英国伦敦大学学院最新研究发现，Small RNA（sRNA）会调节与慢性炎性痛相关的基因表达水平，这种与已知的疼痛机理完全不同的机制，可能是慢性炎性痛的最大弱点。研究人员称，新发现有助于开发出治疗慢性炎性痛的全新药物。
疼痛有急性疼痛和慢性疼痛之分。与急性疼痛相比，慢性疼痛持续时间长，对人身体和精神上的损害更大。许多慢性疼痛是由如关节炎等炎症引起，称为慢性炎性痛。
伦敦大学学院的约翰伍德教授指出，当一个人经受慢性炎性痛时，其痛阈会急剧降低，看似平常的行为，如走路、穿衣，都可能引起疼痛。慢性炎性痛可通过镇痛药来治疗，但这类药物通常会作用于全身，影响人体对急性痛感的敏锐度，这对于人体保护自身免受伤害十分不利。设想一个人不小心碰到火炉子，却没有锐痛的感觉会怎么样？他不会反射性地移开手臂，结果则会造成严重烧伤。
为检测Small RNA在末梢性疼痛通路中的作用，研究人员删除了实验鼠神经细胞中的Dicer酶（这种酶会影响体内小RNA水平）。他们发现，缺少Dicer酶的实验鼠对急性疼痛有正常的反应，但不会受到通常可引起慢性炎性痛的任何炎症影响。研究人员认为，这是因为Small RNA会调节与慢性炎性痛相关的基因表达水平，而缺少了Dicer酶，实验鼠体内Small RNA水平下降,从而使得许多该类基因不能充分表达，老鼠便不会感觉到炎症引起的痛感。他们得出结论，Small RNA对于钠离子通道表达、疼痛感受器的应激性和痛阈都起着重要的控制、调节作用。
伍德教授表示，要治疗慢性炎性痛，需要恢复慢性炎性痛病人的痛阈，而不损害他们的急性痛感敏锐度，目前使用的阿司匹林类药物是有效的，但有很大的副作用，而新发现为新药的开发提供了一个全新思路，Small RNA将会是一个有效的药物标靶。
该研究发表在最近一期《神经科学杂志》上。
推荐原文出处：
The Journal of Neuroscience doi:10.1523/JNEUROSCI.1980-10.2010
Small RNAs Control Sodium Channel Expression, Nociceptor Excitability, and Pain Thresholds
Jing Zhao,1 * Man-Cheung Lee,1 * Ali Momin,1 Cruz-Miguel Cendan,1,4 Samuel T. Shepherd,1 Mark D. Baker,5 Curtis Asante,2 Lucy Bee,2 Audrey Bethry,1 James R. Perkins,3 Mohammed A. Nassar,1 Bjarke Abrahamsen,1 Anthony Dickenson,2 Bradly S. Cobb,6 Matthias Merkenschlager,7 and John N. Wood1,8
1Molecular Nociception Group, Wolfson Institute for Biomedical Research, 2Research Department of Neuroscience, Physiology and Pharmacology, and 3Institute of Structural and Molecular Biology, University College London, London WC1E 6BT, United Kingdom, 4Department of Pharmacology and Institute of Neuroscience, Faculty of Medicine, University of Granada, 18012 Granada, Spain, 5Neuroscience Centre, Queen Mary's School of Medicine and Dentistry, London E1 2AT, United Kingdom, 6Veterinary Basic Sciences, Royal Veterinary College, London NW1 0TU, United Kingdom, 7Lymphocyte Development Group, Medical Research Council Clinical Sciences Centre, Imperial College London, London W12 0NN, United Kingdom, and 8World Class University Program, Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul 151-742, South Korea
To examine the role of small RNAs in peripheral pain pathways, we deleted the enzyme Dicer in mouse postmitotic damage-sensing neurons. We used a Nav1.8-Cre mouse to target those nociceptors important for inflammatory pain. The conditional null mice were healthy with a normal number of sensory neurons and normal acute pain thresholds. Behavioral studies showed that inflammatory pain was attenuated or abolished. Inflammatory mediators failed to enhance excitability of Nav1.8+ sensory neurons from null mutant mice. Acute noxious input into the dorsal horn of the spinal cord was apparently normal, but the increased input associated with inflammatory pain measured using c-Fos staining was diminished. Microarray and quantitative real-time reverse-transcription PCR (qRT-PCR) analysis showed that Dicer deletion lead to the upregulation of many broadly expressed mRNA transcripts in dorsal root ganglia. By contrast, nociceptor-associated mRNA transcripts (e.g., Nav1.8, P2xr3, and Runx-1) were downregulated, resulting in lower levels of protein and functional expression. qRT-PCR analysis also showed lowered levels of expression of nociceptor-specific pre-mRNA transcripts. MicroRNA microarray and deep sequencing identified known and novel nociceptor microRNAs in mouse Nav1.8+ sensory neurons that may regulate nociceptor gene expression.
