Potassium channels and pain:: present realities and future opportunities

Four families of potassium channels with different structures, functional characteristics and pharmacological sensitivity, are distinguished in neurons: voltage-gated (K-v), calcium-activated (K-ca), inward rectifier (K-ir) and two-pore (K-2P) K+ channels. During the last 15 years, numerous studies have demonstrated that the opening of some of these K+ channels plays an important role in the antinociception induced by agonists of many G-protein-coupled receptors (alpha(2)-adrenoceptors, opioid, GABA(B), muscarinic M-2, adenosine A(1), serotonin 5-HT1A and cannabinoid receptors), as well as by other antinociceptive drugs (nonsteroidal antiinflammatory drugs [NSAIDs], tricyclic antidepressants, etc.) and natural products. Several specific types of K+ channels are involved in antinociception. The most widely studied are the ATP-sensitive K+ channels (K-ATP), members of the K-ir family, which participate in the antinociception induced by many drugs that activate them in both the central and the peripheral nervous system. The opening of G-protein-regulated inwardly rectifying K+ channels (GIRK or K(ir)3), K(v)1.1 and two types of K-Ca channels, the small- and large-conductance calcium-activated K+ channels (SK and BK channels, respectively), also play a role in the antinociceptive effect of different drugs and natural products. Recently, drugs that open K+ channels by direct activation (such as openers of neuronal K(v)7 and K-ATP channels) have been shown to produce antinociception in models of acute and chronic pain, which suggests that other neuronal K+ channels (e.g. K(v)1.4 channels) may represent an interesting target for the development of new K+ channel openers with antinociceptive effects. (C) 2004 Elsevier B.V. All rights reserved.