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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 26, 2005, 25(43):10000-10009; doi:10.1523/JNEUROSCI.2507-05.2005

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science 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 Web of Science (15) Citing Articles via Google Scholar Google Scholar Articles by Narita, M. Articles by Suzuki, T. Search for Related Content PubMed PubMed Citation Articles by Narita, M. Articles by Suzuki, T.

 Previous Article  |  Next Article 

Cellular/Molecular
Protease-Activated Receptor-1 and Platelet-Derived Growth Factor in Spinal Cord Neurons Are Implicated in Neuropathic Pain after Nerve Injury

Minoru Narita, Aiko Usui, Michiko Narita, Keiichi Niikura, Hiroyuki Nozaki, Junaidi Khotib, Yasuyuki Nagumo, Yoshinori Yajima, and Tsutomu Suzuki

Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Recently, it has been reported that both thrombin-sensitive protease-activated receptor 1 (PAR-1) and platelet-derived growth factor (PDGF) are present not only in platelets, but also in the CNS, which indicates that they have various physiological functions. In this study, we evaluated whether PAR-1/PDGF in the spinal cord could contribute to the development of a neuropathic pain-like state in mice. Thermal hyperalgesia and tactile allodynia induced by sciatic nerve ligation were significantly suppressed by repeated intrathecal injection of hirudin, which is characterized as a specific and potent thrombin inhibitor. Furthermore, a single intrathecal injection of thrombin produced long-lasting hyperalgesia and allodynia, and these effects were also inhibited by hirudin in normal mice. In nerveligated mice, the increase in the binding of [³⁵S]GTPS to membranes of the spinal cord induced by thrombin and PAR-1-like immunoreactivity (IR) in the spinal cord were each greater than those in sham-operated mice. Thermal hyperalgesia and tactile allodynia induced by sciatic nerve ligation were also suppressed by repeated intrathecal injection of either the PDGF receptor (PDGFR)/Fc chimera protein or the PDGFR-dependent tyrosine kinase inhibitor AG17 [(3,5-di-tert-butyl-4-hydroxybenzylidene)-malononitrile]. Moreover, thermal hyperalgesia and tactile allodynia induced by thrombin in normal mice were virtually eliminated by intrathecal pretreatment with PDGFR/Fc. In immunohistochemical studies, PAR-1-like IR-positive cells in the spinal dorsal horn were mostly colocated on PDGF-like IR-positive neuronal cells. These data provide novel evidence that PAR-1 and PDGF-A-mediated signaling pathway within spinal cord neurons may be directly implicated in neuropathic pain after nerve injury in mice.

Key words: thrombin; protease-activated receptor-1; platelet-derived growth factor; neuropathic pain; spinal cord; pain

---

Received Feb 23, 2005; revised September 2, 2005; accepted September 9, 2005.

This article has been cited by other articles:

				T. Fujita, T. Liu, T. Nakatsuka, and E. Kumamoto Proteinase-Activated Receptor-1 Activation Presynaptically Enhances Spontaneous Glutamatergic Excitatory Transmission in Adult Rat Substantia Gelatinosa Neurons J Neurophysiol, July 1, 2009; 102(1): 312 - 319. [Abstract] [Full Text] [PDF]

				J. Andrae, R. Gallini, and C. Betsholtz Role of platelet-derived growth factors in physiology and medicine Genes & Dev., May 15, 2008; 22(10): 1276 - 1312. [Abstract] [Full Text] [PDF]

				E. Shavit, O. Beilin, A. D. Korczyn, C. Sylantiev, R. Aronovich, V. E. Drory, D. Gurwitz, I. Horresh, R. Bar-Shavit, E. Peles, et al. Thrombin receptor PAR-1 on myelin at the node of Ranvier: a new anatomy and physiology of conduction block Brain, April 1, 2008; 131(4): 1113 - 1122. [Abstract] [Full Text] [PDF]

				J.-i. Ito, Y. Nagayasu, K. Okumura-Noji, R. Lu, T. Nishida, Y. Miura, K. Asai, A. Kheirollah, S. Nakaya, and S. Yokoyama Mechanism for FGF-1 to regulate biogenesis of apoE-HDL in astrocytes J. Lipid Res., September 1, 2007; 48(9): 2020 - 2027. [Abstract] [Full Text] [PDF]

				T. Nagai, M. Ito, N. Nakamichi, H. Mizoguchi, H. Kamei, A. Fukakusa, T. Nabeshima, K. Takuma, and K. Yamada The Rewards of Nicotine: Regulation by Tissue Plasminogen Activator-Plasmin System through Protease Activated Receptor-1. J. Neurosci., November 22, 2006; 26(47): 12374 - 12383. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help