QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.050948v1 306/2/709    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rashid, M. H. Articles by Ueda, H. Search for Related Content PubMed PubMed Citation Articles by Rashid, M. H. Articles by Ueda, H.

NEUROPHARMACOLOGY

Increased Expression of Vanilloid Receptor 1 on Myelinated Primary Afferent Neurons Contributes to the Antihyperalgesic Effect of Capsaicin Cream in Diabetic Neuropathic Pain in Mice

Division of Molecular Pharmacology and Neuroscience, Graduate School of Biomedical Sciences, Nagasaki University Nagasaki, Japan (M.H.R., M.I., H.U.); and Central Research Laboratories, Maruishi Pharmaceutical Co. Ltd., Osaka, Japan (SB)

Topical capsaicin is believed to alleviate pain by desensitizing the vanilloid receptor 1 (VR1) at the peripheral nerve endings. Here, we report that an up-regulation of VR1 expression on myelinated fibers contributes to the antihyperalgesic effect of capsaicin cream in streptozotocin (STZ)-induced diabetic neuropathic pain. Intravenous injection of STZ (200 mg/kg) in mice caused rapid onset of diabetes within 24 h. Thermal and mechanical hyperalgesia developed by 3 days after STZ injection and persisted at all time points tested until 28 days. There was also hyperalgesic response to intraplantar (i.pl.) prostaglandin I₂ (PGI₂) agonist-induced nociception in such mice. Application of capsaicin cream dose dependently reversed the thermal, mechanical, and PGI₂ agonist-induced hyperalgesia observed in the diabetic mice. The i.pl. injection of capsaicin solution (0.4 µg/20 µl) produced nociceptive biting-licking responses in control mice, and these responses were significantly increased in STZ-induced diabetic mice. After neonatal capsaicin-treatment, which destroys most unmyelinated C-fibers, the i.pl. capsaicin-induced biting-licking responses were almost abolished. However, in neonatal capsaicin-treated diabetic mice, the i.pl. capsaicin-induced biting-licking responses reappeared. The i.pl. capsaicin-induced biting-licking responses were blocked by the competitive VR1 antagonist capsazepine. All these results suggest an increase in capsaicin receptor on myelinated fibers due to diabetes. Finally, we confirmed the up-regulation of VR1 expression on myelinated primary afferent neurons of diabetic mice by immunohistochemistry. Together, our results suggest that increased expression of VR1 on myelinated fibers might contribute to the antihyperalgesic effect of topical capsaicin in diabetic neuropathic pain.

Address correspondence to: Dr. Hiroshi Ueda, Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. E-mail: ueda{at}net.nagasaki-u.ac.jp

This article has been cited by other articles:

				H. Xu, W. Tian, Y. Fu, T. T. Oyama, S. Anderson, and D. M. Cohen Functional effects of nonsynonymous polymorphisms in the human TRPV1 gene Am J Physiol Renal Physiol, December 1, 2007; 293(6): F1865 - F1876. [Abstract] [Full Text] [PDF]

				F. Zhang, S. Hong, V. Stone, and P. J. W. Smith Expression of Cannabinoid CB1 Receptors in Models of Diabetic Neuropathy J. Pharmacol. Exp. Ther., November 1, 2007; 323(2): 508 - 515. [Abstract] [Full Text] [PDF]

				M. D. Jhaveri, D. Richardson, D. A. Kendall, D. A. Barrett, and V. Chapman Analgesic Effects of Fatty Acid Amide Hydrolase Inhibition in a Rat Model of Neuropathic Pain J. Neurosci., December 20, 2006; 26(51): 13318 - 13327. [Abstract] [Full Text] [PDF]

				V. Vellani, M. Colucci, R. Lattanzi, E. Giannini, L. Negri, P. Melchiorri, and P. A. McNaughton Sensitization of transient receptor potential vanilloid 1 by the prokineticin receptor agonist Bv8. J. Neurosci., May 10, 2006; 26(19): 5109 - 5116. [Abstract] [Full Text] [PDF]

				S. McGaraughty, K. L. Chu, C. R. Faltynek, and M. F. Jarvis Systemic and Site-Specific Effects of A-425619, a Selective TRPV1 Receptor Antagonist, on Wide Dynamic Range Neurons in CFA-Treated and Uninjured Rats J Neurophysiol, January 1, 2006; 95(1): 18 - 25. [Abstract] [Full Text] [PDF]

				P. Honore, C. T. Wismer, J. Mikusa, C. Z. Zhu, C. Zhong, D. M. Gauvin, A. Gomtsyan, R. El Kouhen, C.-H. Lee, K. Marsh, et al. A-425619 [1-Isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea], a Novel Transient Receptor Potential Type V1 Receptor Antagonist, Relieves Pathophysiological Pain Associated with Inflammation and Tissue Injury in Rats J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 410 - 421. [Abstract] [Full Text] [PDF]

				G. Appendino, L. De Petrocellis, M. Trevisani, A. Minassi, N. Daddario, A. S. Moriello, D. Gazzieri, A. Ligresti, B. Campi, G. Fontana, et al. Development of the First Ultra-Potent "Capsaicinoid" Agonist at Transient Receptor Potential Vanilloid Type 1 (TRPV1) Channels and Its Therapeutic Potential J. Pharmacol. Exp. Ther., February 1, 2005; 312(2): 561 - 570. [Abstract] [Full Text] [PDF]

				S. Hong and J. W. Wiley Early Painful Diabetic Neuropathy Is Associated with Differential Changes in the Expression and Function of Vanilloid Receptor 1 J. Biol. Chem., January 7, 2005; 280(1): 618 - 627. [Abstract] [Full Text] [PDF]