Effects of antagonists to high-threshold calcium channels upon spinal mechanisms of pain, hyperalgesia and allodynia.

Abstract

High-threshold voltage-dependent calcium channels enable calcium ions to enter neurons upon depolarization and thereby influence synaptic mediator/receptor systems, membrane excitability levels, second and third messenger concentration, and gene expression. These phenomena underlie several processes including those of normal nociception and of hyperalgesia and allodynia. The present article deals with the role of spinal L-, N- and P/Q-type calcium channels in short-lasting nociception as well as in the hyperalgesia and allodynia elicited by chemical irritants of peripheral nociceptors, inflammatory and mechanical lesions of peripheral tissues, and lesions of peripheral nerves. The studies summarized herein are based on the spinal delivery of specific antagonists to high-threshold calcium channels, and reveal that blockade of L-type, P/Q-type and, particularly, N-type channels can prevent, attenuate, or both, subjective pain as well as primary and/or secondary hyperalgesia and allodynia in a variety of experimental and clinical conditions.