Izvorni znanstveni članak
Role of Decreased Sensory Neuron Membrane Calcium Currents in the Genesis of Neuropathic Pain
Quinn H. Hogan
Sažetak
Aim: The pathogenesis of neuropathic pain is incompletely understood and treatments are often inadequate. Cytoplasmic Ca2+ regulates numerous cellular processes in neurons. This review therefore examines the pathogenic contribution of altered inward Ca2+ flux (ICa) through voltage-gated Ca2+ channels in sensory neurons after peripheral nerve injury.
Methods: Studies are considered that have recorded membrane currents through intracellular and patch-clamp techniques, intracellular Ca2+ levels using fluorimetric indicators, and behavioral analysis of rodent nerve injury models. A synthesis is offered to incorporate various observations.
Results: 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 ICa by approximately one third. Low voltage-activated ICa is nearly eliminated by peripheral nerve injury. Loss of ICa leads to decreased activation of Ca2+-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 AP initiation. Traumatized nociceptive neurons develop increased repetitive firing during sustained depolarization after axotomy. Concurrently, cytoplasmic Ca2+ transients are diminished.
Ključne riječi
Currents; Decreased; Neuropathic Pain
Hrčak ID:
9350
URI
Datum izdavanja:
20.2.2007.
Posjeta: 1.322 *