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Studies on chronic pain mechanisms in the central nervous system

Chronic pain is one of the most significant medical and scientific challenges in western society today. As well as the emotional and physical effects on the individual it proves to be a significant financial burden to society. Studies have shown that chronic pain leads to central sensitisation that is partially regulated by release of proinflammatory molecules within the CNS. Most work has concentrated on the role of the spinal cord and little is known about changes in supraspinal regions. The CFA footpad model was used to investigate the expression of inflammatory mediators in the brain in persistent inflammatory pain. Using RT-PCR, gene expression of inflammatory mediators was measured in various brain regions. Consistent with previous reports at 7 and 14 days post-injection IL1β expression was significantly elevated in the posterior of the brain (p<0.05), TNFα showed differential expression with a significant increase in the posterior ipsilateral brain region at 72 hours (p<0.05). The chemokine CXCL1 was significantly elevated at 6 hours post-injection (p<0.05) suggesting a role for this chemokine in regulation of the acute pain response. Contrary to evidence from the spinal cord, CX3CL1 and its receptor CX3CR1 were down regulated in the brain at 6 and 24 hours post-injection. Differential expression of astrocyte activation was identified by GFAP immunochemistry. Hypoxia has been implicated in neurodegeneration, a process thought to play a role in chronic pain. Here Hypoxia inducible factor (Hif1α) mRNA expression within the brain was not altered in a CFA model of peripheral inflammation. Interestingly, using Hypoxyprobe immunohistochemistry, a higher level of hypoxia was identified in non-injected controls than in CFA treated animals. This is the first evidence of differential chemokine expression in the brain in persistent inflammatory pain and the first study to suggest a potential role for differential oxygenation within the brain in this condition.
Date January 2011
CreatorsJerina, Helen
ContributorsStevens, Clifford
PublisherUniversity of Bath
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation

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