• Quinn H Hogan.
• Department of Anesthesiology, Medical College of Wisconsin, Room M4280, 8701 Watertown Plank Rd, Milwaukee, WI, USA. qhogan@mcw.edu
• Croat. Med. J. 2007 Feb 1;48(1):9-21.

AbstractThe pathogenesis of neuropathic pain is incompletely understood and treatments are often inadequate. Cytoplasmic Ca(2+) regulates numerous cellular processes in neurons. This review therefore examines the pathogenic contribution of altered inward Ca(2+) flux (I(Ca)) through voltage-gated Ca(2+) channels in sensory neurons after peripheral nerve injury. We reviewed studies that recorded membrane currents through intracellular and patch-clamp techniques, as well as intracellular Ca(2+) levels using fluorimetric indicators, and performed behavioral analysis of rodent nerve injury models. Following nerve injury by partial ligation, a response characterized by sustained lifting, shaking, and licking of the paw after sharp mechanical stimulation is a reliable indicator or neuropathic pain. Primary sensory neurons isolated from animals with this behavior show a decrease in high-voltage activated I(Ca) by approximately one third. Low voltage-activated I(Ca) is nearly eliminated by peripheral nerve injury. Loss of I(Ca) leads to decreased activation of Ca(2+)-activated K(+) currents, which are also directly reduced in traumatized neurons. As a result of these changes in membrane currents, membrane voltage recordings show increased action potential duration and diminished afterhyperpolarization. Excitability is elevated, as indicated by resting membrane potential depolarization and a decreased current threshold for action potential initiation. Traumatized nociceptive neurons develop increased repetitive firing during sustained depolarization after axotomy. Concurrently, cytoplasmic Ca(2+) transients are diminished. In conclusions, axotomized neurons, especially pain-conducting ones, develop instability and elevated excitability after peripheral injury. Treatment of neuronal I(Ca) loss at the level of injury of the dorsal root ganglion may provide a novel therapeutic pathway.

22 keywords...

hide…