Regional Anesthesia and Pain Medicine Vol, 24 No. 3 May-June Supplement 1999
TITLE: Effects of lamotrigine on pain-induced chemo-somatosensory evoked potential.
AUTHORS: Jyrson G. Klamt, MD, Ph.D 1. and John Posner M.D., Ph.D2. ~FILIATION: ~Department of Surgery, Orthopedics and Traumatology. Faculty of Medicine of Ribeirio Preto- University of S~o Paulo. Ribeir~o Preto - SP. 14048-900. Brazil, 2Bios (Consultancy & Contract Research) Ltd. london. UK Introduction. Lamotrigine is a sodium channel blocker that inhibit selectively the neuronal release of glutamate (1). It has been shown to produce analgesia in acute and chronic pain models in rat without causing noticeable sedation (2) and to reduce the pain scores of volunteers assessed in the cold pain test after oral administration (3,4). The purpose of the present study was to determine the analgesic effect of oral lamotrigine in healthy volunteers using the ehemo-somatosensory evoked potential (CSSEP) (intranasal CO2 pain test). Methods. The study protocol was approved by the East Suffolk Health Authority District Medical Ethical Committee. Young health volunteers of either sex, aged 18-15 years and weight of at least 50 Kg participate in then experiment. A double blind, randomized, placebo-controlled crossover design was used. lntxanasal CO2 evoked potential and pain rating intensity (VAS-O= no pain and 10 = worst possible pain ) were measured before and after two hours of drug administration. According to a randomized code , 12 subjects received either lamotrigine (300rag) or lactose dummy given as matching capsules. The intranasal CO2 test was performed again 2 hours after treatment administrations. There was an interval of at least two weeks b~veen occasions. Ten painful stimuli (intranasal CO2 40 to 60% during 200 msec with inter-stimuli interval of 2 see) were delivered to nasal mucosa via left nostril during each session of approximately 20 minutes. Blood sample (5ml) was collected before each testing session for assay of plasma lamotrigine. The EEG was recorded from seven positions of the 10/20 system referenced to earlobe.(A1 + A2). Evoked potentials were recorded at CZ and PZ positions (0,16 - 70 HZ) were submitted to Fast Fourier Transformation and also average. The dependant variables were latency to peak N! and Pl00 (ms) and the amplitude between peaks N1 and P100 0xV). The data were subject to analysis of variance technique with subject, occasion and treatment used as factors. Results. Lamotrigine produced significantly higher latency to P~oo values at two hours post-drug than placebo (p<0,05) but no significant effects on the others parameters. The plasma concentration of lamotrigine was 5,6 _+0,7 l~g ml"I (mean + SD) Discussion. Oral lamotrigine did not exhibited analgesic property in the intranasal C02 pain model ~-~er~nc~s: 1. UptonN: Trends Pharmacol Sci 15:465-463, 1994. 2. Nakamura-Craig et al: Pain 63:33-36, 1995. 3. Hobbiger SF: Welleome Internal Document. 4. Webb J et al: Pain 76:357-363, 1998.