Chemokine (C-C motif) receptor 5 Is an important pathological regulator in the development and maintenance of neuropathic pain

Katsuyuki Matsushita, Hidetoshi Tozaki-Saitoh, Chinami Kojima, Takahiro Masuda, Makoto Tsuda, Kazuhide Inoue, Sumio Hoka

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

BACKGROUND:: The 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. METHODS:: A 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. RESULTS:: The 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). CONCLUSIONS:: Pharmacological 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.

Original languageEnglish
Pages (from-to)1491-1503
Number of pages13
JournalAnesthesiology
Volume120
Issue number6
DOIs
Publication statusPublished - Jun 2014

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CCR Receptors
Neuralgia
Hyperalgesia
Chemokine CCL3
Maintenance
Spinal Injections
Spinal Injuries
Spinal Nerves
Microglia
Chemokines
Pharmaceutical Preparations
Reverse Transcription
In Situ Hybridization
Oral Administration
Wistar Rats
Spinal Cord
Immunohistochemistry
Pharmacology
Pain
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

Cite this

Chemokine (C-C motif) receptor 5 Is an important pathological regulator in the development and maintenance of neuropathic pain. / Matsushita, Katsuyuki; Tozaki-Saitoh, Hidetoshi; Kojima, Chinami; Masuda, Takahiro; Tsuda, Makoto; Inoue, Kazuhide; Hoka, Sumio.

In: Anesthesiology, Vol. 120, No. 6, 06.2014, p. 1491-1503.

Research output: Contribution to journalArticle

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