Physiopathologie de la sensibilisation centrale
The pathophysiology of central sensitization
Injury to peripheral tissues following trauma or surgery often results in hyperalgesia that is characterized by increased sensitivity to painful stimuli. Often innocuous stimuli such as light touch are perceived as painful. Until recently, it was thought that the increase in pain was due to changes at the site of injury. We now know that the increase in pain also involves central nervous system hyperexcitability leading to long-term changes in the nervous system. Animal models of hyperalgesia produced by tissue or nerve injury have been developed and mimic persistent pain conditions. After tissue injury, there is an increased sensitivity of nociceptors located in the injured zone. These changes in the periphery result in an increased neuronal barrage into the central nervous system and contribute to the increase in pain after injury. The increased neuronal barrage into the central nervous system (CNS) leads to hyperexcitability of CNS neurons, particularly at the level of the spinal dorsal horn. The hyperexcitability or central sensitization involves activation of excitatory amino acid and neuropeptide neurotransmitters and their receptors. Initially, activation of G-protein coupled receptors such as the metabotropic glutamate receptor and the Substance P receptor lead to release of calcium from intracellular stores and the phosphorylation of subunits of the N-methyl-D-aspartate (NMDA) receptor by calcium-dependent protein kinases. Susequent activation of the NMDA receptor leads to the influx of calcium into neurons and the further activation of protein kinases and phosphorylation of receptors. There are also changes in the gene expression of NMDA as well as other receptor subunits. The sum effect of these changes is an alteration in the sensitivity of receptors, increased excitability, and ultimately an amplification of pain. These changes are referred to as activity-dependent plasticity or central sensitization and appear to be most robust in response to deep tissue injury. The transmission of information in the CNS related to persistent tissue injury is modulated by descending control systems in the brain. These descending pathways are also subject to changes in excitability due to the persistent neuronal barrage. A similar form of activity-dependent plasticity occurs in brain stem descending pathways to complement the plasticity found at the level of the spinal cord. Under usual conditions, the net effect of the descending projections from brain stem sites to the spinal cord is a balance between descending facilitation and inhibition with inhibition predominating after persistent tissue injury. Under some conditions, this balance shifts to a net excitatory effect in which descending modulation results in more hyperexcitability and more pain after injury. In patients suffering from deep pain conditions, where central sensitization appears to be a prominent component, such as temporomandibular joint disorders, fibromyalgia and irritable bowel syndrome, the diffuse nature and amplification of pain, in part, may be due to this imbalance. These findings have functional implications relevant to the survival of an organism in response to the threat and presence of tissue injury. The problem of persistent pain can now be attacked at sites of activity-dependent plasticity where it is initiated and maintained.
Hyperalgésie, Algie, Neuropeptides, Récepteurs NMDA, Plasticité dépendante de l’activité, Inhibition descendante, Facilitation descendante, Troubles de l’articulation temporo-mandibulaire, Fibromyalgie, Syndrome du côlon irritable
Hyperalgesia, Pain, Neuropeptides, NMDA receptors, Activity-dependent plasticity, Descending inhibition, Descending facilitation, Temporomandibular joint disorders, Fibromyalgia, Irritable bowel syndrome