title: Induction of high mobility group box-1 in dorsal root ganglion contributes to pain hypersensitivity after peripheral nerve injury.
abstract: Pro-inflammatory cytokine high mobility group box-1 (HMGB-1) is involved in inflammation in the central nervous system, but less is known about its biological effects in the peripheral nervous system. In the present study, the role of HMGB-1 in the primary afferent nerve was investigated in the context of the pathophysiology of peripheral nerve injury-induced pain hypersensitivity. Real-time PCR confirmed an increase in HMGB-1 mRNA expression in the dorsal root ganglion (DRG) and spinal nerve at 1 day after spinal nerve ligation (SNL). Induction of HMGB-1 mRNA was observed in both injured L5 and uninjured L4. Immunohistochemistry for HMGB-1 revealed that SNL-induced HMGB-1 expression in the primary afferent neurons and satellite glial cells (SGCs) in the DRG, and in Schwann cells in the spinal nerve. Up-regulation of HMGB-1 was associated with translocation of its signal from the nucleus to the cytoplasm. Injection of HMGB-1 into the sciatic nerve produces transient behavioural hyperalgesia. Neutralizing antibody against HMGB-1 successfully alleviated the mechanical allodynia observed after SNL treatment. Receptor for advanced glycation end products (RAGE), one of the major receptors for HMGB-1, was expressed in the primary afferent neurons and SGCs in the DRG, as well as in Schwann cells in the spinal nerve. These results indicate that HMGB-1 is synthesized and secreted into the DRG and spinal nerve, and contributes to the development of neuropathic pain after nerve injury. Blocking HMGB-1/RAGE signalling might thus be a promising therapeutic strategy for the management of neuropathic pain.
authors.affiliation: Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shibasaki
authors.forename: Mika
authors.initials: M
authors.lastname: Sasaki
authors.forename: Mayumi
authors.initials: M
authors.lastname: Miura
authors.forename: Keiko
authors.initials: K
authors.lastname: Mizukoshi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueno
authors.forename: Satoru
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Fumimasa
authors.initials: F
authors.lastname: Amaya
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000502:physiology; D024243:HMGB1 Protein / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D010523:Peripheral Nervous System Diseases / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D024243:HMGB1 Protein; C104200:Hbp1 protein, rat
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