Sensitization of meningeal nociceptors: inhibition by naproxen
- 1 February 2008
- journal article
- Published by Wiley in European Journal of Neuroscience
- Vol. 27 (4), 917-922
- https://doi.org/10.1111/j.1460-9568.2008.06068.x
Abstract
Migraine attacks associated with throbbing (manifestation of peripheral sensitization) and cutaneous allodynia (manifestation of central sensitization) are readily terminated by intravenous administration of a non‐selective cyclooxygenase (COX) inhibitor. Evidence that sensitization of rat central trigeminovascular neurons was also terminated in vivo by non‐selective COX inhibition has led us to propose that COX inhibitors may act centrally in the dorsal horn. In the present study, we examined whether COX inhibition can also suppress peripheral sensitization in meningeal nociceptors. Using single‐unit recording in the trigeminal ganglion in vivo, we found that intravenous infusion of naproxen, a non‐selective COX inhibitor, reversed measures of sensitization induced in meningeal nociceptors by prior exposure of the dura to inflammatory soup (IS): ongoing activity of Aδ‐ and C‐units and their response magnitude to mechanical stimulation of the dura, which were enhanced after IS, returned to baseline after naproxen infusion. Topical application of naproxen or the selective COX‐2 inhibitor N‐[2‐(cyclohexyloxy)‐4‐nitrophenyl]‐methanesulfonamide (NS‐398) onto the dural receptive field of Aδ‐ and C‐unit nociceptors also reversed the neuronal hyper‐responsiveness to mechanical stimulation of the dura. The findings suggest that local COX activity in the dura could mediate the peripheral sensitization that underlies migraine headache.Keywords
This publication has 24 references indexed in Scilit:
- Sensitization of central trigeminovascular neurons: Blockade by intravenous naproxen infusionNeuroscience, 2007
- Bradykinin-induced nociceptor sensitisation to heat depends on cox-1 and cox-2 in isolated rat skinPain, 2007
- Comparative Effects of the Nonsteroidal Anti-inflammatory Drug Nepafenac on Corneal Sensory Nerve Fibers Responding to Chemical IrritationInvestigative Ophthalmology & Visual Science, 2007
- Analgesic strategies beyond the inhibition of cyclooxygenasesTrends in Pharmacological Sciences, 2006
- Calcitonin gene–related peptide does not excite or sensitize meningeal nociceptors: Implications for the pathophysiology of migraineAnnals of Neurology, 2005
- Terminating Migraine With Allodynia and Ongoing Central Sensitization Using Parenteral Administration of COX1/COX2 InhibitorsHeadache: The Journal of Head and Face Pain, 2005
- Defeating migraine pain with triptans: A race against the development of cutaneous allodyniaAnnals of Neurology, 2003
- Acetylsalicylic acid inhibits meningeal nociception in ratPain, 1999
- Sensitization of meningeal sensory neurons and the origin of headachesNature, 1996
- Pain due to experimental acidosis in human skin: evidence for non-adapting nociceptor excitationNeuroscience Letters, 1995