On the role of NK-2 tachykinin receptors in the mediation of spinal reflex excitability in the rat

The effects of intrathecal administration of neurokinin A, substance P and [Tyr5, D-Trp6,8,9 Arg10]neurokinin A-(4-10) (Men 10207), a specific NK-2 receptor antagonist, on the spinal nociceptive flexor reflex were studied in decerebrate, spinalized, unanesthetized rats. Intrathecal neurokinin A and substance P facilitate the flexor reflex in a similar manner. The reflex facilitation to intrathecal neurokinin A, but not substance P, is dose-dependently blocked by pretreatment with Men 10207. The NK-2 receptor antagonist by itself facilitates the flexor reflex with a potency about 10 times less than that of neurokinin A, indicating a partial agonistic property. Reversible depression of the flexor reflex, which is not due to nonspecific spinal blockade, is observed after 700 pmol Men 10207. Further increasing the dose of Men 10207 to 7 nmol for 20 s at an intensity that activates unmyelinated (C) fibers stimulation of peripheral nerves at 1 Hz for 20 s at an intensity that activates unmyelinated (C) fibers facilitates the ipsilateral flexor reflex. The duration of the facilitation after conditioning stimulation of the cutaneous sural nerve is several minutes and about 1 h after conditioning stimulation of the gastrocnemius muscle nerves. Pretreatment with Men 10207 (70-700 pmol) has no effect on facilitation by the sural nerve conditioning stimulation, but effectively blocks the long-term reflex facilitation to the gastrocnemius nerve stimulation. The present results indicate a distinct role for NK-2 tachykinin receptors in mediation of spinal reflex excitability in the rat. Neurokinin A may be involved in the long-term increase of spinal reflex excitability after activation of unmyelinated fibers innervating muscle.