Calcitonin gene-related peptide does not excite or sensitize meningeal nociceptors: implications for the pathophysiology of migraine.
Migraine is among the most common types of pain, but its mechanisms are poorly understood. A growing body of evidence points to a critical role of calcitonin gene-related peptide (CGRP) in the pathophysiology of migraine headache. During migraine, CGRP is thought to be released from peripheral endings of perivascular meningeal nociceptors primary and to promote vasodilatation. A current hypothesis suggests that peripheral CGRP and its related meningeal vasodilatation results in activation and sensitization, leading to the generation of migraine headache. However, direct evidence supporting this idea is lacking. Here, using electrophysiological, extracellular, single-unit recording combined with laser-Doppler flowmetry measurements of dural blood flow (DBF), we examined whether CGRP and meningeal vasodilatation promote activation or sensitization of meningeal nociceptors. Changes in (DBF), ongoing discharge, and responsiveness to mechanical stimulation of the dura were studied after either topical administration or intravenous infusion of rat alpha-CGRP in anesthetized rats. Both topical and systemic administration of CGRP caused a significant increase in dural blood flow; however, neither method of CGRP administration resulted in activation or sensitization of meningeal nociceptors. The results of this study suggest that CGRP effects in the meninges, including meningeal vasodilatation, are not sufficient to activate or sensitize meningeal nociceptors.
Levy
Dan
D
Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA. dlevy1@bidmc.harvard.edu
Burstein
Rami
R
Strassman
Andrew M
AM
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D004195:Disease Models, Animal; D007839:Functional Laterality; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008297:Male; D008881:Migraine Disorders / Q000503:physiopathology*; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012684:Sensory Thresholds / Q000502:physiology; D013997:Time Factors; D012668:Trigeminal Ganglion / Q000503:physiopathology; D014665:Vasodilator Agents / Q000627:therapeutic use*
D014665:Vasodilator Agents; D015740:Calcitonin Gene-Related Peptide