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Life Sci. 2013 Mar 12;92(4-5):259-65. doi: 10.1016/j.lfs.2012.12.009. Epub 2013 Jan 16.

Combined antiallodynic effect of Neurotropin® and pregabalin in rats with L5-spinal nerve ligation.

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  • 1Department of Pharmacological Research, Institute of Bio-active Science, Nippon Zoki Pharmaceutical Co., Ltd., 442-1, Kinashi, Kato, Hyogo, 673-1461 Japan.



In this study, we investigated the combined effect of Neurotropin® and pregabalin for L5-spinal nerve ligation (L5-SNL) model in rats and thiopental-induced sleep in mice.


The left fifth lumbar nerve of rats was tightly ligated with silk sutures under pentobarbital anesthesia. The hindpaw withdrawal threshold was measured by application of von Frey filaments. Thiopental sodium was intravenously administered in mice and sleeping time was measured. In L5-SNL rats, an isobolographic analysis was performed to clarify the combined antiallodynic effect of Neurotropin and pregabalin 14 days after ligation in rats. In isobolographic analysis and thiopental-induced sleep test, Neurotropin and pregabalin were orally administered to coincide with the timing of the peak effect of each drug.


Neurotropin (50-200 NU/kg) and pregabalin (2.5-10mg/kg) showed a dose-dependent antiallodynic action in L5-SNL rats. The antiallodynic effect of pregabalin was reversed by intrathecal injection of yohimbine or ondansetron. Isobolographic analysis suggested that the combined antiallodynic effect of Neurotropin and pregabalin in L5-SNL rats may have been more than a mere additive effect. Neurotropin (50-400 NU/kg) had no effect on thiopental-induced sleeping time whereas pregabalin (30-100mg/kg) significantly prolonged it. When the dose of pregabalin was 30 mg/kg, Neurotropin (50-400 NU/kg) did not further exacerbate the prolongation effect of pregabalin on thiopental-induced sleep.


It was suggested that when Neurotropin was administered in combination with pregabalin, it might provide more effective pain relief than that obtained with each agent alone in neuropathic pain without aggravating adverse effects of pregabalin.

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