Endorphins mediate overshoot of substance P-induced facilitation of a spinal nociceptive reflex

In the awake restrained rat the intrathecal administration of substance P to the lumbar spinal cord abruptly but transiently reduces reaction time in the tail-flick test. Interestingly, this hyperalgesic effect is followed by an increased response time, i.e., a hypoalgesia, which lasts less than 10 min. Administration of naloxone reduces the reaction time. It leaves the initial hyperalgesia unaltered but blocks the hypoalgesia. These results are interpreted as indicating that the initial effect of substance P is independent of any direct or indirect action mediated by opiate receptors. On the other hand, however, the antagonism of the hypoalgesia by naloxone suggests that this response is mediated via opiate receptors and, as substance P and opiates appear not to have any direct interaction at the cellular level, the endorphin-mediated hypoalgesia appears to be reflex in nature. Thus, the rebound overshoot of the response to substance P is visualized as an endorphin-mediated reflex activated by the increased transfer of nociceptive information provoked by substance P. The concept is proposed, therefore, that the transfer of nociceptive information is controlled by a servomechanism, or, in physiological terms, this transfer is under homeostatic control. Indeed, as naloxone itself reduces reaction time, it appears that an endogenous opioid is acting tonically to depress this transfer, at least under the conditions of the present experiments.