The general aim of the experiments conducted for this thesis was to determine whether there are morphological changes in the innervation of the skin underlying states of neuropathic pain. More specifically, this thesis was immediately addressing the question of whether autonomic fibers sprout de novo into the upper dermis of the rat lower lip following bilateral chronic constriction injury (CCI) of the mental nerve, a purely sensory branch of the trigeminal. In addition to the main objective, we sought to determine whether and to what extent the peptidergic and non-peptidergic populations of primary afferent sensory fibres were affected following CCI. Due to the results we obtained, we also tested for any up regulation of the high-affinity NGF receptor trkA on primary afferent fibres following CCI as a possible trigger for the sprouting of both sympathetic and peptidergic fibres. Most importantly, we wanted to determine if there was a behavioural correlate to the different patterns of innervation observed by both autonomic and primary afferent fibers following CCI. / Our findings indicate that 4 weeks following CCI injury of the mental nerve there is an abundant sprouting of both sympathetic and parasympathetic fibres into the upper dermis, a region of skin from which they are normally absent. In addition, we have demonstrated that peptidergic population of nociceptive fibres display a robust sprouting into the upper dermis which is maximal at the same time point as autonomic fibre migration. Interestingly however, we also demonstrate that in the epidermis, both populations of sensory fibers experience a significant decrease in density at 2 weeks post-CCI, followed by fibre re-growth at levels above those seen in sham-operated animals at 4 weeks post-CCI; however, this increase was only statistically significant for the nonpeptidergic population. Furthermore, the high-affinity NGF receptor, trkA, is up-regulated on CGRP-IR fibres with a peak at 4 weeks post CCI. Finally, we observed behavioural evidence for spontaneous pain or dysesthesiae at the time point when there is sprouting of both autonomic and sensory fibres.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.84036 |
| Date | January 2005 |
| Creators | Grelik, Cynthia |
| 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 Pharmacology and Therapeutics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002262140, proquestno: AAIMR22728, Theses scanned by UMI/ProQuest. |
Page generated in 0.0024 seconds