J Neurophysiol 101: 3126-3134, 2009.
First published April 1, 2009; doi:10.1152/jn.91339.2008
0022-3077/09 $8.00
Electrophysiological Properties of Dural Afferents in the Absence and Presence of Inflammatory Mediators
Andrea M. Harriott1 and
Michael S. Gold2,3,4,5
1Department of Neural and Pain Sciences and Medical Sciences Training Program, University of Maryland at Baltimore, Baltimore, Maryland; and 2Department of Anesthesiology, 3Department of Medicine—Division of Gastroenterology, Hepatology, and Nutrition, 4Department of Neurobiology, and 5Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, Pennsylvania
Submitted 18 December 2008;
accepted in final form 23 March 2009
Migraine is a debilitating condition characterized by recurrent severe head pain. Although mechanisms underlying a migraine attack remain controversial, one proposal is that inflammatory mediator (IM)–induced activation and sensitization of dural afferents contribute to the initiation of migraine pain. We and others have shown that the electrophysiological properties of afferents, both in the absence and the presence of IM, vary as a function of target of innervation. These differences may account for unique aspects of pain syndromes associated with specific body regions. Therefore the purpose of the present study was to test the hypothesis that the electrophysiological properties of dural afferents differ from those innervating the temporalis muscle (TM), a structure in close proximity to the dura but that is not associated with pain syndromes at all similar to migraine. Acutely dissociated retrograde labeled primary afferents innervating the dura and TM were examined with whole cell current-clamp recordings. Passive and active electrophysiological properties were determined before and after the application of IM: (in µM) prostaglandin E2 (1), bradykinin (10), and histamine (1). In the absence of IM, there were significant differences between the two populations, particularly with respect to the response to suprathreshold stimulation where dural afferents were more excitable than TM afferents. Importantly, although both populations of afferents were sensitized by IM, the pattern of passive and active electrophysiological changes associated with IM-induced sensitization of these two populations of afferents suggested that there were both similarities and marked differences between the two with respect to underlying mechanisms of sensitization. If the differences between dural and TM afferents are due to a differential pattern of ion channel expression rather than differences in the relative density/biophysical properties of the same ion channels, it may be possible to selectively treat migraine pain by targeting the distinct mechanisms underlying IM-induced sensitization of dural afferents.
Address for reprint requests and other correspondence: M. S. Gold, Department of Anesthesiology, University of Pittsburgh, 200 Lothrop Street, Rm E1440 BST, Pittsburgh, PA 15213 (E-mail: msg22{at}pitt.edu)
Copyright © 2009 by the The American Physiological Society.
