Painful peripheral nerve injury decreases calcium current in axotomized sensory neurons.
BACKGROUND
Reports of Ca(2+) current I(Ca) loss after injury to peripheral sensory neurons do not discriminate between axotomized and spared neurons. The spinal nerve ligation model separates axotomized from spared neurons innervating the same site. The authors hypothesized that I(Ca) loss is a result of neuronal injury, so they compared axotomized L5 dorsal root ganglion neurons to spared L4 neurons, as well as neurons from rats undergoing skin incision alone.


METHODS
After behavioral testing, dissociated neurons from L4 and L5 dorsal root ganglia were studied in both current and voltage patch clamp modes. The biophysical consequence of I(Ca) loss on the action potential was confirmed using selective I(Ca) antagonists. Data were grouped into small, medium, and large cells for comparison.


RESULTS
Reduced I(Ca) was predominantly a consequence of axotomy (L5 after spinal nerve ligation) and was most evident in small and medium neurons. ICa losses were associated with action potential prolongation in small and medium cells, whereas the amplitude and duration of after hyperpolarization was reduced in medium and large neurons. Blockade with Ca(2+) channel antagonists showed that action potential prolongation and after hyperpolarization diminution were alike, attributable to the loss of I(Ca).


CONCLUSIONS
Axotomy is required for I(Ca) loss. I(Ca) loss correlated with changes in the biophysical properties of sensory neuron membranes during action potential generation, which were due to I(Ca) loss leading to decreased outward Ca(2+)-sensitive K currents. Taken together, these results suggest that neuropathic pain may be mediated, in part, by loss of I(Ca) and the cellular processes dependent on Ca(2+).
McCallum
J Bruce
JB
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, 53226, USA
Kwok
Wai-Meng
WM
Sapunar
Damir
D
Fuchs
Andreas
A
Hogan
Quinn H
QH
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D019771:Axotomy; D002118:Calcium / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000502:physiology*; D010523:Peripheral Nervous System Diseases / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002118:Calcium