Two-pore domain potassium channels: emerging targets for novel analgesic drugs: IUPHAR Review 26

Chronic pain is a debilitating and increasingly common medical problem with few effective treatments. In addition to the direct and indirect economic burden of pain syndromes, the concomitant increase in prescriptions for narcotics has contributed to a sharp rise in deaths associated with drug misuse - the 'opioid crisis'. Together, these issues highlight the unmet clinical and social need for a new generation of safe, efficacious analgesics. The detection and transmission of pain stimuli is largely mediated by somatosensory afferent fibres of the dorsal root ganglia. These nociceptive cells express an array of membrane proteins that have received significant attention as attractive targets for new pain medications. Among these, a growing body of evidence supports a role for the two-pore domain potassium (K2P) family of K⁺ channels. Here, we provide a concise review of the K2P channels, their role in pain biology and their potential as targets for novel analgesic agents.