Alterations in the Expression of Transcription Factors PPARγ and NFκB in the Brain of Models of Chronic Pain

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

doi:10.4172/2167-0501.1000217

Abstract

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.

Highlights

Despite chronic pain being a widespread health issue, current management and treatments for the condition are far from satisfactory [1]
The expression of Peroxisome Proliferator-Activated Receptor (PPAR) and NFκB is altered in animal models of chronic pain To allow better understanding towards the underlying mechanisms involved in the generation of chronic pain in the CNS, we investigated the potential changes in the expression of transcription factors NFkB and PPARs in the brain of collagen induced arthritis (CIA), Spinal Nerve Transection (SNT), and ART models of chronic pain
No major changes were detected in PPARα expression in brains of the SNT and CIA models, PPARα levels were reduced in certain brain areas of the ART model of pain (Figure 3)

Summary

Introduction

Despite chronic pain being a widespread health issue, current management and treatments for the condition are far from satisfactory [1]. Inflammation can be a consequence of conditions such as neuropathic pain, where inflammation is secondary to damage to the somatosensory nervous system [4] Inflammatory mediators, such as prostaglandins, nerve growth factor, nitric oxide, cytokines, and chemokines are released from injury sites and can activate or modify nociceptor activities. This directly elicits various forms of pain, resulting in peripheral and central sensitisation and a chronic pain state [5,6,7]. NSAIDs inhibit the synthesis of prostaglandins, diminishing peripheral and central sensitization It is not fully understood whether the inflammatory mediators cause and or maintain neuropathic pain

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