The Role of Pacemaker Currents in Neuropathic Pain

Hyperpolarization-activated cation nonselective cyclic nucleotide-gated (HCN) channels mediate pacemaker currents that control basic rhythmic processes including heartbeat. Alterations in HCN channel expression or function have been described in both epilepsy and cardiac arrhythmias. Recent evidence suggests that pacemaker currents may also play an important role in ectopic neuronal activity that manifests as neuropathic pain. Pacemaker currents are subject to endogenous regulation by cyclic nucleotides, pH and perhaps phosphorylation. In addition, a number of neuromodulators with known roles in pain affect current density and kinetics. The pharmacology of a number of drugs that are commonly used to treat neuropathic pain includes effects on pacemaker currents. Altered pacemaker currents in injured tissues may be an important mechanism underlying neuropathic pain, and drugs that modulate these currents may offer new therapeutic options.