• D Le Bars and F Adam.
• Inserm U-161, 2, rue d'Alésia, 75014 Paris, France.
• Ann Fr Anesth Reanim. 2002 Apr 1; 21 (4): 315-35.

ObjectiveTo bring together the most recent data concerning the physiology of nociceptors at a time when there has been significant progress in the understanding of these.Data SourcesReferences were obtained from computerised bibliographic data banks (Medline and others) and the authors' personal documents.Data SynthesisNociceptive impulses are generated at the periphery in unmyelinated fibres called nociceptors, the responses of which depend on the tissue environment. Numerous mediators can activate, sensitise or "wake up" nociceptor: kinins (bradykinin, kallidin and their metabolites), pro-inflammatory cytokines (TNF alpha, IL-6, IL-1 beta, IL-8), anti-inflammatory cytokines (IL-4, IL-6, IL-10, IL-12, IL-13), prostanoids (PGE2, PGI2), lipo-oxygenases (leucotrienes such LTB4 or 15-HETE), the "central mediators of the immune response" (NF-kappa B), growth factors such as neurotrophins (NGF, BDNF, NT-3 and NT-4/5), peptides (substance P, CGRP, Neurokinin A), nitric oxide, histamine, serotonin, proteases, excitatory amino acids, adrenergic amines and opioids. The release of neuromediators by primary afferent fibres in the spinal cord may be summarised by successively considering calcium channels, presynaptic receptors, excitatory amino acids and peptides.ConclusionSensitisation phenomena are not exclusively peripheral but also central in origin and these are interlinked.

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