Antinociceptive and hypnotic activities of pregabalin in a neuropathic pain-like model in mice

TO evaluate the antinociceptive and hypnotic effects of pregabalin, we established a neuropathic pain-like model in mice using partial sciatic nerve ligation (PSNL), and examined thermal hyperalgesia, mechanical allodynia, electroencephalogram, rota-rod testing, and c-Fos expression in the anterior cingulate cortex. Gabapentin was used as a reference drug in the study. Pregabalin administered i.g. at 12.5 and 25 mg/kg prolonged the duration of thermal latencies by 1.4- and 1.6-fold and increased the mechanical threshold by 2.2- and 3.1-fold 3 h after administration, respectively, but did not affect motor coordination in PSNL mice, compared with vehicle control. Pregabalin (12.5 and 25 mg/kg) given at 6:30 increased the amount of non-rapid eye movement sleep in a 4-h period by 13- and 1.4-fold, respectively, in PSNL mice. However, pregabalin (25 mg/kg) given at 20:30 did not alter the sleep pattern in normal mice. Immunohistochemical study showed that PSNL increased c-Fos expression in the neurons of anterior cingulate cortex by 2.1-fold, which could be reversed by pregabalin. These results indicate that pregabalin is an effective treatment for both neuropathic pain and sleep disturbance in PSNL mice. (C) 2015 Elsevier Inc. All rights reserved.