Restoration of calcium influx corrects membrane hyperexcitability in injured rat dorsal root ganglion neurons

Anesth Analg. 2008 Sep;107(3):1045-51. doi: 10.1213/ane.0b013e31817bd1f0.


Background: We have previously shown that a decrease of inward Ca(2+) flux (I(Ca)) across the sensory neuron plasmalemma, such as happens after axotomy, increases neuronal excitability. From this, we predicted that increasing I(Ca) in injured neurons should correct their hyperexcitability.

Methods: The influence of increased or decreased I(Ca) upon membrane biophysical variables and excitability was determined during recording from A-type neurons in nondissociated dorsal root ganglia after spinal nerve ligation using an intracellular recording technique.

Results: When the bath Ca(2+) level was increased to promote I(Ca), the after-hyperpolarization was decreased and repetitive firing was suppressed, which also followed amplification of Ca(2+)-activated K(+) current with selective agents NS1619 and NS309. A decreased external bath Ca(2+) concentration had the opposite effects, similar to previous observations in uninjured neurons.

Conclusions: These findings indicate that at least a part of the hyperexcitability of somatic sensory neurons after axotomy is attributable to diminished inward Ca(2+) flux, and that measures to restore I(Ca) may potentially be therapeutic for painful peripheral neuropathy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavior, Animal
  • Benzimidazoles / pharmacology
  • Calcium / chemistry
  • Calcium / metabolism*
  • Ganglia, Spinal / embryology*
  • Indoles / pharmacology
  • Male
  • Models, Biological
  • Neurons / metabolism*
  • Neurons, Afferent / metabolism
  • Oximes / pharmacology
  • Potassium / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Nerves / pathology


  • 6,7-dichloro-1H-indole-2,3-dione 3-oxime
  • Benzimidazoles
  • Indoles
  • Oximes
  • NS 1619
  • Potassium
  • Calcium