{"title":"Static stretching of the ankle prevents cold hypersensitivity associated with limb immobilization in model mice","authors":"","doi":"10.1016/j.jos.2023.08.007","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Limb immobilization is considered to contribute to limb pain including hyperalgesia<span>. Approximately 50% of patients with such chronic limb pain complain that their abnormal pain worsens after exposure to cold. However, there have been few studies on the relationship between limb immobilization and cold hypersensitivity. The aim of this study was to examine whether limb immobilization induces cold hypersensitivity, and whether physical exercise such as ankle stretching prevents its induction in model mice.</span></p></div><div><h3>Method</h3><p><span><span>We used forty-four 8-week-old male C57Bl/6J mice, consisting of 32 immobilized mice and 12 control mice. The bilateral hind limbs of the mice were immobilized by a thermoplastic cast. After limb-immobilization for 1 week, changes in mechanical, thermal and cold hypersensitivity, and the expression levels of </span>TRPV1, TRPA1, </span>TRPM8<span><span>, IL-1β, IL-6, and TNFα in the spinal cord, dorsal root ganglia and the affected </span>hind paw were evaluated in comparison with those in the control mice. In addition, we examined the effect of ankle stretching on the hypersensitivity and expression levels in the limb-immobilized mice.</span></p></div><div><h3>Results</h3><p><span>Mechanical, thermal and cold hypersensitivity were significantly increased in the limb-immobilized mice. In addition, ankle stretching during the immobilization period significantly prevented the increases in those hypersensitivities. There were no significant differences in the expression levels of TRPV1, TRPA1 and </span>TRPM8 among the control, and limb-immobilized mice with and without ankle stretching. The expression levels of IL-1 and IL-6 were significantly increased in the immobilized hind limb paw. Furthermore, ankle stretching significantly prevented the increases in their expression levels.</p></div><div><h3>Conclusion</h3><p>Limb-immobilization induced cold hypersensitivity as well as mechanical and thermal hypersensitivity, and ankle stretching significantly prevented the hypersensitivity induction in the model mice. It would be of great interest to clarify whether a patient with limb-immobilization experiences cold hypersensitivity and whether ankle stretching might prevent hypersensitivity induction in the future.</p></div>","PeriodicalId":16939,"journal":{"name":"Journal of Orthopaedic Science","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Orthopaedic Science","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0949265823002166","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ORTHOPEDICS","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Limb immobilization is considered to contribute to limb pain including hyperalgesia. Approximately 50% of patients with such chronic limb pain complain that their abnormal pain worsens after exposure to cold. However, there have been few studies on the relationship between limb immobilization and cold hypersensitivity. The aim of this study was to examine whether limb immobilization induces cold hypersensitivity, and whether physical exercise such as ankle stretching prevents its induction in model mice.
Method
We used forty-four 8-week-old male C57Bl/6J mice, consisting of 32 immobilized mice and 12 control mice. The bilateral hind limbs of the mice were immobilized by a thermoplastic cast. After limb-immobilization for 1 week, changes in mechanical, thermal and cold hypersensitivity, and the expression levels of TRPV1, TRPA1, TRPM8, IL-1β, IL-6, and TNFα in the spinal cord, dorsal root ganglia and the affected hind paw were evaluated in comparison with those in the control mice. In addition, we examined the effect of ankle stretching on the hypersensitivity and expression levels in the limb-immobilized mice.
Results
Mechanical, thermal and cold hypersensitivity were significantly increased in the limb-immobilized mice. In addition, ankle stretching during the immobilization period significantly prevented the increases in those hypersensitivities. There were no significant differences in the expression levels of TRPV1, TRPA1 and TRPM8 among the control, and limb-immobilized mice with and without ankle stretching. The expression levels of IL-1 and IL-6 were significantly increased in the immobilized hind limb paw. Furthermore, ankle stretching significantly prevented the increases in their expression levels.
Conclusion
Limb-immobilization induced cold hypersensitivity as well as mechanical and thermal hypersensitivity, and ankle stretching significantly prevented the hypersensitivity induction in the model mice. It would be of great interest to clarify whether a patient with limb-immobilization experiences cold hypersensitivity and whether ankle stretching might prevent hypersensitivity induction in the future.
期刊介绍:
The Journal of Orthopaedic Science is the official peer-reviewed journal of the Japanese Orthopaedic Association. The journal publishes the latest researches and topical debates in all fields of clinical and experimental orthopaedics, including musculoskeletal medicine, sports medicine, locomotive syndrome, trauma, paediatrics, oncology and biomaterials, as well as basic researches.