Painful nerve injury decreases resting cytosolic calcium concentrations in sensory neurons of rats.
BACKGROUND
Neuropathic pain is difficult to treat and poorly understood at the cellular level. Although cytoplasmic calcium ([Ca]c) critically regulates neuronal function, the effects of peripheral nerve injury on resting sensory neuronal [Ca]c are unknown.


METHODS
Resting [Ca]c was determined by microfluorometry in Fura-2 AM-loaded neurons dissociated from dorsal root ganglia of animals with hyperalgesia to mechanical stimulation after spinal nerve ligation and section (SNL) at the fifth and sixth lumbar (L5 and L6) levels and from animals after skin incision alone (control group). Axotomized neurons from the L5 dorsal root ganglia were examined separately from adjacent L4 neurons that share the sciatic nerve with degenerating L5 fibers.


RESULTS
After SNL, large (34 mum or larger) neurons from the L4 ganglion showed a 29% decrease in resting [Ca]c, whereas those from the L5 ganglion showed a 54% decrease. Small neurons only showed an effect of injury in the axotomized L5 neurons, in which resting [Ca]c decreased by 30%. A decrease in resting [Ca]c was not seen in neurons isolated from rats in which hyperalgesia did not develop after SNL. In separate experiments, SNL reduced resting [Ca]c in capsaicin-insensitive neurons of the L5 ganglion by 60%, but there was no change in neurons from L4. Resting [Ca]c of capsaicin-sensitive neurons was not affected by injury in either ganglion. SNL injury decreased the proportion of neurons sensitive to capsaicin in the L5 group but increased the proportion in the L4 group.


CONCLUSIONS
Painful SNL nerve injury depresses resting [Ca]c in sensory neurons. This is most marked in axotomized neurons, especially the large and capsaicin-insensitive neurons presumed to transmit non-nociceptive sensory information.
Fuchs
Andreas
A
Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Lirk
Philipp
P
Stucky
Cheryl
C
Abram
Stephen E
SE
Hogan
Quinn H
QH
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002211:Capsaicin / Q000633:toxicity; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism*
D002211:Capsaicin; D002118:Calcium