The gap junction blocker carbenoxolone attenuates nociceptive behavior and medullary dorsal horn central sensitization 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 3weeks. 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.

Keywords: Carbenoxolone; Central sensitization; Gap junction; Infraorbital nerve; Medulla; Neuropathic pain.