Comparative animal study of the antinociceptive efficacy of lamotrigine and gabapentin for the management of pain.

UNLABELLED: Pain relief using drugs with high efficacy provides significant improvement in the patients' lives. Drugs like lamotrigine (LTG) and gabapentin (GBP) have the ability to overcome the symptoms of neuropathic pain. AIM: The present study offers a comparative analysis of LTG and GBP efficacy in a rat model of nociceptive pain after single administration. METHOD: Sixty-three Wistar-Bratislava rats randomized into 7 groups were included: a control group treated with saline solution and 6 groups treated with different doses of LTG and GBP. Nociceptive responses to thermal and mechanical stimulations were evaluated before and after drug administration, at different time intervals, using paw pressure and hot plate tests. The obtained data were statistically analyzed, with significance at p value < 0.05. RESULTS: LTG 100 mg/kg and 50 mg/kg presented a significant analgesic effect in both mechanical and thermal tests, 1 and 2 hours after administration. GBP 100 mg/kg increased latency time in hot plate test. The effect of both anticonvulsant drugs occurred rapidly after administration, but had a short duration. CONCLUSIONS: LTG and GBP had an analgesic effect in a single dose administration. The effect of LTG was more evident since it was observed in both tests. Their effect was dose dependent.

Timing of elective repeat caesarean does matter: Importance of avoiding early-term delivery especially in diabetic patients.

Five hundred and three elective repeat caesarean sections were analysed to examine the impact of timing of delivery between 37 and 40 weeks' gestation on foetal and maternal short-term outcome. Gestational age, Apgar scores and admission to the neonatal intensive care unit (NICU)-based foetal outcome. Maternal complications were comparatively evaluated. Due to the increasing incidence of gestational diabetes a subgroup analysis on this issue was performed. Neonates born by elective repeat caesarean in early term had a 3.2 times increased risk of being admitted to the NICU due to foetal adaption disorders in the early post-natal phase. Overall maternal peri-operative risks were low and did not differ significantly between 37 and 41 weeks' gestation. Maternal gestational diabetes constituted an additional independent risk factor in early term. In summary, elective early-term caesarean delivery appears to negatively impact immediate neonatal outcome. Waiting at least until 38 completed weeks' gestation improves foetal outcome, especially in diabetic patients.

Influence of pulse sequence, polarity and amplitude on magnetic stimulation of human and porcine peripheral nerve.

1. Mammalian phrenic nerve, in a trough filled with saline, was excited by magnetic coil (MC)-induced stimuli at defined stimulation sites, including the negative-going first spatial derivative of the induced electric field along a straight nerve, at a bend in the nerve, and at a cut nerve ending. At all such sites, the largest amplitude response for a given stimulator output setting was elicited by an induced damped polyphasic pulse consisting of an initial quarter-cycle hyperpolarization followed by a half-cycle depolarization compared with a predominantly 'monophasic' quarter-cycle depolarization. 2. Simulation studies demonstrated that the increased efficacy of the induced quarter-cycle hyperpolarizing-half-cycle depolarizing polyphasic pulse was mainly attributed to the greater duration of the outward membrane current phase, resulting in a greater outward charge transfer afforded by the half-cycle (i.e. quarter-cycles 2 and 3). The advantage of a fast rising initial quarter-cycle depolarization was more than offset by the slower rising, but longer duration depolarizing half-cycle. 3. Simulation further revealed that the quarter-cycle hyperpolarization-half-cycle depolarization showed only a 2.6 % lowering of peak outward current and a 3.5 % lowering of outward charge transfer at threshold, compared with a half-cycle depolarization alone. Presumably, this slight increase in efficacy reflects modest reversal of Na+ inactivation by the very brief initial hyperpolarization. 4. In vitro, at low bath temperature, the nerve response to an initial quarter-cycle depolarization declined in amplitude as the second hyperpolarizing phase progressively increased in amplitude and duration. This 'pull-down' phenomenon nearly disappeared as the bath temperature approached 37 C. Possibly, at the reduced temperature, delay in generation of the action potential permitted the hyperpolarization phase to reduce excitation. 5. Pull-down was not observed in the thenar muscle responses to median nerve stimulation in a normal human at normal temperature. However, pull-down emerged when the median nerve was cooled by placing ice over the forearm. 6. In a nerve at subnormal temperature straddled with non-conducting inhomogeneities, polyphasic pulses of either polarity elicited the largest responses. This was also seen when stimulating distal median nerve at normal temperature. These results imply excitation by hyperpolarizing-depolarizing pulse sequences at two separate sites. Similarly, polyphasic pulses elicited the largest responses from nerve roots and motor cortex. 7. The pull-down phenomenon has a possible clinical application in detecting pathologically slowed activation of Na+ channels. The current direction of the polyphasic waveform may become a significant factor with the increasing use of repetitive magnetic stimulators which, for technical reasons, induce a cosine-shaped half-cycle, preceded and followed by quarter-cycles of opposite polarity.