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.