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Expression and Co-Expression of VR1, CGRP, and IB4-Binding Glycoprotein in Dorsal Root Ganglion Neurons in Rats: Differences Between the Disc Afferents and the Cutaneous Afferents

Aoki, Yasuchika MD, PhD*†; Ohtori, Seiji MD, PhD*; Takahashi, Kazuhisa MD, PhD*; Ino, Hidetoshi MD, PhD‡; Douya, Hideo MD*; Ozawa, Tomoyuki MD*; Saito, Tomoko MD*; Moriya, Hideshige MD*

doi: 10.1097/01.brs.0000167532.96540.31
Basic Science

Study Design. The expression of vanilloid receptor 1 (VR1), calcitonin gene-related peptide (CGRP), and isolectin B4 (IB4)-binding glycoprotein in dorsal root ganglion (DRG) neurons innervating the lumbar disc and the plantar skin was investigated.

Objective: To characterize the DRG neurons innervating lumbar discs and those innervating cutaneous tissue in rats.

Summary and Background Data. Small nociceptive DRG neurons are divided into nerve growth factor (NGF) sensitive and glial cell line-derived neurotrophic factor (GDNF)-sensitive neurons. CGRP and IB4-binding glycoprotein are recognized as specific markers for NGF and GDNF-sensitive neurons, respectively. VR1 is localized in small DRG neurons.

Methods. Using histochemical staining and retrograde tracing methods, the expression of VR1, CGRP, and IB4-binding glycoprotein in DRG neurons innervating the L5–L6 disc and the plantar skin was examined in rats.

Results. DRG neurons innervating the disc showed positive staining as: 23.4% VR1, 54.4% CGRP, and 1.0% IB4-binding glycoprotein. The following distribution was found for DRG neurons innervating the skin: 35.1% VR1, 41.1% CGRP, and 19.5% IB4-binding glycoprotein. Percentages of neurons positive for VR1 and IB4-binding glycoprotein were significantly lower in DRG neurons innervating the disc than in DRG neurons innervating the skin (P < 0.05), while no significant difference was observed in the percentage of neurons positive for CGRP.

Conclusions. VR1 is less abundant in lumbar disc than in cutaneous tissue. Our data suggest that nociceptive information from the disc is transmitted mostly by NGF-sensitive neurons, while that from the cutaneous tissue is transmitted by both NGF-sensitive and GDNF-sensitive neurons.

It is revealed that the percentages of neurons positive for VR1 and IB4 are significantly lower in dorsal root ganglion neurons innervating the disc than in dorsal root ganglion neurons innervating the skin. These results suggest that VR1 and IB4-positive neurons are less involved in the generation of discogenic pain than cutaneous tissue pain.

From the Departments of Orthopedic Surgery, *Graduate School of Medicine, Chiba University, Chiba, Japan, and †Kamitsuga General Hospital, Tochigi, Japan; and ‡Department of Neurobiology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Acknowledgment date: April 5, 2004. First revision date: July 10, 2004. Second revision date: August 18, 2004. Acceptance date: August 19, 2004.

Supported by a Grant-in-aid (No. 14571358) to Kazuhisa Takahashi for Scientific Research from the Japan Society for the Promotion of Science.

The manuscript submitted does not contain information about medical device(s)/drug(s).

Foundation funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

Address correspondence and reprint requests to Yasuchika Aoki, MD, PhD, Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University. 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan; E-mail: yasuaoki@h6.dion.ne.jp

© 2005 Lippincott Williams & Wilkins, Inc.