects of memantine are likely due to a non-specif ic cardiovascular effect. These results show that NMDA receptor antagonists inhibit nociceptive reflexes evoked from the normal ureter, and suggest th at NMDA receptors are involved in the processing of acute nociceptive input s from viscera. We conclude that acute stimulation of normal visceral tissu e provokes intense responses that recruit neural mechanisms mediated by NMD A receptors. However, in somatic pathways, these mechanisms are recruited o nly by an enhanced peripheral input such as that produced after injury or i nflammation. (C) 1999 International Association for the Study of Pain. Publ ished by Elsevier Science B.V.