Pain-like behavior in the collagen antibody-induced arthritis model is regulated by lysophosphatidic acid and activation of satellite glia cells

Jie Su, Emerson Krock, Swapnali Barde, Ada Delaney, Johnny Ribeiro, Jungo Kato, Nilesh Agalave, Gustaf Wigerblad, Rosalia Matteo, Roger Sabbadini, Anna Josephson, Jerold Chun, Kim Kultima, Olivier Peyruchaud, Tomas Hökfelt, Camilla I. Svensson

研究成果: Article査読

1 被引用数 (Scopus)

抄録

Inflammatory and neuropathic-like components underlie rheumatoid arthritis (RA)-associated pain, and lysophosphatidic acid (LPA) is linked to both joint inflammation in RA patients and to neuropathic pain. Thus, we investigated a role for LPA signalling using the collagen antibody-induced arthritis (CAIA) model. Pain-like behavior during the inflammatory phase and the late, neuropathic-like phase of CAIA was reversed by a neutralizing antibody generated against LPA and by an LPA1/3 receptor inhibitor, but joint inflammation was not affected. Autotaxin, an LPA synthesizing enzyme was upregulated in dorsal root ganglia (DRG) neurons during both CAIA phases, but not in joints or spinal cord. Late-phase pronociceptive neurochemical changes in the DRG were blocked in Lpar1 receptor deficient mice and reversed by LPA neutralization. In vitro and in vivo studies indicated that LPA regulates pain-like behavior via the LPA1 receptor on satellite glia cells (SGCs), which is expressed by both human and mouse SGCs in the DRG. Furthermore, CAIA-induced SGC activity is reversed by phospholipid neutralization and blocked in Lpar1 deficient mice. Our findings suggest that the regulation of CAIA-induced pain-like behavior by LPA signalling is a peripheral event, associated with the DRGs and involving increased pronociceptive activity of SGCs, which in turn act on sensory neurons.

本文言語English
ページ(範囲)214-230
ページ数17
ジャーナルBrain, Behavior, and Immunity
101
DOI
出版ステータスPublished - 2022 3月
外部発表はい

ASJC Scopus subject areas

  • 免疫学
  • 内分泌系および自律システム
  • 行動神経科学

フィンガープリント

「Pain-like behavior in the collagen antibody-induced arthritis model is regulated by lysophosphatidic acid and activation of satellite glia cells」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル