Sarret Philippe, Doré-Savard Louis, Beaudet Nicolas
Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
Methods Mol Biol. 2010;623:383-95. doi: 10.1007/978-1-60761-588-0_25.
Pain is the new burden of the twenty-first century, raising enormous socio-economic costs to developed and underdeveloped countries. Chronic pain is a central nervous system (CNS) pathology, affecting a large proportion of the population. Morphine and its derivatives are still the golden clinical standards for treating pain although they induce severe side effects. To this day, we still have poor understanding of nociceptive pain and its underlying complex mechanisms; furthermore, novelty in clinical analgesics is lacking.RNA interference technologies are promising both for pain research and treatment. This genetic approach will likely provide new insights into pain mechanisms and eventually offer nonpharmacological therapeutic approaches. In vivo research is thus crucial to reach this goal. Preclinical studies on rodents are necessary to validate small interfering RNA (siRNA) candidates and to target precise physiological pain modulators. Aiming treatment at the CNS is delicate work, and here we will describe how to perform adequate pain research using siRNA, including siRNA preparation and injection, animal behavioral models, and CNS tissue collection.
疼痛是21世纪的新负担,给发达国家和不发达国家带来了巨大的社会经济成本。慢性疼痛是一种中枢神经系统(CNS)病理学疾病,影响着很大一部分人口。吗啡及其衍生物仍然是治疗疼痛的黄金临床标准,尽管它们会引发严重的副作用。时至今日,我们对伤害性疼痛及其潜在的复杂机制仍知之甚少;此外,临床镇痛药缺乏创新性。RNA干扰技术在疼痛研究和治疗方面都很有前景。这种基因方法可能会为疼痛机制提供新的见解,并最终提供非药物治疗方法。因此,体内研究对于实现这一目标至关重要。对啮齿动物进行临床前研究对于验证小干扰RNA(siRNA)候选物和靶向精确的生理性疼痛调节因子是必要的。针对中枢神经系统进行治疗是一项精细的工作,在此我们将描述如何使用siRNA进行充分的疼痛研究,包括siRNA的制备和注射、动物行为模型以及中枢神经系统组织采集。