Anti-high-mobility group box 1 Neutralizing Antibody Ameliorates Pain Hypersensitivity Induced by Intraplantar Administration of Complete Freund’s Adjuvant in Rats

Abstract

Abstract Mechanisms underlying inflammation-induced pain remain elusive, but research has shown that inflammatory cytokines and immune responses in the spinal cord are especially involved. First reported as a nonhistone chromosomal protein, high-mobility group box 1 (HMGB1) is now implicated as a novel proinflammatory cytokine and crucial mediator of inflammation. We hypothesized that HMGB1 could trigger the release of cytokines in the spinal cord and contribute to inflammatory pain (IP). To test this hypothesis, we first built an IP model induced by intraplantar administration of complete Freund’s adjuvant (CFA) in rats. Moreover, an anti-HMGB1 antibody was injected intrathecally 1, 4, and 14 days after the adjuvant was administered. Pain behavioral responses were measured using a series of tests, and the expressions of spinal HMGB1, interleukin-1 beta (IL-β), and tumor necrosis factor alpha (TNF-α) were assessed. We found that intrathecal injection of the anti-HMGB1 antibody could effectively alleviate the behavioral hypersensitivity and reduce the expressions of spinal HMGB1, IL-β and TNF-α in IP rats. These results suggest that HMGB1 plays an important role in the development of IP induced by intraplantar administration of complete Freund's adjuvant. HMGB1 blocking therapy holds potential in the treatment of IP.