Perineural Treatment with High Mobility Group Box-1 Monoclonal Antibody Prevents Initiation of Pain-Like Behaviors in Female Mice with Trigeminal Neuropathy

Simeng Ma; Yoki Nakamura; Takahiro Kochi; Suzuna Uemoto; Kazue Hisaoka-Nakashima; Dengli Wang; Keyue Liu; Hidenori Wake; Masahiro Nishibori; Norimitsu Morioka

doi:10.1248/bpb.b23-00729

Regular Article

Perineural Treatment with High Mobility Group Box-1 Monoclonal Antibody Prevents Initiation of Pain-Like Behaviors in Female Mice with Trigeminal Neuropathy

Simeng Ma, Yoki Nakamura , Takahiro Kochi, Suzuna Uemoto, Kazue Hisaoka-Nakashima, Dengli Wang, Keyue Liu, Hidenori Wake, Masahiro Nishibori, Norimitsu Morioka

Author information

Simeng Ma
Department of Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University
Yoki Nakamura Corresponding author
Department of Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University
Takahiro Kochi
Department of Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University
Department of Dental Anesthesiology, Graduate School of Biomedical and Health Sciences, Hiroshima University
Suzuna Uemoto
Department of Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University
Kazue Hisaoka-Nakashima
Department of Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University
Dengli Wang
Department of Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Keyue Liu
Department of Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Hidenori Wake
Department of Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Department of Pharmacology, Faculty of Medicine, Kindai University
Masahiro Nishibori
Department of Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Department of Translational Research & Dug Development, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Norimitsu Morioka Corresponding author
Department of Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University

Keywords: female mouse, high mobility group box 1, macrophage, microglia, neutralizing antibody, trigeminal neuropathy

JOURNAL FREE ACCESS FULL-TEXT HTML

2024 Volume 47 Issue 1 Pages 221-226

DOI https://doi.org/10.1248/bpb.b23-00729

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Abstract

Post-traumatic trigeminal neuropathy (PTTN) is a type of chronic pain caused by damage to the trigeminal nerve. A previous study reported that pretreatment with anti-high mobility group box-1 (HMGB1) neutralizing antibodies (nAb) prevented the onset of PTTN following distal infraorbital nerve chronic constriction injury (dIoN-CCI) in male mice. Clinical evidence indicates a high incidence of PTTN in females. Although our previous study found that perineural HMGB1 is crucial in initiation of PTTN in male mice, it is currently unknown whether HMGB1 is also involved in the pathogenesis of PTTN in female mice. Therefore, in the current study, we examined the effect of anti-HMGB1 nAb on pain-like behavior in female mice following dIoN-CCI surgery. We found that dIoN-CCI surgery enhanced reactivity to mechanical and cold stimuli in female mice, which was suppressed by treatment with anti-HMGB1 nAb. Moreover, the increase in macrophages after dIoN-CCI was significantly attenuated by pretreatment with anti-HMGB1 nAb. Furthermore, anti-HMGB1 nAb treatment inhibited microglial activation in the trigeminal spinal tract nucleus. These data suggest that HMGB1 also plays a crucial role in the onset of PTTN after nerve injury in female mice. Thus, anti-HMGB1 nAb could be a novel therapeutic agent for inhibiting the onset of PTTN in female and male mice.

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