title: Modulation of intracranial meningeal nociceptor activity by cortical spreading depression: a reassessment.
abstract: Cortical spreading depression (CSD), a putative migraine trigger, has been shown recently to promote multiple activation patterns of meningeal nociceptors. In the current study we used a modified experimental approach in a rat model to: 1) reassess the responses of meningeal nociceptors following a single CSD episode, 2) examine factors that may influence the propensity of meningeal nociceptors to develop a prolonged activation following a CSD, and 3) test the responses of meningeal nociceptors following multiple CSDs. A single CSD episode promoted persistent activation in about 50% of the nociceptors tested, similar to our previous report. Only two patterns of prolonged nociceptor activation were observed: biphasic activation and one with a delayed onset. Aδ units had shorter mean onset latency for the prolonged activation than C units. The prolonged activation onset latency was inversely correlated with the number of the nociceptors' receptive fields. The propensity to develop the prolonged activation following CSD was related to the presence of basal ongoing activity, but neither to the emergence of brief activation during the CSD phase nor to the nociceptors' responsiveness to inflammatory mediators or ATP. Finally, multiple CSDs did not promote a heightened nociceptive response compared with a single CSD. The present study confirms the ability of a single CSD to elicit persistent activation of meningeal nociceptors. CSD-evoked prolonged nociceptive responses may not be related to the inflammatory and ATP chemosensitivity of the neurons but rather to other neuronal properties, such as basal ongoing activity and number of receptive fields.
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts dlevy1@bidmc.harvard.edu.
authors.forename: Dan
authors.initials: D
authors.lastname: Levy
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000502:physiology; D013181:Cortical Spreading Depression / Q000502:physiology*; D008297:Male; D008578:Meninges / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D059225:Nociception / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: CSD; in vivo electrophysiology; meningeal nociceptors; migraine headache