Use this URL to cite or link to this record in EThOS:
Title: Spinal processing of A-nociceptor inputs in primary and secondary inflammatory hyperalgesia in the rat
Author: Hsieh , Meng-Tzu
ISNI:       0000 0004 5920 6732
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2014
Availability of Full Text:
Access from EThOS:
Hyperalgesia is a symptom of tissue damage and inflammation. In primary hyperalgesia (within the area of injury), there is increased responsiveness to both heat and mechanical stimuli, whereas in secondarY hyperalgesia (outside the area of injury), it is generally reported that responses are only enhanced to mechanical, not heat stimuli. However, recent work from this laboratory has demonstrated that secondary hyperalgesia is A-nociceptor-dependent, rather than being stimulus-modality dependent, explaining the lack of heat but the presence of mechanical hyperalgesia in secondary hyperalgesia. Inflammation leads to changes in the number or affinity of opioid receptors in spinal cord. The segregated expression of delta and mu receptors (DOR & MOR) on A- and C-nociceptors has been recently reported, and is hypothesised to differentially modulate mechanical and thermal nociceptive behaviours respectively. Therefore, the overall aim of work described in this thesis was to investigate how the spinal dorsal horn processes the inputs from different subsets of primary afferent nociceptors in primary and secondary hyperalgesia, and the role of opioid receptors in the regulation of nociceptive processing in the spinal cord. Primary and secondary inflammatOlY hyperalgesia were induced by injection of Freund's Complete Adjuvant into dorsal hindpaw and knee joint respectively. The immediate early gene product Fos was used as a neuronal marker of nociceptive processing in the spinal cord. Using an experimental approach to preferentially activate A- or C-fibre nociceptors, it was found that C-fibre-evoked withdrawal reflexes were facilitated in primary hyperalgesia, whereas A-fibre-evoked withdrawal reflexes were facilitated in secondary hyperalgesia. Additionally, both A- and C-nociceptor stimulations evoked more Fos-like immunoreactivity (FU) in superficial but not deep dorsal horn in the animal model of primary hyperalgesia, whereas FU in response to Abut not C-nociceptor stimulation was increased in the superficial and deep dorsal horn in the animal model of secondary hyperalgesia. Spinal DOR and MOR activation inhibited both C- and A-nociceptor- evoked reflexes in both naives and inflamed animals. The DOR agonist had a greater effect on A-fibre-withdrawal thresholds in secondary hyperalgesia than naives, and a lesser effect on A-fibre-nociception in primary hyperalgesia, suggesting that DOR has a greater contribution to the modulation of A-nociceptor inputs in thermal primary and secondary hyperalgesia than MOR. Spinal DOR activation also had greater anti nociceptive effect on mechanical stimuli than MOR, but these anti nociceptive effects were equivalent in all animals. Spinal MOR activation produced antinociception in mechanical nociception in only secondary hyperalgesia, suggesting the more critical role ofMOR in modulating mechanical pain in secondary hyperalgesia. This study indicates the impOliant role of A-nociceptors in mediating secondary hyperalgesia and the different neuronal mechanisms between primary and secondary hyperalgesia. Such distinctions may be useful in treating clinical syndromes associated with pathophysiological pain.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available