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ANALGESIA

Restoration of Calcium Influx Corrects Membrane Hyperexcitability in Injured Rat Dorsal Root Ganglion Neurons

Quinn Hogan, MD^*, Philipp Lirk, MD^*, Mark Poroli, BS^*, Marcel Rigaud, MD^*, Andreas Fuchs, MD^*, Patrick Fillip, MD^*, Marko Ljubkovic, MD^*||, Geza Gemes, MD^*, and Damir Sapunar, MD, PhD^*||

From the *Department of Anesthesiology, Medical College of Wisconsin, Milwaukee Veterans Administration Medical Center, Milwaukee, Wisconsin; Department of Anesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria; Department of Intensive Care and Anesthesiology, Medical University of Graz, Graz, Austria; and ||University of Split Medical School, Split, Croatia.

Address correspondence and reprint requests to Quinn Hogan, MD, Department of Anesthesiology, MEB, Department of Anesthesiology, 8701 Watertown Plank Rd, Milwaukee, WI 53226. Address e-mail to qhogan{at}mcw.edu.

Abstract

BACKGROUND: We have previously shown that a decrease of inward Ca²⁺ 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 Ca²⁺ level was increased to promote I_Ca, the after-hyperpolarization was decreased and repetitive firing was suppressed, which also followed amplification of Ca²⁺-activated K⁺ current with selective agents NS1619 and NS309. A decreased external bath Ca²⁺ 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 Ca²⁺ flux, and that measures to restore I_Ca may potentially be therapeutic for painful peripheral neuropathy.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999