Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados, Unidad Coapa Calzada de los Tenorios 235, Col. Granjas Coapa, Tlalpan, 14330, Ciudad de México, Mexico.
Catedra Conacyt, Estudios Moleculares Avanzados, Instituto de Ecología AC (INECOL). Carretera antigua a Coatepec 351, El Haya, Xalapa, Veracruz, Mexico.
Drug Dev Res. 2017 Dec;78(8):371-380. doi: 10.1002/ddr.21409. Epub 2017 Sep 3.
Preclinical Research Treatment of neuropathic pain is an area of largely unmet medical need. Pregabalin and gabapentin are anticonvulsants widely used for the treatment of neuropathic pain. Unfortunately, these drugs are only effective in 50-60% of the treated patients. In addition, both drugs have substantial side effects. Several studies have reported that ultralow doses of opioid receptor antagonists can induce analgesia and enhance the analgesic effect of opioids in rodents and humans. The objective of the present study was to assess the antiallodynic synergistic interaction between gabapentinoids and naltrexone in rats. Oral administration of pregabalin (ED = 2.79 ± 0.16 mg/kg) or gabapentin (ED = 21.04 ± 2.87 mg/kg) as well as intrathecal naltrexone (ED = 0.11 ± 0.02 ng) reduced in a dose-dependent manner tactile allodynia in rats. Maximal antiallodynic effects (∼100%) were reached with 30 mg/kg of pregabalin, 300 mg/kg of gabapentin or 0.5 ng of naltrexone. Co-administration of pregabalin or gabapentin and naltrexone in a fixed-dose ratio (1:1) remarkably reduced spinal nerve ligation-induced tactile allodynia showing a synergistic interaction. The data indicate that combinations of pregabalin or gabapentin and ultra-low doses of naltrexone are able to reduce tactile allodynia in neuropathic rats with lower doses that those used when drugs are given individually and with an improved side effects profile. Drug Dev Res 78 : 371-380, 2017. © 2017 Wiley Periodicals, Inc.
临床前研究
治疗神经性疼痛是一个很大程度上未满足医疗需求的领域。普瑞巴林和加巴喷丁是广泛用于治疗神经性疼痛的抗惊厥药。不幸的是，这些药物仅在 50-60%的治疗患者中有效。此外，这两种药物都有很大的副作用。一些研究报告称，阿片受体拮抗剂的超低剂量可在啮齿动物和人类中诱导镇痛，并增强阿片类药物的镇痛效果。本研究的目的是评估加巴喷丁类药物和纳曲酮在大鼠中的抗痛觉过敏协同相互作用。普瑞巴林（ED = 2.79 ± 0.16 mg/kg）或加巴喷丁（ED = 21.04 ± 2.87 mg/kg）的口服给药以及鞘内纳曲酮（ED = 0.11 ± 0.02 ng）以剂量依赖性方式减少了大鼠的触觉性痛觉过敏。用 30 mg/kg 的普瑞巴林、300 mg/kg 的加巴喷丁或 0.5 ng 的纳曲酮可达到最大的抗痛觉过敏作用（约 100%）。普瑞巴林或加巴喷丁与纳曲酮以固定剂量比（1:1）联合给药可显著减轻脊髓神经结扎引起的触觉性痛觉过敏，表现出协同相互作用。数据表明，普瑞巴林或加巴喷丁与超低剂量纳曲酮的组合能够降低神经性大鼠的触觉性痛觉过敏，其剂量低于单独使用药物时的剂量，且副作用谱得到改善。药物开发研究 78：371-380，2017。© 2017 威利期刊公司
