Modulation of meningeal nociceptors mechanosensitivity by peripheral proteinase-activated receptor-2: the role of mast cells.
Inflammatory-related activation and sensitization of meningeal nociceptors is believed to play a key role in promoting the intracranial throbbing pain of migraine. We have shown recently that mast cell activation and various mast cell-derived inflammatory mediators can promote activation and sensitization of meningeal nociceptors. Mast cell tryptase has also been proposed to promote pain hypersensitivity by activating the proteinase-activated receptor 2 (PAR2) that is expressed on nociceptive neurons. In this study using in vivo single-unit recording in the trigeminal ganglion of anaesthetized rats, we found that local meningeal activation of PAR2 using the specific agonist SLIGRL-NH2 promoted sensitization of the threshold response while provoking desensitization of the suprathreshold responses. SLIGRL-NH2 also excited a subpopulation of meningeal nociceptors. Chronic mast cell depletion enhanced the sensitizing effects of PAR2 activation while curbing its desensitizing effects. Mast cell depletion did not change the PAR2-mediated excitatory effect. We propose that by enhancing the mechanical sensitivity of meningeal nociceptors local PAR2 activation could play a role in promoting the throbbing pain of migraine and that local mast cell degranulation may modulate such an effect.
Zhang
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Department of Anaesthesia, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
Levy
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D
D000818:Animals; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008578:Meninges / Q000378:metabolism*; D009619:Nociceptors / Q000378:metabolism*; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D044464:Receptor, PAR-2 / Q000378:metabolism*
D044464:Receptor, PAR-2