Purpose of review: Poor management of chronic pain remains a significant cause of misery with huge socioeconomic costs. Accumulating research in potassium (K+) channel physiology has uncovered several promising leads for the development of novel analgesics.
Recent findings: We now recognize that certain K+ channel subunits are directly gated to pain-relevant stimuli (Kv1.1, K2P) whereas others are specifically modulated by inflammatory processes (Kv7, BKCA, K2P). Genetic analyses illustrate that K+ channel gene variation can predict pain sensitivity (KCNS1, GIRKs), risk for persistent pain (KCNS1, GIRKs, TRESK) and analgesic effectiveness (GIRK2). Importantly, preclinical studies confirm that K+ channel dysfunction can be a pain trigger in traumatic neuropathies (Kv9.1/Kv2.1, Kv7, Kv1.2) and migraine (TRESK). Finally, emerging data suggest that even pain in diabetes, bone cancer and autoimmune neuropathies may have K+ channel dysfunction constituents.
Summary: There is a long-sought need for superior pharmacotherapy of pain syndromes. Although universal enhancement of K+ channel function in the periphery can decrease nociceptive excitability irrespective of the underlying cause, a more refined targeting of subunits with dominant nociceptive roles could yield highly efficacious treatments with fewer side-effects. The ongoing characterization of molecular interactions linking K+ channel dysfunction to pain is instrumental for identifying candidates with the most therapeutic potential.