Studies on the pharmacological relationship between pain and pruritus.

摘要

There is considerable information in the scientific literature about the pharmacology of pain and the manner in which compounds produce antinociception in animals. Few studies, however, have focused on understanding the antipruritic effects of pharmacological agents due to the fact that there are no established (standard) research models in animals for the investigation of pruritus. Despite many commonalities, the pharmacology of pain has been well characterized, whereas the pharmacology of pruritus remains ill-defined.; We have standardized and validated the compound 48/80 model of histamine-dependent pruritus in an attempt to better understand the pharmacology of the itch/scratch reflex. Using this model, we have demonstrated that selective opioid agonists can antagonize scratching behavior induced by compound 48/80 in mice. Because opioid receptor agonists are known to cause antinociception in standard animal models of pain, we examined the pharmacological bases of pain and itch by comparing the activities of mu-, kappa- and peripherally selective kappa-opioid agonists in an animal model of pain (the acetic acid-induced writhing test or formalin test) and pruritus (the compound 48/80 test). We have found that against each sensation, mu and kappa agonists share similar relative potencies, efficacies, and a common stereoselective mediation of antipruritic and antinociceptive effects.; Because substance P is proposed to play a role as either a neurotransmitter or neuromodulator in the conduction of nociceptive information in the central nervous system, we wished to determine whether substance P was responsible for the pharmacological link we have demonstrated between pain and pruritus. Using intracerebral microdialysis, we determined that substance P release levels in rats were not affected by stimulation with the pruritogenic stimulus as they were with the noxious cold stimulus.; This thesis has demonstrated that compound 48/80-induced scratching, an objective measure of itch, can be attenuated with selective opioid receptor agonists in a similar manner to which they inhibit the sensation of pain, indicating a possible pharmacological commonality between pain and pruritus. In addition, the possible neurotransmitter or neuromodulator of noxious information in the central nervous system, substance P, did not demonstrate any involvement in the transmission of the sensation of pruritus.