Anti-interleukin-6 receptor antibody reduces neuropathic pain following spinal cord injury in mice

Murakami,Tomotoshi; Kanchiku,Tsukasa; Suzuki,Hidenori; Imajo,Yasuaki; Yoshida,Yuichiro; Nomura,Hiroshi; Cui,Dan; Ishikawa,Toshizo; Ikeda,Eiji; Taguchi,Toshihiko

doi:10.3892/etm.2013.1296

Anti-interleukin-6 receptor antibody reduces neuropathic pain following spinal cord injury in mice

Authors:
- Tomotoshi Murakami
- Tsukasa Kanchiku
- Hidenori Suzuki
- Yasuaki Imajo
- Yuichiro Yoshida
- Hiroshi Nomura
- Dan Cui
- Toshizo Ishikawa
- Eiji Ikeda
- Toshihiko Taguchi
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Affiliations: Department of Orthopedic Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan, Department of Orthopedic Surgery, Hiroshima Red Cross Hospital, Hiroshima, Hiroshima 730-0052, Japan, Department of Pathology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan, Department of Neurosciences, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan
Published online on: September 13, 2013 https://doi.org/10.3892/etm.2013.1296
Pages: 1194-1198

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Abstract

The present study reports the beneficial effects of an anti-mouse interleukin-6 (IL-6) receptor antibody (MR16-1) on neuropathic pain in mice with spinal cord injury (SCI). Following laminectomy, contusion SCI models were produced using an Infinite Horizon (IH)-impactor. MR16-1 was continuously injected for 14 days using Alzet osmotic pumps. A mouse IL-6 ELISA kit was then used to analyze IL-6 levels in the spinal cord tissue between 12 and 72 h after injury. Motor and sensory functions were evaluated each week using the Basso Mouse Scale (BMS), plantar von Frey and thermal threshold tests. Histological examinations were performed 42 days after SCI. Between 24 and 72 h after SCI, the expression levels of IL-6 were significantly decreased in the MR16-1 treated group. Six weeks after surgery, the BMS score of the MR16-1-treated group indicated significant recovery of neurological functions. MR16-1-treated mice in the SCI group exhibited lower paw withdrawal thresholds in the plantar von Frey and thermal tests, which were used to evaluate allodynia. MR16-1 treatment significantly increased the area of Luxol fast blue‑stained tissue, representing spared myelin sheaths. These results indicate that the continuous inhibition of IL-6 signaling by MR16-1 between the early and sub-acute phases following SCI leads to neurological recovery and the suppression of hyperalgesia and allodynia. Overall, our data suggest that the inhibition of severe inflammation may be a promising neuroprotective approach to limit secondary injury following SCI and that an anti-IL-6 receptor antibody may have clinical potential for the treatment of SCI.

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