This study examines a reflex mechanism involved in mediating the inhibition of nociceptive input at a heterosegmental spinal level. This heterosegmental inhibitory mechanism is activated by noxious stimulation of a peripheral body region and is regulated by afferent fibers, local spinal neuronal circuitry and supraspinal structures. / A conditioning stimulus, consisting of immersion of one paw of the lightly anesthetized rat in water at a noxious temperature for 90 s elicited an inhibition of a spinal nociceptive reflex in response to a noxious thermal test stimulus in the tail flick test. The magnitude of this antinociception varied with the intensity of the noxious conditioning stimulus, as immersion in water at 40$ sp circ$C, an innocuous temperature, did not evoke an increase in tail flick latency. The antinociceptive response to noxious conditioning stimuli persisted for 3 to 6 min. The response was observed with noxious thermal stimulation of either the hindpaw or the forepaw. Adult animals treated neonatally with capsaicin, which inhibits development of small diameter unmyelinated afferent fibers, did not show this response, suggesting that unmyelinated afferent fibers mediated the input of the conditioning stimulus. Furthermore, in rats transected at the thoracic level, the antinociception following noxious stimulation of the forepaw was blocked while that following hindpaw stimulation was attenuated, indicating that the conditioning stimulus activated heterosegmental inhibitory mechanisms controlled in part by supraspinal structures and in part by spinal structures. / Systemic preadministration of substance P (NK-1) receptor antagonists blocked the antinociceptive effect. These results support an earlier hypothesis that substance P is involved in the transmission of nociceptive information in the spinal cord. Systemic as well as intrathecal preadministration of opiate receptor antagonists blocked the response in a dose-dependent fashion. Therefore, this study suggests that both substance P and endogenous opioids are involved in mediating heterosegmental inhibitory mechanisms.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.68243 |
| Date | January 1994 |
| Creators | Pitcher, Graham Michael |
| Contributors | Henry, J. L. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001397897, proquestno: AAIMM94501, Theses scanned by UMI/ProQuest. |
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