title: Systemic pregabalin attenuates facial hypersensitivity and noxious stimulus-evoked release of glutamate in medullary dorsal horn in a rodent model of trigeminal neuropathic pain.
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 1h 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.
authors: Alan Edwards Centre for Research on Pain, Dept. of Anesthesia, McGill University, Montreal, QC, Canada H3G 1Y6. naresh1@ualberta.ca
authors: Naresh
authors: N
authors: Kumar
authors: Pavel S
authors: PS
authors: Cherkas
authors: Vidya
authors: V
authors: Varathan
authors: Makiko
authors: M
authors: Miyamoto
authors: Chen Yu
authors: CY
authors: Chiang
authors: Jonathan O
authors: JO
authors: Dostrovsky
authors: Barry J
authors: BJ
authors: Sessle
authors: Terence J
authors: TJ
authors: Coderre
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003627:Data Interpretation, Statistical; D003782:Dental Pulp / Q000187:drug effects / Q000502:physiology; D005157:Facial Pain / Q000188:drug therapy*; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D020645:Mediodorsal Thalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D009149:Mustard Plant; D009437:Neuralgia / Q000188:drug therapy*; D010812:Physical Stimulation; D010938:Plant Oils; D000069583:Pregabalin; D051381:Rats; D017207:Rats, Sprague-Dawley; D014277:Trigeminal Neuralgia / Q000188:drug therapy*; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000700:Analgesics; D010938:Plant Oils; D018698:Glutamic Acid; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; C027793:mustard oil