Targeting Nuclear Receptors for Chronic Inflammatory Pain: A Potential Alternative

Pain is the unpleasant consequence of detrimental neuronal activity that can be triggered by chronic inflammation, noxious stimuli, and nerve damage. In the case of chronic inflammatory pain, the establishment and maintenance of pain states often depend on the chronic activation and immune response occurring at the site of the peripheral nerve injury. Many current analgesic drugs lack efficacy in long-term pain management. Targeting the nuclear receptor family of transcription factors may provide a novel avenue for the treatment of chronic inflammatory pain. Peroxisome proliferator-activated receptor (PPAR) ligands have demonstrated efficacy in several diabetic-related neuropathic pain models, while the REV-ERB receptors play a key role in the regulation of both P2X7 receptor expression and NLRP3 inflammasome expression and activation. As such, activating the REV-ERB receptor may provide an anti-inflammatory and analgesic option for chronic inflammatory pain sufferers.