What Is the Role of 2-Pore Domain Potassium Channels (K2P) in Pain?

Nociceptive dorsal root ganglion (DRG) and trigeminal neurons express a large numbers of ion channels that determine their threshold and responses to both noxious and innocuous stimuli.(1) Several voltage-gated sodium channels (Na-v),(2) voltage-gated calcium (Ca2+) channels,(3) transient receptor potential (TRP) channels,(4) and other cation channels increase nociceptor responsiveness, whereas a variety of potassium (K+) channels prevent spontaneous nociceptor activity and reduce their firing probability.(5-9) The imbalance between these 2 opposing influences, which may occur as a consequence of channel gene sequence variants,(10) effect of inflammatory mediators,(11) or transcriptional dysregulation,(12,13) promotes neuropathic pain, hyperalgesia, and allodynia.(14) Given their importance in pain modulation, voltage-gated K+ channels (K-v) and 2-pore domain K+ channels (K2P) are potential targets for designing novel analgesic compounds.(6,14-17) This review will focus on K2P channels, which are multimodal sensors that may have an important role in several pain disorders, including neuropathic pain and migraine(6,15-20)