Faculty Collaboration Database

Loss of T-type calcium current in sensory neurons of rats with neuropathic pain. Anesthesiology 2003 Jan;98(1):209-16

Date

12/28/2002

Pubmed ID

12502999

DOI

10.1097/00000542-200301000-00032

Scopus ID

2-s2.0-0037217589 (requires institutional sign-in at Scopus site)   70 Citations

Abstract

BACKGROUND: Pathophysiology in the primary sensory neuron may contribute to chronic neuropathic pain. Ca channels play a central role in neuronal processes, and sensory neurons are rich in low-voltage-activated calcium channels (LVACCs). However, the physiologic function of these channels is unknown. Their possible role in rebound burst firing makes them a candidate for increased excitability after neuropathic injury.

METHODS: This study uses pharmacological methods to isolate LVACC in cells from the dorsal root ganglia of neuropathic and sham-operated rats, including the blockade of high-voltage-activated Ca channels with fluoride and selective toxins. LVACCs were examined with conventional whole cell patch clamp electrophysiology techniques.

RESULTS: After chronic constriction injury of the peripheral axon, LVACC was significantly reduced compared to sham rats as shown by a 60% reduction in peak current density and an 80% reduction in total calcium influx. A depolarizing shift in the voltage dependence of activation and an increase in the rate of deactivation and inactivation appear to cause this reduction of LVACC. Either Ni2+ or mibefradil, blockers of LVACC, applied in the bath to normal dorsal root ganglion cells during current clamp significantly and reversibly increased excitability.

CONCLUSIONS: These results suggest that loss of LVACC may contribute to decreased spike frequency adaptation and increased excitability after injury to sensory neurons. Through decreased Ca2+ influx, the cell becomes less stable and more likely to initiate or transmit bursts of action potentials. Consequently, modulation of Ca2+ currents at the dorsal root ganglion may be a potential method of therapeutic intervention.

Author List

McCallum JB, Kwok WM, Mynlieff M, Bosnjak ZJ, Hogan QH

Authors

Quinn H. Hogan MD Professor in the Anesthesiology department at Medical College of Wisconsin
Wai-Meng Kwok PhD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Algorithms
Animals
Calcium Channels, T-Type
Cell Separation
Chronic Disease
Male
Membrane Potentials
Neurons, Afferent
Pain
Patch-Clamp Techniques
Peripheral Nervous System Diseases
Rats
Signal Transduction