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