PROFILE OF NEURONAL EXCITATION FOLLOWING SELECTIVE ACTIVATION OF THE NEUROKININ-1 RECEPTOR IN RAT DEEP DORSAL HORN IN-VITRO

The excitatory actions of the selective neurokinin-1 receptor (NK1R) a gonist [Sar(9),Met(O-2)(11)]substance P (SP) were tested on a sample ( n = 50) of deep dorsal horn neurones in the isolated and hemisected yo ung rat spinal cord. Superfusion of the NK1R agonist (2 mu M) elicited a prolonged membrane depolarisation (6.6 +/- 0.5 mV) and an increase in action potential firing in 41/50 (82%) neurones. These [Sar(9),Met( O-2)(11)]SP-induced depolarisations were attenuated by the selective N K1R antagonist GR82334 (1 mu M). An increased neuronal excitability af ter [Sar(9),Met(O-2)(11)]SP application was indicated by an augmented spike frequency generated in response to long duration, step depolaris ations. In order to assess whether a direct excitatory action existed, [Sar(9),Met(O-2)(11)]SP was re-tested on a sample of TTX-treated neur ones (n = 14). The majority (9/14) retained agonist sensitivity althou gh the amplitude of the depolarisation was reduced to 48% of the contr ol value. A sample of neurones (n = 7) that responded to the NK1R agon ist were morphologically characterised after filling with the intracel lular dye, biocytin. Dorsal dendrites that clearly penetrated lamina I I and that could receive a direct C-afferent input, were identified in only 2/7 neurones. These electrophysiological and neuroanatomical dat a demonstrate that deep dorsal horn neurones possess functional NK1Rs. The implications of the existence of these NK1Rs in the context of sp inal somatosensory systems and SP is considered. (C) 1997 Elsevier Sci ence B.V.