EXAMINATION OF TONIC NOCICEPTIVE BEHAVIOR USING A METHOD OF SUBSTANCE-P RECEPTOR DESENSITIZATION IN THE DORSAL HORN

Substance P (SP) has been suggested as a neuromediator of nociception in the dorsal horn. Following a single injection of SP onto the rat spinal cord, nociceptive reflexes are facilitated. Following successive administration of a high dose of SP, these responses are attenuated. We have administered multiple injections of SP onto the rat spinal cord in order to produce desensitization to the SP response. With this procedure, we have observed that phasic behaviors (short-term reflex) are attenuated for up to 150 min and are associated with a reduction in the number and affinity of SP-binding sites in the dorsal horn. This study was performed to examine the effect of SP-receptor desensitization in two well-established models of tonic (prolonged) nociception: the formalin test and the monosodium urate (MSU) test. Repeated intrathecal administration of SP (15 mug) reduced the first phase but did not alter the second phase of formalin-induced pain-related behavior. Similarly, repeated administration of SP did not alter MSU-induced pain-related behavior. In both tests, an analgesic dose of morphine administered in combination with SP did reduce the nociceptive behavior. These data show that alteration of SP-receptor activity in the dorsal horn does not alter responses to two longer acting agents considered to be nociceptive. These results suggest that SP in the dorsal horn does not directly mediate tonic nociception but rather may be involved in the expression of phasic pain-related behavior.