Dural afferents express acid-sensing ion channels: a role for decreased meningeal pH in migraine headache.
Dural afferents express acid-sensing ion channels: a role for decreased meningeal pH in migraine headache.
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DOI：
10.1016/j.pain.2010.09.036
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发表时间：
2011-01
期刊：
影响因子：
7.4
通讯作者：
Dussor G
中科院分区：
文献类型：
--
作者：
Yan J;Edelmayer RM;Wei X;De Felice M;Porreca F;Dussor G
Migraine headache is one of the most common neurological disorders. The pathological conditions that directly initiate afferent pain signaling are poorly understood. In trigeminal neurons retrogradely labeled from the cranial meninges, we have recorded pH-evoked currents using whole-cell patch-clamp electrophysiology. Approximately 80% of dural afferent neurons responded to a pH 6.0 application with a rapidly activating and rapidly desensitizing ASIC-like current that often exceeded 20 nA in amplitude. Inward currents were observed in response to a wide range of pH values and 30% of the neurons exhibited inward currents at pH 7.1. These currents led to action potentials in 53%, 30% and 7% of the dural afferents at pH 6.8, 6.9 and 7.0, respectively. Small decreases in extracellular pH were also able to generate sustained window currents and sustained membrane depolarizations. Amiloride, a non specific blocker of ASIC channels, inhibited the peak currents evoked upon application of decreased pH while no inhibition was observed upon application of TRPV1 antagonists. The desensitization time constants of pH 6.0-evoked currents in the majority of dural afferents was less than 500 ms which is consistent with that reported for ASIC3 homomeric or heteromeric channels. Finally, application of pH 5.0 synthetic-interstitial fluid to the dura produced significant decreases in facial and hind-paw withdrawal threshold, an effect blocked by amiloride but not TRPV1 antagonists, suggesting that ASIC activation produces migraine-related behavior in vivo. These data provide a cellular mechanism by which decreased pH in the meninges following ischemic or inflammatory events directly excites afferent pain-sensing neurons potentially contributing to migraine headache.
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影响因子：
4.9
作者：
LAMBERT, GA;MICHALICEK, J
通讯作者：
MICHALICEK, J
影响因子：
2.9
作者：
Rozniecki, JJ;Dimitriadou, V;Theoharides, TC
通讯作者：
Theoharides, TC
影响因子：
11.2
作者：
De Felice M;Ossipov MH;Wang R;Lai J;Chichorro J;Meng I;Dodick DW;Vanderah TW;Dussor G;Porreca F
通讯作者：
Porreca F
影响因子：
11.2
作者：
Edelmayer, Rebecca M.;Vanderah, Todd W.;Majuta, Lisa;Zhang, En-Tan;Fioravanti, Beatriz;De Felice, Milena;Chichorro, Juliana G.;Ossipov, Michael H.;King, Tamara;Lai, Josephine;Kori, Shashi H.;Nelsen, Andrew C.;Cannon, Keri E.;Heinricher, Mary M.;Porreca, Frank
通讯作者：
Porreca, Frank
DOI：
10.1073/pnas.011404498
发表时间：
2001-01-16
影响因子：
11.1
作者：
Sutherland, SP;Benson, CJ;McCleskey, EW
通讯作者：
McCleskey, EW