Mechanical pain of the lower extremity after compression of the upper spinal cord involves signal transducer and activator of transcription 3-dependent reactive astrocytes and interleukin-6

Teruaki Ono, Yuta Kohro, Keita Kohno, Hidetoshi Tozaki-Saitoh, Yasuharu Nakashima, Makoto Tsuda

研究成果: ジャーナルへの寄稿学術誌査読

6 被引用数 (Scopus)

抄録

Chronic pain is one of the main symptoms of spinal disorders such as spinal canal stenosis. A major cause of this pain is related to compression of the spinal cord, and chronic pain can develop at the level of the compressed spinal segment. However, in many patients chronic pain arises in an area that does not correspond to the compressed segment, and the underlying mechanism involved remains unknown. This was investigated in the present study using a mouse model of spinal cord compression in which mechanical pain of the hindpaws develops after compression of the first lumbar segment (L1) of the spinal cord. Compression induced the activation of astrocytes in the L1 spinal dorsal horn (SDH)—but not the L4 SDH that corresponds to the hindpaws—and activated signal transducer and activator of transcription 3 (STAT3). Suppressing reactive astrocytes by expressing a dominant negative form of STAT3 (dnSTAT3) in the compressed SDH prevented mechanical pain. Expression of interleukin (IL)-6 was also upregulated in the compressed SDH, and it was inhibited by astrocytic expression of dnSTAT3. Intrathecal administration of a neutralizing anti-IL-6 antibody reversed the compression-induced mechanical pain. These results suggest that astrocytic STAT3 and IL-6 in the compressed SDH are involved in remote mechanical pain observed in the lower extremity, and may provide a target for treating chronic pain associated with spinal cord compression such as spinal canal stenosis.

本文言語英語
ページ(範囲)389-399
ページ数11
ジャーナルBrain, Behavior, and Immunity
89
DOI
出版ステータス出版済み - 10月 2020

!!!All Science Journal Classification (ASJC) codes

  • 免疫学
  • 内分泌系および自律システム
  • 行動神経科学

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