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The Journal of Neuroscience, August 12, 2009, 29(32):10000-10009; doi:10.1523/JNEUROSCI.5030-08.2009

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Cellular/Molecular
Membrane-Delimited Coupling of TRPV1 and mGluR5 on Presynaptic Terminals of Nociceptive Neurons

Yong Ho Kim,^1 * Chul-Kyu Park,^1 * Seung Keun Back,² C. Justin Lee,³ Se Jin Hwang,⁴ Yong Chul Bae,⁵ Heung Sik Na,² Joong Soo Kim,¹ Sung Jun Jung,⁶ and Seog Bae Oh¹

¹National Research Laboratory for Pain, Dental Research Institute and Department of Physiology School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea, ²Medical Science Research Center and Department of Physiology, Korea University College of Medicine, Seoul 136-705, Republic of Korea, ³Center for Neural Science Division of Life Science, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea, ⁴Department of Anatomy and Cell Biology, College of Medicine, Hanyang University, Seoul 133-791, Republic of Korea, ⁵Department of Anatomy, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea, and ⁶Department of Physiology, College of Medicine, Kangwon National University, Chunchon 220-710, Republic of Korea

Correspondence should be addressed to either of the following: Dr. Seog Bae Oh, Department of Physiology, School of Dentistry, Seoul National University, 28-2 Yeongeon-Dong Chongno-Ku, Seoul 110-749, Republic of Korea, Email: brainres{at}plaza.snu.ac.kr; or Dr. Sung Jun Jung, Department of Physiology, College of Medicine, Kangwon National University, Chunchon 220-710, Republic of Korea, Email: eurijj{at}naver.com

Transient receptor potential vanilloid subtype 1 (TRPV1) and metabotropic glutamate receptor 5 (mGluR5) located on peripheral sensory terminals have been shown to play critical roles in the transduction and modulation of pain sensation. To date, however, very little is known regarding the significance of functional expression of mGluR5 and TRPV1 on the central terminals of sensory neurons in the dorsal horn of the spinal cord. Here we show that TRPV1 on central presynaptic terminals is coupled to mGluR5 in a membrane-delimited manner, thereby contributing to the modulation of nociceptive synaptic transmission in the substantia gelatinosa neurons of the spinal cord. Further, our results demonstrate that TRPV1 is involved in the pain behaviors induced by spinal mGluR5 activation, and diacylglycerol produced by the activation of mGluR5 mediates functional coupling of mGluR5 and TRPV1 on the presynaptic terminals. Thus, mGluR5–TRPV1 coupling on the central presynaptic terminals of nociceptive neurons may be an important mechanism underlying central sensitization under pathological pain conditions.

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Received Oct. 17, 2008; revised July 1, 2009; accepted July 6, 2009.

Correspondence should be addressed to either of the following: Dr. Seog Bae Oh, Department of Physiology, School of Dentistry, Seoul National University, 28-2 Yeongeon-Dong Chongno-Ku, Seoul 110-749, Republic of Korea, Email: brainres{at}plaza.snu.ac.kr; or Dr. Sung Jun Jung, Department of Physiology, College of Medicine, Kangwon National University, Chunchon 220-710, Republic of Korea, Email: eurijj{at}naver.com

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