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The Journal of Neuroscience, February 25, 2004, 24(8):1941-1947; doi:10.1523/JNEUROSCI.4975-03.2004

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Development/Plasticity/Repair
Essential Function of Oncostatin M in Nociceptive Neurons of Dorsal Root Ganglia

Yoshihiro Morikawa,^1 * Shinobu Tamura,^1 * Ken-ichi Minehata,² Peter J. Donovan,³ Atsushi Miyajima,^2,4 and Emiko Senba¹

¹Department of Anatomy and Neurobiology, Wakayama Medical University, Wakayama, 641-8509 Japan, ²Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Bioscience, University of Tokyo, Bunkyo-ku, Tokyo, 113-0032 Japan, ³Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, and ⁴Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi 322-0012 Japan

Oncostatin M (OSM) is a member of the interleukin-6 family of cytokines, and we have reported previously that the murine OSM receptor subunit (OSMR) was expressed in some neurons in the adult trigeminal and dorsal root ganglia (DRGs) and in the perineonatal hypoglossal nucleus. In the present study, we investigated the development of OSMR-positive neurons of DRGs in OSM-deficient mice. In situ hybridization revealed that OSMR-positive neurons in DRGs began to appear at postnatal day 0 (P0) and reached the adult level at P14. In the DRGs of the OSM-deficient mice, vanilloid receptor 1 (VR1)- and P2X3-positive small-sized neurons were significantly decreased. In addition, OSMR-positive neurons decreased, resulting in the reduced number of VR1/P2X3/OSMR-triple positive neurons. OSM-deficient mice displayed significantly reduced noxious responses in models of acute thermal, mechanical, chemical, and visceral pain. Thus, OSM plays an essential role in the development of a subtype of nociceptive neurons in the DRGs.

Key words: oncostatin M; receptor; dorsal root ganglion; Ret; VR1; P2X3; mouse; gene-targeting; pain; behavior

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Received Sep 29, 2003; revised December 5, 2003; accepted December 6, 2003.

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