Biologia, Bratislava 54/Suppl. 6: 11-19, 1999.

ISSN 0006-3088 (Biologia). ISSN 1335-6399 (Biologia. Section Cellular and Molecular Biology).

 

Review

Spinal pharmacology and the regulation of pain processing.

 

Tony L. Yaksh

Department of Anesthesiology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0818 USA; tel.: ++1 619 543 3597, fax: ++1 619 543 6070, email: tyaksh@ucsd.edu

* corresponding author

Received: July 30, 1999 / Accepted: October 5, 1999

 

Abstract

This review, written in honor of Jozef Marsala, emphasizes the complexity of spinal circuitry and pharmacology in nociceptive processing. Functionally, pain states can be generated i) by acute activation of high threshold afferents, ii) by tissue injury that leads to a persistent afferent discharge and a central cascade (activation of glutamatergic and neurokinin receptors; release of proexcitatory agents such as prostaglandins and nitric oxide; phosphorylation of membrane receptors and upregulation of membrane and cytosolic receptors and enzymes) and iii) nerve injury that leads to trophic changes (central and peripheral sprouting, cell death leading to loss of central inhibition and up regulation of receptors/ionophores and channels). Three important points are that i) the trophic changes observed after tissue and nerve injury serve to augment the processing of nociceptive information, ii) that these changes occur at the spinal level and iii) that these spinal changes are relevant to pain behavior, leading to behaviorally defined hyperalgesia and allodynia. Investigation of these spinally-mediated changes evoked by acute afferent input and tissue and nerve injury has revealed a rich pharmacology that can be directly addressed using spinally administered agents in well defined animal models. The observations accruing from such investigations have directly led to the implementation of such drug delivery for use in human pain states. Thus, agonists such as those for the , ∂ and K opiate, a2 adrenergic and Adenosine A-1 receptors, inhibitors of acetylcholinesterase and cyclooxygenase and blockers of the NMDA (N-methyl-D-aspartate) ionophore and the N-type calcium channel have been shown to diminish certain facilitated states after spinal delivery in preclinical models and then subsequently shown to be active in human pain states. These observations provide convergent data indicating that spinal mechanisms defined in preclinical models apply as well to human pain states and that the preclinical models can be usefully employed to predict clinical activity.

 

Key words: spinal cord, nociception, opiates, prostaglandins, nitric oxide.