Pathophysiology of pain

Progress in the knowledge of the pathophysiology of pain allow to associate clinical symptoms of painful syndroms to physiological, morphological and neuro-biochemical changes observed both at peripheral and central sites. Th us, nociceptive pains involve both a sensitisation of nociceptors and a sec ondary central sensitisation. Numerous mediators are involved in these phen omena which reflect neuroplasticity. Peripherally, they come from plasma, i mmune cells and afferent fibres involved in neurogenic inflammation. Their number explains how the peripheral mechanisms of pain are complex and how i t is difficult to pharmacologically suppress the activity of nociceptors. O ther mediators are involved in the dorsal horn of the spinal cord. Excitato ry amino acids are particularly involved by acting on NMDA receptors ; subs tance P seems to work as a facilitatory neuromodulator rather than as a neu rotransmitter. The mechanisms of neuropathic pains are different because bo th small and large diameter afferent fibers are involved. Ectopic discharge s from lesional sites of C fibers, sprouting and abnormal neuronal connecti ons 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 all ow 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 discover of novel drugs with original mechanisms.