Targeting nicotinic acetylcholine receptors for the treatment of pain

Abstract

Nicotine and nicotinic acetylcholine receptors (nAChRs) have been explored for the past three decades as a strategy for pain management. These receptors are widely expressed throughout the central and peripheral nervous systems and in immune cells. Despite encouraging results with many selective a4Β2? nAChR agonists in animal models of pain, human studies showed a narrow therapeutic window between analgesic efficacy and toxicity. However, several recent developments have generated new opportunities for the use of nicotinic agents as analgesics. Accumulating evidence suggests that a7 nAChR agonists and a9a10 nAChR antagonists are promising agents for the treatment of chronic pain, including inflammatory and neuropathic conditions. Recent animal studies also promote the therapeutic potential of other nAChR ligands, such as positive allosteric modulators and silent agonists. This chapter highlights these recent developments and outlines important findings that demonstrate the potential for further development of nAChR ligands as novel analgesics.