substance-p--pro(2)-phe(7)-trp(9)- and Pain

Effects of noxious cutaneous stimulation on the tail flick reflex were examined in the anaesthetized rat. Noxious stimulation was applied by immersing the distal 4 cm of the tail in water at 55 degrees C for 1.5 min. The tail flick reflex was tested at 3 min intervals by applying a noxious radiant heat stimulus to a region of the tail 10 cm proximal to the tip. Tail immersion reduced reaction time to tail flick by 30% and 20% at 0.5 and 3.5 min after immersion, respectively. Reaction time returned to control at 6.5 min and tended to increase above baseline values at 9.5 and 12.5 min. Naloxone (10 mg/kg, i.p.) potentiated the effects of tail immersion on reaction time and prevented the increase above baseline. When the surface temperature of the skin used to evoke the tail flick reflex was raised by 10 degrees C using innocuous radiant heat, reaction time was not significantly different from the control, suggesting that an increase in skin temperature per se is insufficient to account for the response to immersion. Intrathecal administration of a substance P antagonist (1 nmol) attenuated the response to tail immersion. These results indicate that noxious cutaneous stimulation may release an agent in the spinal cord which facilitates the tail flick reflex, and that this agent is antagonized by a substance P antagonist.

Topics: Animals; Hot Temperature; Injections, Spinal; Male; Pain; Rats; Rats, Inbred Strains; Reaction Time; Spinal Cord; Substance P

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.

Topics: Animals; Injections, Spinal; Male; Pain; Rats; Rats, Inbred Strains; Reflex; Spinal Cord; Substance P