Role of calcitonin gene-related peptide and brain natriuretic peptide to modulate the excitability state of trigeminal neurons: relevance to migraine pathology and treatment

摘要: Hyperactivity of trigeminal sensory neurons is a major process to generate recurrent headache, typical migraine attacks. How physiological nociception converted into strong pathological pain remains, however, poorly understood. In recent years, certain neuropeptides and their receptors have been shown modulate neuron contribute the persistent hyperalgesia due stimulus sensitization that defines clinical experience chronic syndromes, including migraine. Using calcitonin gene-related peptide (CGRP) brain natriuretic (BNP) as examples, this review addresses mechanisms through which might nociceptor activity. One attractive notion signaling by potently regulated ambient levels these peptides: CGRP thought facilitate neuronal firing responsible for sensitiza - tion necessary trigger whereas BNP proposed act negative regulator For either peptide, key target appears be ATP-gated P2X3 receptor that, widely expressed neurons, generates fast, large excitation release glutamate onto second-order neurons. The fine balance between activities peptides suggested ultimately determine whether perceived at higher center or response. Hence, goal antagonism using pharmacological blockers monoclonal antibodies (to sequester directly inhibit its receptor) currently considered novel approach prophylaxis treat acute headache