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Title: Peripheral changes in NGF in a spared fibre model of neuropathic pain
Author: Evans, Laura Jane
ISNI:       0000 0004 2742 7485
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2012
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The experiments described in this thesis have investigated the role of nerve growth factor (NGF) acting on spared nerve fibres in the pathophysiology of neuropathic pain, caused by a partial nerve injury of the mental nerve, a branch of the trigeminal nerve that innervates the skin and mucosa of the lower lip. The experiments have tested the hypothesis that an over-supply of NGF acts on a reduced population of mental nerve fibres and causes phenotypic changes in the population that could underlie symptoms of neuropathic pain. A behavioural testing protocol was developed to investigate the presence and severity of neuropathic pain to thermal and mechanical stimuli after a chronic constriction injury of the mental nerve. The concentration of NGF in the skin of the lower lip was investigated with an ELISA (enzyme-linked immunosorbant assay) and the neurochemistry of the remaining sensory nerve fibres that innervate the skin of the lip was investigated quantitatively using triple-labelling immunofluorescence. Experiments to determine the time-course of the development of neuropathic pain were conducted initially, and when symptoms were maximal (11, 14 and 21 days post-operatively) further studies on NGF concentration and neurochemical phenotype were performed. A chronic constriction injury of the mental nerve produced cold hyperalgesia in the ipsilateral lower lip 1I days post-injury, although at this time the NGF concentration in the lower lip did not differ between ipsilateral and contralateral sides (ipsilateral = 45±6(SEM) pg/mg, contralateral = 47±7 pg/mg). NGF concentration was significantly increased ipsilaterally compared to contra laterally 14 days post-operatively (ipsilateral = 111±23 pg/mg, contralateral = 69± 13 pg/mg), however, at this time-point there was no behavioural evidence of neuropathic pain. By 21 days post-injury, NGF concentration both ipsilaterally and contralaterally was elevated compared to data for 11 days but there was no significant difference between sides (ipsilateral = 181±31 pg/rng, contralateral = 205±30 pg/rng) and there was also no behavioural evidence of neuropathic pain. Quantitative immunohistochemistry of samples 21 days post-injury showed a significant increase on the ipsilateral side (ipsilateral = 85± 17%, contralateral = 46±5%) in the proportion of nerve fibres that were double-labelled for trkA (the high-affinity NGF receptor) and Calcitonin gene-related peptide (CGRP) and this change was absent at 11 and 14 days post-injury. The data from these investigations suggest that cold hyperalgesia following partial injury to the mental nerve is not induced from an altered concentration of NGF in the skin and that a different mechanism may cause this symptom. Transiently increased NGF on the ipsilateral side may have caused an increased proportion of CGRP immunoreactive fibres in the trkA population and this difference in innervation pattern coincided temporally with mechanical nociceptive thresholds on the ipsilateral side that were lower than those on the contralateral side (due to a lack of habituation which occurred on the contralateral side of chronic constriction injuries and on both sides of sham operated animals).
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available