title: Emerging potassium channel targets for the treatment of pain.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
authors: Christoforos
authors: C
authors: Tsantoulas
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D059350:Chronic Pain / Q000188:drug therapy* / Q000209:etiology; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000503:physiopathology; D015195:Drug Design; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D008881:Migraine Disorders / Q000188:drug therapy / Q000503:physiopathology; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D010149:Postoperative Pain / Q000188:drug therapy / Q000503:physiopathology; D015221:Potassium Channels / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000700:Analgesics; D015221:Potassium Channels