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The gap junction blocker carbenoxolone attenuates nociceptive behavior and medullary dorsal horn central sensitization induced by partial infraorbital nerve transection in rats

Wang, Huaa; Cao, Yea; Chiang, Chen-Yua; Dostrovsky, Jonathan O.a,b; Sessle, Barry J.a,b,*

doi: 10.1016/j.pain.2013.11.004
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Summary The gap junction blocker carbenoxolone attenuated nociceptive behavior and central sensitization of medullary dorsal horn nociceptive neurons induced by partial infraorbital nerve transection in rats.

ABSTRACT Glial cells are being increasingly implicated in mechanisms underlying pathological pain, and recent studies suggest glial gap junctions involving astrocytes may contribute. The aim of this study was to examine the effect of a gap junction blocker, carbenoxolone (CBX), on medullary dorsal horn (MDH) nociceptive neuronal properties and facial mechanical nociceptive behavior in a rat trigeminal neuropathic pain model involving partial transection of the infraorbital nerve (p-IONX). p-IONX produced facial mechanical hypersensitivity reflected in significantly reduced head withdrawal thresholds that lasted for more than 3 weeks. p-IONX also produced central sensitization in MDH nociceptive neurons that was reflected in significantly increased receptive field size, reduction of mechanical activation threshold, and increases in noxious stimulation-evoked responses. Intrathecal CBX treatment significantly attenuated the p-IONX–induced mechanical hypersensitivity and the MDH central sensitization parameters, compared to intrathecal vehicle treatment. These results provide the first documentation that gap junctions may be critically involved in orofacial neuropathic pain mechanisms.

aDepartment of Oral Physiology, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada

bDepartment of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

* Corresponding author. Address: Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, ON M5G 1G6, Canada. Tel.: +1 416 979 4910; fax: +1 416 979 4936.

E-mail address:barry.sessle@utoronto.ca

Article history:

Received 22 May 2013

Received in revised form 1 November 2013

Accepted 6 November 2013

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

© 2014 International Association for the Study of Pain
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