EVIDENCE FOR A ROLE OF TACHYKININ NK(2)-RECEPTORS IN MEDIATING BRIEF NOCICEPTIVE INPUTS TO RAT DORSAL HORN (LAMINAE III-V) NEURONS

Since the NK2 receptor-selective tachykinin, neurokinin A is present in fine primary afferent neurons in addition to the NK1 receptor-selective tachykinin, substance P, we have addressed the relative role of NK1 and NK2 receptors in somatosensory processing in spinal dorsal horn. Recording extracellularly from rat laminae III-V neurons whilst ionophoresing drugs nearby, the selective NK1 receptor antagonists L 688,169, GR 82334 and [D-Pro4,D-Trp7,910Phe11]substance P-(4-11) failed to influence neuronal responses to cutaneous pinch or noxious heat but often enhanced responses to innocuous brush. In contrast, the highly selective NK2 receptor antagonist L 659,874 profoundly inhibited responses to noxious heat but not pinch or brush. Highly selective synthetic agonists for both NK1 and NK2 receptors ([N-acetyl-Arg6,Sar9,Met(O2)11]substance P-(6-11) and GR 64349, respectively) and also NKA showed the inverse effects on sensory responses to those brought about by their antagonists. At higher ionophoretic currents, both NK1 and NK2 receptor agonists increased spontaneous activity. This increased basal firing induced by GR 64349 and neurokinin A (but not that due to [N-acetyl-Arg6,Sar9,Met(O2)11]substance P-(6-11) appeared to partially pre-empt further excitatory responses to noxious heat. It is concluded that although both NK1 and NK2 receptors can clearly mediate excitation of dorsal horn neurons, it is not NK1, but rather NK2 receptors that are important as the physiological transducer of brief thermal nociceptive inputs in this model.