Neuron–Glia Signaling in Trigeminal Ganglion: Implications for Migraine Pathology

摘要: Migraine is a chronic, painful, neurovascular disorder that affects an estimated 12% of the population.1 Sensitization and activation trigeminal ganglion nerves are thought to play central role in underlying pathology migraine other orofacial diseases.2,3 The nerve consists 3 main branches, ophthalmic (V1), maxillary (V2), mandibular (V3), each providing somatosensory innervation distinct regions head, face, cavity. Adult neurons exhibit pseudounipolar morphology characterized by single axon divides into peripheral branch.4 Activation trigeminovascular afferents V1 meninges releases calcitonin gene-related peptide (CGRP), which mediates neurogenic vasodilation, while efferent release CGRP contributes pain, sensitization, allodynia associated with migraine.5,6 Hyperalgesia likely involve both sensitization.7-9 Peripheral result increased activity nociceptors, initiate attack, involves enhanced excitability second-order neurons, leads pain.10 While importance sensitization has become clearer, not well understood. neuronal lowering threshold for activation. Glia cells, were serve only supportive role, now known directly modulate function activity.11,12 Interestingly, neuron–glia interactions have been shown be involved all stages inflammation pain several CNS diseases.13,14 Trigeminal ganglia comprise cells 2 types glial satellite Schwann associate fibers produce myelin.15 cell bodies primary afferent convey sensory information from periphery nervous system (CNS) completely surrounded form distinct, functional units. Morphological studies flattening processes lie close proximity plasma membrane cells. It accepted outnumber 10 1 ganglia, influence controlling microenvironment ganglion.12,16 communication between can occur via gap junctions or diffusible chemical messengers, mechanisms neuronal–glial communicate under basal inflammatory conditions known. In this study we used vivo model glia-enriched cultures investigate signaling within ganglion. Data our dye-coupling experiments demonstrated neuron glia occurring through response stimuli. To knowledge, first report type In addition, stimulation located V3 region caused rapid increase expression proteins S100B p38 mitogen-activated protein (MAP) kinase Somewhat surprisingly, was also observed V2 regions. Thus, one branch sustained example intraganglion communication. Furthermore, showed CGRP, released bodies, stimulate cytokines. Based on results, propose key migraine, rhinitis, temporomandibular joint (TMJ) disorders data may help explain commonly reported symptoms comorbid important implications further understanding therapy.