This study investigates the role of substance P and NK-1 receptors in an animal model of neuropathic pain. Unlike naive animals, innocuous peripheral stimulation of neuropathic animals was determined to cause heterosegmental inhibition in the tail-flick test as well as increased plasma extravasation in the paw. These effects were prevented by administration of CP-96,345 before stimulation. Additionally, CP-96,345 or an antisense oligonucleotide against NK-1 receptors significantly alleviated mechanical allodynia in neuropathic animals. Finally, mass spectrum of lumbar spinal cord of neuropathic but not naIve animals showed a significant upregulation of substance P. We conclude that innocuous stimulation of a neuropathic area could trigger activation of NK-1 receptors, presumably due to binding of substance P. Furthermore, this activation of NK-1 receptors could be central to the perception of mechanical allodynia in neuropathic pain. These results justify the investigation of inhibiting the interaction between substance P and the NK-1 receptor for the treatment of drug resistant neuropathies.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.78358 |
| Date | January 2002 |
| Creators | Fallis, Brooks A. |
| Contributors | Henry, James 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: 001974366, proquestno: AAIMQ88193, Theses scanned by UMI/ProQuest. |
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