Sensibilisation nociceptive centrale : systèmes de signalisation cellulaire et moléculaire

Central nociceptive sensitization develops in response to repeated intense noxious stimulus, prolonged peripheral inflammation or nerve injury. This phenomenon is a reflection of central nervous system adaptive response in terms of neuronal plasticity and morphological as well as functional changes of other, non-neuronal, cell populations (especially glial cells). Increases of neuronal excitability, reinforcement of synaptic transmission efficacy and reduced inhibitory systems function result in a global gain of the nociceptive system responsiveness that characterizes the nociceptive sensitization. The emergence of central nociceptive sensitization in both physiological and pathological pain share some common mechanisms. However, the nociceptive sensitization related to pathological pain is long lasting and is associated with profound upsetting of inter- and intra-cellular signaling. These alterations involve many cell membrane receptors, various intracellular transduction pathways and lead to the modification of gene expression. The sustained change of cell phenotypes, triggered by differential gene expression, plays a key role in the maintenance of central nociceptive sensitization. Beyond the “classical” intervention of transcription factors, several alternative mechanisms of gene expression control were identified. Increasing number of reports support the role of these regulatory mechanisms, implicating non-coding micro RNA, non-coding long RNA or epigenetic modifications, in the pathogenesis of chronic pain. These exciting data also suggest that some of these regulatory systems could be probably exploited for the development of new therapeutic approaches.