title: Pathological mechanism of musculoskeletal manifestations associated with CRPS type II: an animal study.
abstract: Patients with complex regional pain syndrome (CRPS) often complain of abnormal sensations beyond the affected body part, but causes of this spread of musculoskeletal manifestations into contiguous areas remain unclear. In addition, immobilization can predispose to the development of CRPS. We examined functional, biochemical, and histological alterations in affected parts, including contiguous zones, using an animal model. Ten-week-old male Wistar rats were assigned to 5 groups: a normal group receiving no treatment, a sham operation group with surgical exploration, an immobilization group with surgical exploration plus internal knee joint immobilization, a surgical neuropathy group prepared by spinal nerve ligation (SNL) of the left L5 nerve root, and a surgical neuropathy+immobilization group with simultaneous SNL and knee joint immobilization. Mechanical allodynia and knee contracture were compared between groups, and tissues were harvested for histological assessments and gene and protein expression analyses. Neither surgical procedures nor immobilization induced detectable mechanical sensitivity. However, the addition of nerve injury resulted in detectable mechanical allodynia, and immobilization not only accelerated hyperalgesia, but also resulted in muscle fibrosis. Nerve growth factor (NGF) and other mediators of neurogenic inflammation were highly expressed not only in denervated muscles, but also in innervated muscles in contiguous areas, suggesting the spread of NGF production beyond the myotome of the injured nerve. Transforming growth factor β was involved in the development of contracture in CRPS. These findings imply that neuroinflammatory components play major roles in the progression and dispersion of both sensory pathologies and pathologies that are exacerbated by immobilization.
authors.affiliation: Department of Hand Surgery, Graduate School of Nagoya University, Nagoya, Japan. Electronic address: hideyuki@circus.ocn.ne.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ota
authors.affiliation: Department of Hand Surgery, Graduate School of Nagoya University, Nagoya, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Arai
authors.affiliation: Department of Hand Surgery, Graduate School of Nagoya University, Nagoya, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Iwatsuki
authors.affiliation: Department of Hand Surgery, Graduate School of Nagoya University, Nagoya, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Urano
authors.affiliation: Department of Hand Surgery, Graduate School of Nagoya University, Nagoya, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kurahashi
authors.affiliation: Department of Hand Surgery, Graduate School of Nagoya University, Nagoya, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kato
authors.affiliation: Department of Hand Surgery, Graduate School of Nagoya University, Nagoya, Japan.
authors.forename: Michiro
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Hand Surgery, Graduate School of Nagoya University, Nagoya, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hirata
mesh_terms: D000818:Animals; D002422:Causalgia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007103:Immobilization; D018836:Inflammation Mediators / Q000378:metabolism; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D020932:Nerve Growth Factor
keywords: Allodynia; Animal experiment; Complex regional pain syndrome; Contracture; Musculoskeletal manifestations; Pain