英國倫敦大學(xué)學(xué)院最新研究發(fā)現(xiàn),，Small RNA（sRNA）會調(diào)節(jié)與慢性炎性痛相關(guān)的基因表達(dá)水平，這種與已知的疼痛機(jī)理完全不同的機(jī)制,，可能是慢性炎性痛的最大弱點(diǎn),。研究人員稱，新發(fā)現(xiàn)有助于開發(fā)出治療慢性炎性痛的全新藥物,。
疼痛有急性疼痛和慢性疼痛之分,。與急性疼痛相比，慢性疼痛持續(xù)時(shí)間長，對人身體和精神上的損害更大,。許多慢性疼痛是由如關(guān)節(jié)炎等炎癥引起,，稱為慢性炎性痛。
倫敦大學(xué)學(xué)院的約翰·伍德教授指出,，當(dāng)一個(gè)人經(jīng)受慢性炎性痛時(shí),，其痛閾會急劇降低，看似平常的行為,，如走路,、穿衣，都可能引起疼痛,。慢性炎性痛可通過鎮(zhèn)痛藥來治療,，但這類藥物通常會作用于全身，影響人體對急性痛感的敏銳度,，這對于人體保護(hù)自身免受傷害十分不利,。設(shè)想一個(gè)人不小心碰到火爐子，卻沒有銳痛的感覺會怎么樣,？他不會反射性地移開手臂,，結(jié)果則會造成嚴(yán)重?zé)齻?/p>
為檢測Small RNA在末梢性疼痛通路中的作用，研究人員刪除了實(shí)驗(yàn)鼠神經(jīng)細(xì)胞中的Dicer酶（這種酶會影響體內(nèi)小RNA水平）,。他們發(fā)現(xiàn),，缺少Dicer酶的實(shí)驗(yàn)鼠對急性疼痛有正常的反應(yīng)，但不會受到通?？梢鹇匝仔酝吹娜魏窝装Y影響,。研究人員認(rèn)為，這是因?yàn)镾mall RNA會調(diào)節(jié)與慢性炎性痛相關(guān)的基因表達(dá)水平,，而缺少了Dicer酶,，實(shí)驗(yàn)鼠體內(nèi)Small RNA水平下降,從而使得許多該類基因不能充分表達(dá)，老鼠便不會感覺到炎癥引起的痛感,。他們得出結(jié)論,，Small RNA對于鈉離子通道表達(dá)、疼痛感受器的應(yīng)激性和痛閾都起著重要的控制,、調(diào)節(jié)作用,。
伍德教授表示，要治療慢性炎性痛,，需要恢復(fù)慢性炎性痛病人的痛閾,，而不損害他們的急性痛感敏銳度，目前使用的阿司匹林類藥物是有效的,，但有很大的副作用,，而新發(fā)現(xiàn)為新藥的開發(fā)提供了一個(gè)全新思路,，Small RNA將會是一個(gè)有效的藥物標(biāo)靶。
該研究發(fā)表在最近一期《神經(jīng)科學(xué)雜志》上,。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
