Effects of N-methyl-D-aspartate antagonists and spantide on spinal reflexes and responses to substance P and capsaicin in isolated spinal cord preparations from mouse and rat.

Electrical stimulus intensity, capsaicin, excitatory amino acid antagonists and the substance P antagonist, spantide, have been used to investigate the roles of primary afferent C fibres and excitatory amino acid receptors in the generation of long duration (half time 9.1 s +/- 1.1 S.E.M., N = 24) contralateral reflexes recorded in ventral roots of immature rat spinal cords in vitro. The relationship between C fibre compound action potentials recorded in the dorsal root and duration of the dorsal root-evoked contralateral ventral root potential appeared to be coincidental rather than causal. Dorsal root-evoked contralateral ventral root potentials of greater than 2 s in duration could not be evoked in mature mouse spinal preparations. Application of capsaicin (1 microM for 15-120 min) produced a long lasting increase in spontaneous activity of ventral roots as well as blockade of C fibre conduction in dorsal roots. The dorsal root potential evoked following stimulation of adjacent dorsal roots at intensities insufficient for activation of C fibres was depressed by capsaicin. Dorsal root-evoked contralateral ventral root potentials were abolished by kynurenate (EC50 56 +/- 13 microM, N = 3) and depressed to 38.2 +/- 6.9% S.E.M. (N = 7) of pre-drug levels by the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonopentanoate (20 microM) or to 51.8 +/- 9.0% (N = 7) by the substance P analogue spantide (33 microM). Spantide consistently antagonised substance P-induced, but not capsaicin-induced, depolarizations recorded in ventral roots (+-)-2-Amino-5-phosphonopentanoic acid (10-50 microM) depressed both substance P- and capsaicin-induced depolarizations. The depressant effect of spantide, unlike that of (+/-)-2-amino-5-phosphonopentanoic acid, was associated with a long lasting excitatory action. In the presence of tetrodotoxin (0.1 microM), spantide (33 microM) failed to antagonize substance P-induced depolarizations. It is suggested that long duration of the dorsal root-evoked contralateral ventral root potential is a consequence of the activation of the N-methyl-D-aspartate receptor operated ion channels by excitatory amino acid transmitters.