數(shù)十年來,，研究人員一直在設(shè)法尋找瘙癢特異性神經(jīng)細胞,。近日來自約翰霍普金斯大學(xué)的研究人員發(fā)現(xiàn)了一個與瘙癢相關(guān)的傷害感受器細胞亞群，從而為研究瘙癢及開發(fā)止癢治療開辟了新途徑,，相關(guān)論文發(fā)表在12月23日的《自然神經(jīng)科學(xué)》（Nature Neuroscience）雜志上,。
領(lǐng)導(dǎo)這一研究的是約翰霍普金斯醫(yī)學(xué)院的董欣中（Xinzhong Dong）博士，董博士早年畢業(yè)于武漢大學(xué),，后于美國加州大學(xué)洛杉磯分校獲得博士學(xué)位,，現(xiàn)在約翰霍普金斯大學(xué)醫(yī)學(xué)院神經(jīng)科學(xué)系進行研究工作,，主要從事疼痛相關(guān)神經(jīng)細胞的分子與遺傳機制研究。
瘙癢是機體生理狀態(tài)下自我保護的一種反應(yīng)機制,，也是許多系統(tǒng)性疾病和皮膚疾病的癥狀之一,，目前對于其產(chǎn)生的具體機制仍不十分清楚,。一直以來,，許多科學(xué)家對瘙癢是否是疼痛的一種形式或體內(nèi)是否有專門的瘙癢、疼痛及其它感覺的神經(jīng)通路進行過辯論,。并用了數(shù)十年的時間搜尋瘙癢特異性神經(jīng)元細胞,，希望能夠解釋大腦如何把癢和疼痛區(qū)分開來，但卻沒有突破性進展,。
2009年,，董欣中研究小組在上皮感覺神經(jīng)細胞中發(fā)現(xiàn)一個G蛋白偶聯(lián)受體家族成員Mrgprs能行使瘙癢受體中的功能。并證實Mrgprs能夠在小口徑背根神經(jīng)節(jié)（DRG）神經(jīng)細胞中特異性表達,，這種小口徑DGR神經(jīng)細胞能夠感知疼痛和瘙癢,。
在這篇文章中，研究人員證實DGR中的MrgprA3+神經(jīng)元是瘙癢特異性的神經(jīng)細胞,。通過遺傳工程標(biāo)記和操控DRG中的MrgprA3+神經(jīng)元,，研究人員發(fā)現(xiàn)它們對皮膚表皮進行了神經(jīng)支配，并對多種致癢原（pruritogen）產(chǎn)生反應(yīng),。除去MrgprA3+神經(jīng)元可導(dǎo)致多種致癢原誘發(fā)的以及在慢性瘙癢疾病中自發(fā)的搔抓明顯減少,，而疼痛敏感性卻不受影響。值得注意的是,，MrgprA3+神經(jīng)元獨特表達TRPV1的小鼠在對辣椒素做出反應(yīng)時,，顯示出瘙癢而非疼痛行為。盡管MrgprA3+神經(jīng)元對于傷害性熾熱敏感,，然而通過傷害性熾熱激活這些神經(jīng)元中的TRPV1卻不會改變疼痛行為,。
這些結(jié)果表明MrgprA3神經(jīng)元是介導(dǎo)瘙癢的背根神經(jīng)節(jié)神經(jīng)元一種特異的亞型，從而為開發(fā)出新型抗瘙癢治療指明了新研究方向,。(生物谷Bioon.com)
doi:10.1038/nn.3289
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A subpopulation of nociceptors specifically linked to itch
Liang Han,1 Chao Ma,2, 3 Qin Liu,1, 4 Hao-Jui Weng,1, 4 Yiyuan Cui,5 Zongxiang Tang,1, 4 Yushin Kim,1 Hong Nie,3, 6 Lintao Qu,3 Kush N Patel,1, 4 Zhe Li,1 Benjamin McNeil,1 Shaoqiu He,7 Yun Guan,7 Bo Xiao,5 Robert H LaMotte3 & Xinzhong Dong1, 4
Itch-specific neurons have been sought for decades. The existence of such neurons has been doubted recently as a result of the observation that itch-mediating neurons also respond to painful stimuli. We genetically labeled and manipulated MrgprA3+ neurons in the dorsal root ganglion (DRG) and found that they exclusively innervated the epidermis of the skin and responded to multiple pruritogens. Ablation of MrgprA3+ neurons led to substantial reductions in scratching evoked by multiple pruritogens and occurring spontaneously under chronic itch conditions, whereas pain sensitivity remained intact. Notably, mice in which TRPV1 was exclusively expressed in MrgprA3+ neurons exhibited itch, but not pain, behavior in response to capsaicin. Although MrgprA3+ neurons were sensitive to noxious heat, activation of TRPV1 in these neurons by noxious heat did not alter pain behavior. These data suggest that MrgprA3 defines a specific subpopulation of DRG neurons mediating itch. Our study opens new avenues for studying itch and developing anti-pruritic therapies.
