Mechanisms of paresthesias arising from healthy axons

Paresthesias are common manifestations of central and peripheral pathologic al processes and are due to ectopic impulse activity in cutaneous afferents or their central projections. Cutaneous afferents are more excitable than motor axons, due to differences in their biophysical properties. These diff erences probably include more persistent Na+ conductance and inward rectifi cation on cutaneous afferents, properties which probably confer greater pro tection from impulse-dependent conduction failure but create a greater tend ency to ectopic activity. Ectopic discharges can be induced in normal affer ents by four maneuvers: hyperventilation, ischemia, release of ischemia, an d prolonged tetanization. The alkaline shift produced by hyperventilation s electively increases the persistent Na+ conductance, while the membrane dep olarization produced by ischemia affects both transient and persistent Nachannels. Postischemic and posttetanic paresthesias occur when hyperpolariz ation by the Na+/K+ pump is transiently prevented by raised extracellular K +. The electrochemical gradient for K+ is reversed, and inward K+ currents trigger regenerative depolarization. These mechanisms of paresthesia genera tion can account for paresthesias in normal subjects and may be relevant in some peripheral nerve disorders. (C) 2000 John Wiley & Sons. Inc. Muscle N erve 23: 310-320, 2000.