Substance p analogue blocks sp-induced facilitation of a spinal nociceptive reflex

Intrathecal administration of 10 micrograms (6.5 nmoles) of substance P to the lumbar spinal cord of the awake, restrained rat had a biphasic effect on reaction time in the tail-flick test. This effect consisted of an initial decrease at one min after administration, followed five min later by a smaller increase in reaction time. When substance P was given after prior intrathecal administration of 1.55, 3.1 or 6.2 nmoles of [D-Pro2, D-Phe7, D-Trp9]-substance P, the reduction in latency could be blocked in a dose-related manner. The analogue alone failed to alter reaction time but did produce a flaccid paralysis in some cases. Our results support the possibility that substance P is involved in transmission of nociceptive information at the spinal level, but indicate that it does not participate directly in the fast tail withdrawal response. The mechanism of the flaccid paralysis is not understood, but it appears to be a cumulative effect of more than one dose and is likely associated with motor rather than sensory neurones.