title: Metallothionein deficiency in the injured peripheral nerves of complex regional pain syndrome as revealed by proteomics.
abstract: Complex regional pain syndrome (CRPS) is characterized by persistent and severe pain after trauma or surgery; however, its molecular mechanisms in the peripheral nervous system are poorly understood. Using proteomics, we investigated whether injured peripheral nerves of CRPS patients have altered protein profiles compared with control nerves. We obtained nerve samples from 3 patients with CRPS-2 who underwent resection of part of an injured peripheral nerve. Sural nerves from fresh cadavers with no history of trauma or neuropathic pain served as controls. Proteomic analysis showed that the number and functional distribution of proteins expressed in CRPS and control nerves was similar. Interestingly, metallothionein was absent in the injured nerves of CRPS-2, although it was readily detected in control nerves. Western blotting further confirmed the absence of metallothionein in CRPS-2 nerves, and immunohistochemistry corroborated the deficiency of metallothionein expression in injured nerves from 5 of 5 CRPS patients and 2 of 2 patients with painful neuromas. In contrast, all control nerves, including 5 sural nerves from fresh cadavers and 41 nerves obtained from surgically resected tumors, expressed MT. Furthermore, expression of S100 as a marker for Schwann cells, and neurofilament M as a marker of axons was comparable in both CRPS-2 and controls. Metallothioneins are zinc-binding proteins that are probably involved in protection against injury and subsequent regeneration after CNS damage. Their absence from the injured peripheral nerves of patients with CRPS-2 suggests a potential pathogenic role in generating pain in the damaged peripheral nerves.
authors.affiliation: Department of Biomedical Engineering, Sapporo Medical University School of Medicine, Sapporo, Japan Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan Department of Educational Development, Sapporo Medical University Center for Medical Education, Sapporo, Japan Department of Anatomy, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Gosuke
authors.initials: G
authors.lastname: Oki
authors.forename: Takuro
authors.initials: T
authors.lastname: Wada
authors.forename: Kosuke
authors.initials: K
authors.lastname: Iba
authors.forename: Hikono
authors.initials: H
authors.lastname: Aiki
authors.forename: Kouichi
authors.initials: K
authors.lastname: Sasaki
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Imai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sohma
authors.forename: Kayo
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Mami
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Mineko
authors.initials: M
authors.lastname: Fujimiya
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yamashita
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kokai
mesh_terms: D000328:Adult; D000368:Aged; D002422:Causalgia / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008668:Metallothionein / Q000172:deficiency*; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000378:metabolism; D059348:Peripheral Nerve Injuries / Q000209:etiology* / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D009418:S100 Proteins / Q000378:metabolism; D013497:Sural Nerve / Q000378:metabolism / Q000473:pathology*
chemical_list: D016900:Neurofilament Proteins; D009418:S100 Proteins; C051774:neurofilament protein H; D008668:Metallothionein