title: The role of chemosensitive afferent nerves and TRP ion channels in the pathomechanism of headaches.
abstract: The involvement of trigeminovascular afferent nerves in the pathomechanism of primary headaches is well established, but a pivotal role of a particular class of primary sensory neurons has not been advocated. This review focuses on the evidence that supports the critical involvement of transient receptor potential (TRP) channels in the pathophysiology of primary headaches, in particular, migraine. Transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1 receptors sensitive to vanilloids and other irritants are localized on chemosensitive afferent nerves, and they are involved in meningeal nociceptive and vascular responses involving neurogenic dural vasodilatation and plasma extravasation. The concept of the trigeminal nocisensor complex is put forward which involves the trigeminal chemosensitive afferent fibers/neurons equipped with specific nocisensor molecules, the elements of the meningeal microcirculatory system, and the dural mast cells. It is suggested that the activation level of this complex may explain some of the specific features of migraine headache. Pharmacological modulation of TRP channel function may offer a novel approach to the management of head pain, in particular, migraine.
authors.affiliation: Department of Physiology, University of Szeged, Dóm tér 10., 6720, Szeged, Hungary. dux.maria@med.u-szeged.hu
authors.forename: Mária
authors.initials: M
authors.lastname: Dux
authors.forename: Péter
authors.initials: P
authors.lastname: Sántha
authors.forename: Gábor
authors.initials: G
authors.lastname: Jancsó
mesh_terms: D000344:Afferent Pathways / Q000503:physiopathology; D015220:Calcium Channels / Q000378:metabolism*; D004388:Dura Mater / Q000503:physiopathology; D006801:Humans; D008881:Migraine Disorders / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009619:Nociceptors / Q000378:metabolism*; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000378:metabolism*; D050051:Transient Receptor Potential Channels / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000503:physiopathology; D014276:Trigeminal Nerve / Q000503:physiopathology
chemical_list: D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050916:TRPV Cation Channels; D050051:Transient Receptor Potential Channels