Department of Basic Sciences, New York Institute of Technology College of Osteopathic Medicine, Arkansas State University, Jonesboro, AR, United States.
Department of Pharmacology, College of Medicine, University of Arizona Health Sciences Center, Tucson, AZ, United States.
Pain. 2019 Aug;160(8):1847-1855. doi: 10.1097/j.pain.0000000000001569.
Data from preclinical research have been suggested to suffer from a lack of inherent reproducibility across laboratories. The goal of our study was to replicate findings from a previous report that demonstrated positive effects of Meteorin, a novel neurotrophic factor, in a rat model of neuropathic pain induced by chronic constriction injury (CCI). Notably, 5 to 6 intermittent subcutaneous (s.c.) injections of Meteorin had been reported to produce reversal of mechanical allodynia/thermal hyperalgesia after injury, wherein maximum efficacy of Meteorin was reached slowly and outlasted the elimination of the compound from the blood by several weeks. Here, we evaluated the efficacy of Meteorin in reversing hindpaw mechanical hyperalgesia and cold allodynia in male, Sprague-Dawley rats with CCI. Nociceptive behavior was monitored before and after CCI, and after drug treatment until day 42 after injury. Systemic administration of recombinant mouse Meteorin (0.5 and 1.8 mg/kg, s.c.) at days 10, 12, 14, 17, and 19 after CCI produced a prolonged reversal of neuropathic hypersensitivity with efficacy comparable with that obtained with gabapentin (100 mg/kg, orally). Despite some protocol deviations (eg, nociceptive endpoint, animal vendor, testing laboratory, investigator, etc.) being incurred, these did not affect study outcome. By paying careful attention to key facets of study design, using bioactive material, and confirming drug exposure, the current data have replicated the salient findings of the previous study, promoting confidence in further advancement of this novel molecule as a potential therapy for neuropathic pain.
来自临床前研究的数据表明,实验室之间存在固有可重复性差的问题。我们的研究目的是复制先前研究的结果,该研究表明 Meteorin(一种新型神经营养因子)对慢性缩窄性损伤(CCI)诱导的神经病理性疼痛大鼠模型具有积极作用。值得注意的是,先前的研究报告称,5 至 6 次间歇性皮下(s.c.)注射 Meteorin 可逆转损伤后的机械性痛觉过敏/热痛觉过敏,其中 Meteorin 的最大疗效缓慢达到,并持续数周超过化合物从血液中消除的时间。在这里,我们评估了 Meteorin 在逆转 CCI 雄性 Sprague-Dawley 大鼠后爪机械性痛觉过敏和冷触痛中的疗效。在 CCI 前后以及药物治疗后至损伤后 42 天监测伤害性行为。CCI 后第 10、12、14、17 和 19 天,系统给予重组小鼠 Meteorin(0.5 和 1.8 mg/kg,s.c.)可延长神经病理性敏感性的逆转,疗效与加巴喷丁(100 mg/kg,口服)相当。尽管存在一些方案偏差(例如,伤害性终点、动物供应商、测试实验室、研究者等),但这些偏差并未影响研究结果。通过仔细注意研究设计的关键方面、使用生物活性物质以及确认药物暴露,当前数据复制了先前研究的显著发现,进一步增强了将该新型分子作为治疗神经病理性疼痛的潜在疗法的信心。