Painful neuropathy decreases membrane calcium current in mammalian primary afferent neurons.
Hyperexcitability of the primary afferent neuron leads to neuropathic pain following injury to peripheral axons. Changes in calcium channel function of sensory neurons following injury have not been directly examined at the channel level, even though calcium is a primary second messenger-regulating neuronal function. We compared calcium currents (I(Ca)) in 101 acutely isolated dorsal root ganglion neurons from 31 rats with neuropathic pain following chronic constriction injury (CCI) of the sciatic nerve, to cells from 25 rats with normal sensory function following sham surgery. Cells projecting to the sciatic nerve were identified with a fluorescent label applied at the CCI site. Membrane function was determined using patch-clamp techniques in current clamp mode, and in voltage-clamp mode using solutions and conditions designed to isolate I(Ca). Somata of peripheral sensory neurons from hyperalgesic rats demonstrated decreased I(Ca). Peak calcium channel current density was diminished by injury from 3.06+/-0.30 pS/pF to 2. 22+/-0.26 pS/pF in medium neurons, and from 3.93+/-0.38 pS/pF to 2. 99+/-0.40 pS/pF in large neurons. Under these voltage and pharmacologic conditions, medium-sized neuropathic cells lacked obvious T-type calcium currents which were present in 25% of medium-sized cells from control animals. Altered Ca(2+) signalling in injured sensory neurons may contribute to hyperexcitability leading to neuropathic pain.
Hogan
Q H
QH
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA. qhogan@mcw.edu
McCallum
J B
JB
Sarantopoulos
C
C
Aason
M
M
Mynlieff
M
M
Kwok
W M
WM
Bosnjak
Z J
ZJ
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D020865:Calcium Channels, P-Type / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002452:Cell Count; D002462:Cell Membrane / Q000378:metabolism; D002469:Cell Separation; D048429:Cell Size; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009475:Neurons, Afferent / Q000378:metabolism* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D051381:Rats; D020426:Sciatic Neuropathy / Q000378:metabolism* / Q000473:pathology / Q000523:psychology
D020865:Calcium Channels, P-Type