Systemic pregabalin attenuates facial hypersensitivity and noxious stimulus-evoked release of glutamate in medullary dorsal horn in a rodent model of trigeminal neuropathic pain |
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Authors: | Naresh Kumar Pavel S Cherkas Vidya Varathan Makiko Miyamoto Chen Yu Chiang Jonathan O Dostrovsky Barry J Sessle Terence J Coderre |
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Institution: | 1. Alan Edwards Centre for Research on Pain, Dept. of Anesthesia, McGill University, Montreal, QC, Canada H3G 1Y6;2. Faculty of Dentistry, University of Toronto, Toronto, ON, Canada M5G 1G6;3. Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 1A1;4. School of Dentistry, Nihon University, Tokyo 101-8310, Japan |
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Abstract: | Pregabalin is effective in treating many neuropathic pain conditions. However, the mechanisms of its analgesic effects remain poorly understood. The aim of the present study was to determine whether pregabalin suppresses facial mechanical hypersensitivity and evoked glutamate release in the medullary dorsal horn (MDH) in a rodent model of trigeminal neuropathic pain. Nociceptive mechanical sensitivity was assessed pre-operatively, and then post-operatively 1 h following pregabalin or vehicle (saline) treatment on post-operative days 2 and 5 following infraorbital nerve transection (IONX). In addition, an in vivo microdialysis probe was inserted into the exposed medulla post-operatively and dialysate samples were collected. Glutamate release was then evoked by mustard oil (MO) application to the tooth pulp, and the effects of pregabalin or vehicle were examined on the MDH glutamate release. Glutamate concentrations in the dialysated samples were determined by HPLC, and data analyzed by ANOVA. IONX animals (but not control animals) showed facial mechanical hypersensitivity for several days post-operatively. In addition, tooth pulp stimulation with MO evoked a transient release of glutamate in the MDH of IONX animals. Compared to vehicle, administration of pregabalin significantly attenuated the facial mechanical hypersensitivity as well as the MO-evoked glutamate release in MDH. This study provides evidence in support of recent findings pointing to the usefulness of pregabalin in the treatment of orofacial neuropathic pain. |
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Keywords: | CSF cerebrospinal fluid HPLC high performance liquid chromatography i p intraperitoneal i v intravenous MDH medullary dorsal horn MO mustard oil IONX transection of the infraorbital nerve SEM standard error of the mean |
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