Opening paths to novel analgesics: the role of potassium channels in chronic pain

Chronic pain is associated with abnormal excitability of the somatosensory system and remains poorly treated in the clinic. Potassium (K(+)) channels are crucial determinants of neuronal activity throughout the nervous system. Opening of these channels facilitates a hyperpolarizing K(+) efflux across the plasma membrane that counteracts inward ion conductance and therefore limits neuronal excitability. Accumulating research has highlighted a prominent involvement of K(+) channels in nociceptive processing, particularly in determining peripheral hyperexcitability. We review salient findings from expression, pharmacological, and genetic studies that have untangled a hitherto undervalued contribution of K(+) channels in maladaptive pain signaling. These emerging data provide a framework to explain enigmatic pain syndromes and to design novel pharmacological treatments for these debilitating states.