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Perineural expression of high‐mobility group box‐1 contributes to long‐lasting mechanical hypersensitivity via matrix metalloprotease‐9 up‐regulation in mice with painful peripheral neuropathy
Author(s) -
Zhang Fang Fang,
Morioka Norimitsu,
Harano Sakura,
Nakamura Yoki,
Liu Keyue,
Nishibori Masahiro,
HisaokaNakashima Kazue,
Nakata Yoshihiro
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13434
Subject(s) - sciatic nerve , hmgb1 , neuropathic pain , medicine , peripheral neuropathy , nociception , peripheral nerve injury , nerve injury , mononeuropathy , anesthesia , endocrinology , inflammation , receptor , diabetes mellitus
High‐mobility group box‐1 (HMGB1) has been shown to be critical in the modulation of nociceptive transduction following a peripheral neuropathy. However, the precise role of peripherally expressed HMGB1 in neuropathic pain has yet to be fully elaborated. Following a partial sciatic nerve ligation (PSNL) in mice, a persistent ipsilateral up‐regulation of HMGB1 was observed from 3 to 21 days after PSNL, in paralleled with a robust ipsilateral hind paw mechanical hypersensitivity. Increased HMGB1 was detected in both infiltrating macrophages and proliferating Schwann cells in the ipsilateral nerve 14 days following PSNL. Repeated perineural treatment with anti‐HMGB1 antibody significantly ameliorated PSNL‐induced mechanical hypersensitivity. Several pronociceptive molecules, including matrix metalloprotease‐9 (MMP‐9), tumor necrosis factor‐α, interleukin‐1β (IL‐1β), and cyclooxygenase‐2, were up‐regulated in injured sciatic nerve 14 days following PSNL. Repeated perineural treatment with an anti‐HMGB1 antibody significantly suppressed expression of MMP‐9, but not other pronociceptive molecules. Perineural treatment with a selective MMP‐9 inhibitor ameliorated PSNL‐induced mechanical hypersensitivity. The current findings demonstrate that the maintenance of the neuropathic state following an injured nerve is dependent on the up‐regulation of HMGB1 and MMP‐9. Thus, blocking HMGB1 function in sciatic nerve could be a potent therapeutic strategy for the treatment of neuropathic pain.Increased peripheral high‐mobility group box‐1 (HMGB1) is involved in the modulation of nociceptive transduction following a peripheral neuropathy. Following nerve injury in mice, increased HMGB1 is detected in both infiltrating macrophages and proliferating Schwann cells in the ipsilateral nerve. Repeated perineural treatment with anti‐HMGB1 antibody significantly ameliorates nerve injury‐induced mechanical hypersensitivity, and suppresses expression of matrix metalloprotease‐9 (MMP‐9). The findings demonstrate that the maintenance of the neuropathic state following an injury nerve is dependent on the up‐regulation of HMGB1 and MMP‐9.