Painful neuropathy decreases membrane calcium current in mammalian primaryafferent neurons

Hyperexcitability of the primary afferent neuron leads to neuropathic pain following injury to peripheral axons. Changes in calcium channel function o f sensory neurons following injury have not been directly examined at the c hannel level, even though calcium is a primary second messenger-regulating neuronal function. We compared calcium currents (I-Ca) in 101 acutely isola ted dorsal root ganglion neurons from 31 rats with neuropathic pain followi ng 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 t he CCI site. Membrane function was determined using patch-clamp techniques in current clamp mode, and in voltage-clamp mode using solutions and condit ions designed to isolate I-Ca. Somata of peripheral sensory neurons from hy peralgesic rats demonstrated decreased I-Ca. Peak calcium channel current d ensity was diminished by injury from 3.06 +/- 0.30 pS/pF to 2.22 +/- 0.26 p S/pF in medium neurons, and from 3.93 +/- 0.38 pS/ pF to 2.99 +/- 0.40 pS/p F in large neurons. Under these voltage and pharmacologic conditions, mediu m-sized neuropathic cells lacked obvious T-type calcium currents which were present in 25% of medium-sized cells from control animals. Altered Ca2+ si gnalling in injured sensory neurons may contribute to hyperexcitability lea ding to neuropathic pain. (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.