據(jù)8月7日的《科學(xué)》雜志報(bào)道說,，被稱作內(nèi)源性大麻醇的化合物近來十分引人注目，因?yàn)樵撐镔|(zhì)可能成為從治療疼痛到肥胖癥的藥物標(biāo)靶,。但該物質(zhì)實(shí)際上能夠放大某些疼痛的信號,，而非像從前所認(rèn)為的可以抑制這類疼痛信號。 這些發(fā)現(xiàn)可能有助于指導(dǎo)人們用能夠調(diào)節(jié)內(nèi)源性大麻醇效應(yīng)的藥物來治療慢性疼痛的各種努力,。 通常,，在慢性疼痛的案例中，神經(jīng)元至神經(jīng)元的傳導(dǎo)會(huì)在脊髓的一個(gè)叫做背角的部分中驟然增加,。
內(nèi)源性大麻醇（相當(dāng)于人體內(nèi)版本的大麻THC）曾經(jīng)被認(rèn)為會(huì)抑制這類的疼痛信號傳導(dǎo),，但Alejandro Pernía-Andrade及其一個(gè)國際團(tuán)隊(duì)的同僚現(xiàn)在顯示，也許相反的情況才是真正發(fā)生的事件,。 他們發(fā)現(xiàn),，在大鼠和小鼠中，疼痛刺激能夠在脊髓中釋放出內(nèi)源性大麻醇，這些內(nèi)源性大麻醇會(huì)作用于一群叫做CB1受體的神經(jīng)元受體,。 這一作用減少了關(guān)鍵性神經(jīng)遞質(zhì)的釋放,，這些神經(jīng)遞質(zhì)是在一個(gè)神經(jīng)元至另外一個(gè)神經(jīng)元之間往返的物質(zhì)，其總體上的效應(yīng)是使神經(jīng)元變得更容易興奮,。 在另外一項(xiàng)在人類自愿者身上所做的試驗(yàn)中,，文章的作者發(fā)現(xiàn)，阻斷CB1受體的藥物Rimonabant可降低在自愿者的皮膚片上所誘導(dǎo)的異常的疼痛的敏感性,。（生物谷Bioon.com）
生物谷推薦原始出處：
Science 7 August 2009:DOI: 10.1126/science.1171870
Spinal Endocannabinoids and CB1 Receptors Mediate C-Fiber–Induced Heterosynaptic Pain Sensitization
Alejandro J. Pernía-Andrade,1,*, Ako Kato,1,9,* Robert Witschi,1,9,* Rita Nyilas,2 István Katona,2 Tamás F. Freund,2 Masahiko Watanabe,3 J?rg Filitz,4 Wolfgang Koppert,4, Jürgen Schüttler,4 Guangchen Ji,5 Volker Neugebauer,5 Giovanni Marsicano,6 Beat Lutz,7 Horacio Vanegas,8 Hanns Ulrich Zeilhofer1,9,
Diminished synaptic inhibition in the spinal dorsal horn is a major contributor to chronic pain. Pathways that reduce synaptic inhibition in inflammatory and neuropathic pain states have been identified, but central hyperalgesia and diminished dorsal horn synaptic inhibition also occur in the absence of inflammation or neuropathy, solely triggered by intense nociceptive (C-fiber) input to the spinal dorsal horn. We found that endocannabinoids, produced upon strong nociceptive stimulation, activated type 1 cannabinoid (CB1) receptors on inhibitory dorsal horn neurons to reduce the synaptic release of -aminobutyric acid and glycine and thus rendered nociceptive neurons excitable by nonpainful stimuli. Our results suggest that spinal endocannabinoids and CB1 receptors on inhibitory dorsal horn interneurons act as mediators of heterosynaptic pain sensitization and play an unexpected role in dorsal horn pain-controlling circuits.
1 Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
2 Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083 Budapest, Hungary.
3 Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.
4 Department of Anesthesiology, University of Erlangen-Nürnberg, Krankenhausstrasse 12, D-91054 Erlangen, Germany.
5 Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555–1069, USA.
6 U862 Centre de Recherche INSERM Fran?ois Magendie, 33077 Bordeaux, France.
7 Institute of Physiological Chemistry and Pathobiochemistry, Johannes Gutenberg-University Mainz, D-55099 Mainz, Germany.
8 Instituto Venezolano de Investigaciones Cientificas, Apartado 20632, Caracas 1020A, Venezuela.
9 Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang Pauli Strasse 10, CH-8093 Zurich, Switzerland.
