title: [Pathophysiology of pain].
abstract: Progress in the knowledge of the pathophysiology of pain allow to associate clinical symptoms of painful syndroms to physiological, morphological and neurobiochemical changes observed both at peripheral and central sites. Thus, nociceptive pains involve both a sensitisation of nociceptors and a secondary central sensitisation. Numerous mediators are involved in these phenomena which reflect neuroplasticity. Peripherally, they come from plasma, immune cells and afferent fibres involved in neurogenic inflammation. Their number explains how the peripheral mechanisms of pain are complex and how it is difficult to pharmacologically suppress the activity of nociceptors. Other mediators are involved in the dorsal horn of the spinal cord. Excitatory amino acids are particularly involved by acting on NMDA receptors; substance P seems to work as a facilitatory neuromodulator rather than as a neurotransmitter. The mechanisms of neuropathic pains are different because both small and large diameter afferent fibers are involved. Ectopic discharges from lesional sites of C fibers, sprouting and abnormal neuronal connections have been described. Up regulation of ionic, especially sodic, channels has been demonstrated and could explain spontaneous discharges. Here again, central sensitisation is also observed but present knowledge does not allow to distinguish specific mechanisms. These progress in the knowledge of pathophysiology of pain allow to improve the understanding of the mechanism of action of analgesic drugs. They also give basis to the discovery of novel drugs with original mechanisms.
authors.affiliation: INSERM EPI 9904, Laboratoire de Pharmacologie Médicale, Faculté de Médecine-CHU, Clermont-Ferrand. alain.eschalier@u-clermont1.fr
authors.forename: A
authors.initials: A
authors.lastname: Eschalier
authors.forename: F
authors.initials: F
authors.lastname: Coudore
authors.forename: G
authors.initials: G
authors.lastname: Pickering
mesh_terms: D006801:Humans; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*