• Anesthesiology · Jun 2014

    Chemokine (C-C motif) Receptor 5 Is an Important Pathological Regulator in the Development and Maintenance of Neuropathic Pain.

    • Takahiro Masuda, Hidetoshi Tozaki-Saitoh, Chinami Kojima, and Makoto Tsuda.
    • From the Department of Anesthesiology and Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan (K.M., S.H.); and Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan (H.T.-S., C.K., T.M., M.T., K.I.).
    • Anesthesiology. 2014 Jun 1;120(6):1491-503.

    BackgroundThe chemokine family has been revealed to be involved in the pathogenesis of neuropathic pain. In this study, the authors investigated the role of chemokine (C-C motif) ligand 3 and its receptors chemokine (C-C motif) receptor 1 and chemokine (C-C motif) receptor (CCR) 5 in neuropathic pain.MethodsA spinal nerve injury model was established in adult male Wistar rats. The von Frey test and hot plate test were performed to evaluate neuropathic pain behavior, and real-time quantitative reverse transcription polymerase chain reaction, in situ hybridization, and immunohistochemistry were performed to understand the molecular mechanisms.ResultsThe expression levels of chemokine (C-C motif) ligand 3 and CCR5 messenger RNA in the spinal cord were up-regulated after nerve injury, which was possibly due to CD11b-positive microglia. Single intrathecal administration of recombinant chemokine (C-C motif) ligand 3 produced biphasic tactile allodynia; each phase of pain behavior was induced by different receptors. Intrathecal injection of CCR5 antagonist suppressed the development of tactile allodynia (12.81 ± 1.33 g vs. 3.52 ± 0.41 g [mean ± SEM, drug vs. control in paw-withdrawal threshold]; P < 0.05, n = 6 each) and could reverse established tactile allodynia (10.87 ± 0.91 g vs. 3.43 ± 0.28 g; P < 0.05, n = 8 and 7). Furthermore, Oral administration of CCR5 antagonist could reverse established tactile allodynia (8.20 ± 1.27 g vs. 3.18 ± 0.46 g; P < 0.05, n = 4 each).ConclusionsPharmacological blockade of CCR5 was effective in the treatment of the development and maintenance phases of neuropathic pain. Thus, CCR5 antagonists may be potential new drugs for the treatment of neuropathic pain.

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