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J. Biol. Chem., Vol. 281, Issue 25, 17304-17311, June 23, 2006

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Functional Expression of Thermo-transient Receptor Potential Channels in Dental Primary Afferent Neurons

IMPLICATION FOR TOOTH PAIN^*

Chul-Kyu Park, Mi Sun Kim, Zhi Fang, Hai Ying Li, Sung Jun Jung, Se-Young Choi, Sung Joong Lee, Kyungpyo Park, Joong Soo Kim, and Seog Bae Oh¹

From the Department of Physiology and Molecular and Cellular Neuroscience Program, College of Dentistry and Dental Research Institute, Seoul National University, 28-2 Yeongeon-Dong Chongno-Ku, Seoul 110-749 and the Department of Physiology, College of Medicine, Kangwon National University, Chunchon 200-710, Korea

Temperature signaling can be initiated by members of transient receptor potential family (thermo-TRP) channels. Hot and cold substances applied to teeth usually elicit pain sensation. This study investigated the expression of thermo-TRP channels in dental primary afferent neurons of the rat identified by retrograde labeling with a fluorescent dye in maxillary molars. Single cell reverse transcription-PCR and immunohistochemistry revealed expression of TRPV1, TRPM8, and TRPA1 in subsets of such neurons. Capsaicin (a TRPV1 agonist), menthol (a TRPM8 agonist), and icilin (a TRPM8 and TRPA1 agonist) increased intracellular calcium and evoked cationic currents in subsets of neurons, as did the appropriate temperature changes (>43 °, <25 °, and <17 °C, respectively). Some neurons expressed more than one TRP channel and responded to two or three corresponding stimuli (ligands or thermal stimuli). Immunohistochemistry and single cell reverse transcription-PCR following whole cell recordings provided direct evidence for the association between the responsiveness to thermo-TRP ligands and expression of thermo-TRP channels. The results suggest that activation of thermo-TRP channels expressed by dental afferent neurons contributes to tooth pain evoked by temperature stimuli. Accordingly, blockade of thermo-TRP channels will provide a novel therapeutic intervention for the treatment of tooth pain.

Received for publication, October 12, 2005 , and in revised form, February 15, 2006.

^* This work was supported by the Basic Research Program of the Korea Science & Engineering Foundation (Grant R01-2004-000-10384-0) and by the Brain Research Center of the 21st Century Frontier Research Program (Grant M103KV010009-04K2201-00930) funded by the Ministry of Science and Technology, Republic of Korea. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed. Tel.: 82-2-740-8656; Fax: 82-2-762-5107; E-mail: odolbae{at}snu.ac.kr.

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