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Title: Temporal expression of neurochemical markers in primary sensory neurones in traumatic and non-traumatic models of neuropathic pain
Author: Boateng, Edward
ISNI:       0000 0004 2737 7174
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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Introduction: Expression of neurochemical markers in dorsal root ganglion (DRG) has been shown to underlie nerve injury induced neuropathic pain and are usually examined once post injury in rodent models. Here I hypothesize that neurochemical markers are expressed differentially at various time points post nerve injury and that expression of these markers differ between traumatic and non-traumatic models of neuropathic pain, thus reflecting variations in pathophysiology. In two different rat models of neuropathic pain, namely, the tibial nerve transection (TNT) and the d4T (HIV antiretroviral drug) associated toxic neuropathy; immunohistochemical labelling was used to determine the expression of various neurochemical markers across time. Double labelling with peripherin or NF-200 (labels small and large neurons respectively) and a cell size analysis were conducted to validate cellular phenotype. Pain behaviour was measured in vivo using mechanical and thermal hypersensitivity assays. To confirm tibial nerve distribution in the DRGs, Fluorogold retrograde labelling was performed. I also explored the effect of the omega-3 polyunsaturated fatty acid dicosahexonoic acid (DHA) on TNT associated mechanical hypersensitivity and inflammation, as previous studies have shown DHA to be both anti-inflammatory and neuroprotective in animal models of spinal cord injury and stroke, and therefore could be relevant in peripheral nerve injury. Results: [Table of results appears here. To view, please open pdf attachment] From day 7, TNT rats developed mechanical hypersensitivity (↓62% from baseline at peak, day 28). Rats injected with d4T exhibited bilateral hind paw mechanical hypersensitivity (↓~47% from baseline at peak, day 22), but failed to exhibit any neurochemical changes in the DRG such as that observed in TNT injury. Seven days following Fluorogold injection into the tibial nerve of naive rats, labelling was identified in the L4 (38.5%) and L5 (27.5%) DRGs. Since DHA did not alter TNT induced mechanical hypersensitivity, key neurochemical markers were not evaluated. Investigations examined the potential of DHA to modulate the DRG macrophage response, and revealed no differences compared to saline controls at day 28 post TNT injury. Conclusion: The results of the study demonstrate completely different expression patterns of neurochemical markers following TNT injury and treatment with d4T, and highlight the mechanistic difference between nerve trauma and antiretroviral associated neuropathic pain.
Supervisor: Rice, Andrew Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral