Control Descendente Del Dolor

Progress in Neurobiology 66 (2002) 355–474

Descending control of pain
Mark J. Millan∗
Department of Psychopharmacology, Institut de Recherches Servier, 125 Chemin de Ronde, 78290 Croissy/Seine, Paris, France Received 11 November 2001; accepted 7 February 2002

Abstract Upon receipt in the dorsal horn (DH) of the spinal cord, nociceptive (pain-signalling) information from the viscera, skinand other organs is subject to extensive processing by a diversity of mechanisms, certain of which enhance, and certain of which inhibit, its transfer to higher centres. In this regard, a network of descending pathways projecting from cerebral structures to the DH plays a complex and crucial role. Specific centrifugal pathways either suppress (descending inhibition) or potentiate (descendingfacilitation) passage of nociceptive messages to the brain. Engagement of descending inhibition by the opioid analgesic, morphine, fulfils an important role in its pain-relieving properties, while induction of analgesia by the adrenergic agonist, clonidine, reflects actions at 2 -adrenoceptors ( 2 -ARs) in the DH normally recruited by descending pathways. However, opioids and adrenergic agents exploit buta tiny fraction of the vast panoply of mechanisms now known to be involved in the induction and/or expression of descending controls. For example, no drug interfering with descending facilitation is currently available for clinical use. The present review focuses on: (1) the organisation of descending pathways and their pathophysiological significance; (2) the role of individual transmitters andspecific receptor types in the modulation and expression of mechanisms of descending inhibition and facilitation and (3) the advantages and limitations of established and innovative analgesic strategies which act by manipulation of descending controls. Knowledge of descending pathways has increased exponentially in recent years, so this is an opportune moment to survey their operation andtherapeutic relevance to the improved management of pain. © 2002 Published by Elsevier Science Ltd.

Contents
1. General introduction: scope and aims of review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359 2. Organisation of descending input to the DH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3602.1. Relationship of descending pathways to primary afferent fibres and intrinsic DH neurones . . . 360 2.1.1. Neuronal circuitry in the DH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 360 2.1.2. Multiple roles of transmitters in descending pathways: inhibition and facilitation . . . . . 360 2.2. Preferential modulation by descendingpathways of nociceptive as compared to non-nociceptive information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362 2.3. Role of volume transmission in the actions of descending pathways . . . . . . . . . . . . . . . . . . . . . . . 364 2.4. Interactions of descending pathways with glial andimmunocompetent cells . . . . . . . . . . . . . . . . 364 2.5. Actions of descending pathways in spinal cord regions other than the DH . . . . . . . . . . . . . . . . . . 365 2.5.1. Modulation of autonomic (sympathetic and parasympathetic) outflow . . . . . . . . . . . . . . . . 365 2.5.2. Modulation of motor function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . 365
Abbreviations: 5-HT, serotonin; 2 -AR, 2 -adrenoceptor; AC, adenylyl cyclase; ACh, acetylcholine; AMPA, -amino-2,3-dihydro-5-methyl-3-oxo-4isoxazolepropanoic acid; ATP, adenosine triphosphate; CB, cannabinoid; CCK, cholecystokinin; CGRP, calcitonin gene related peptide; DA, dopamine; DF, descending facilitation; DH, dorsal horn; DI, descending inhibition; DRG, dorsal root...