Bioquímica e Farmacologia: Acesso Aberto
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Alterations in the Expression of Transcription Factors PPARγ and NFκB in the Brain of Models of Chronic Pain

Amy M Birch#, Jonathan Cheung#, Christianah Oluwadare, James Burton, Wenlong Huang, Amparo Novejarque, Julia Inglis and Magdalena Sastre*

Recent evidence has highlighted the role of nuclear receptors Peroxisome Proliferator-Activated Receptor (PPAR) α and PPARγ in the neuroinflammatory state associated with acute inflammatory and neuropathic pain. Its relevance in the control and treatment of pain has been confirmed by the beneficial effects of treatment with Thiazolidinediones and fibrates. The aim of this study was to evaluate the expression of PPARα, PPARγ, and Nuclear Factor kappa B (NFκB) in the brains of rodent models of inflammatory pain, peripheral neuropathy and peripheral nerve injury, including the collagen induced arthritis (CIA), Spinal Nerve Transection (SNT) and Anti-Retroviral (ART) models. Our results reveal that PPARγ levels are generally reduced in models of persistent pain, while NFκB expression is upregulated, with no major changes in PPARα expression. These alterations seem to be linked with the inflammatory state associated with the CIA model, but are present in nerve damage models as well. This was further confirmed in vitro, using neuroblastoma cells incubated with pro-inflammatory cytokines, with similar changes in the expression of these transcription factors. Therefore, these results point to a common pathway in the aetiologies of these different models contributing to further exacerbation of pain symptomatology and suggest that this pathway may serve as a target for the development of analgesic drugs.