据8月7日的《科学》杂志报道说，被称作内源性大麻醇的化合物近来十分引人注目，因为该物质可能成为从治疗疼痛到肥胖症的药物标靶。但该物质实际上能够放大某些疼痛的信号，而非像从前所认为的可以抑制这类疼痛信号。 这些发现可能有助于指导人们用能够调节内源性大麻醇效应的药物来治疗慢性疼痛的各种努力。 通常，在慢性疼痛的案例中，神经元至神经元的传导会在脊髓的一个叫做背角的部分中骤然增加。

　　内源性大麻醇（相当于人体内版本的大麻THC）曾经被认为会抑制这类的疼痛信号传导，但Alejandro Pernía-Andrade及其一个国际团队的同僚现在显示，也许相反的情况才是真正发生的事件。 他们发现，在大鼠和小鼠中，疼痛刺激能够在脊髓中释放出内源性大麻醇，这些内源性大麻醇会作用于一群叫做CB1受体的神经元受体。 这一作用减少了关键性神经递质的释放，这些神经递质是在一个神经元至另外一个神经元之间往返的物质，其总体上的效应是使神经元变得更容易兴奋。 在另外一项在人类自愿者身上所做的试验中，文章的作者发现，阻断CB1受体的药物Rimonabant可降低在自愿者的皮肤片上所诱导的异常的疼痛的敏感性。

　　推荐原始出处：

　　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.