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Title: The primary afferent nociceptor and neuropeptide gene expression : importance in experimental arthritis
Author: Donaldson, Lucy F.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1994
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In these studies, the primary afferent neuronal response to peripheral inflammation with respect to neuropeptide mRNA expression, and the role of the primary afferent and its neuropeptides in the spread of arthritis have been examined. The regulation of neuropeptide genes in DRG during inflammation is not well understood. Blockage of the increase in primary afferent spontaneous activity known to be observed within hours of the onset of inflammation using local anaesthetic prevented the increase in PPT and CGRP mRNA seen in DRG 8 hours after adjuvant injection. While endogenous glucocorticoids have been shown to regulate neuropeptide levels in DRG, adrenalectomy had no effect on the degree or spread of arthritis and had only subtle effects on the expression of PPT and CGRP mRNA. Expression of transcription factors in DRG on noxious stimulation has not been demonstrated, and this has been substantiated in these experiments as expression of NGFI-A, NGFI-B and c-jun was not detectable in DRG innervating inflamed or uninflamed joints. AP-2 mRNA, encoding a transcription factor constitutively expressed in tissue of neural crest origin, showed a rapid increase in expression one hour after injection, returning to control levels within 2 hours. The possible involvement of AP-2 in the regulation of these neuropeptides remains to be determined. In conclusion, these data support the hypothesis that polymodal nociceptors and the neuropeptides they express are closely associated with the maintenance and spread of arthritis. Changes in neuropeptide mRNA expression may be regulated through many mechanisms, including neuronal activity, and transcription factor induction.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available