Department of Musculoskeletal Anti-aging Medicine, Sapporo Medical University, Japan; Division of Occupational Therapy, Department of Rehabilitation, Sapporo Tokushu-kai Hospital, Japan.
Department of Musculoskeletal Anti-aging Medicine, Sapporo Medical University, Japan.
J Orthop Sci. 2024 Sep;29(5):1306-1312. doi: 10.1016/j.jos.2023.08.007. Epub 2023 Aug 16.
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.
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.
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.
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.
肢体固定被认为会导致肢体疼痛，包括痛觉过敏。约 50%的慢性肢体疼痛患者抱怨说，他们的异常疼痛在暴露于寒冷后会加重。然而，关于肢体固定与冷敏感之间的关系的研究甚少。本研究旨在探讨肢体固定是否会引起冷敏感，以及踝关节拉伸等体育锻炼是否可以预防其在模型小鼠中的诱导。
我们使用了 44 只 8 周龄雄性 C57Bl/6J 小鼠，其中 32 只为固定组小鼠，12 只为对照组小鼠。通过热塑夹板将小鼠的双侧后肢固定。在固定 1 周后，与对照组小鼠相比，评估固定组小鼠的机械、热和冷敏变化，以及脊髓、背根神经节和受累后足中 TRPV1、TRPA1、TRPM8、IL-1β、IL-6 和 TNFα 的表达水平。此外，我们还研究了踝关节拉伸对固定组小鼠的敏感性和表达水平的影响。
肢体固定组小鼠的机械、热和冷敏均显著增加。此外，在固定期间进行踝关节拉伸可显著预防这些敏化反应的增加。在对照组和固定组（有或无踝关节拉伸）小鼠中，TRPV1、TRPA1 和 TRPM8 的表达水平无显著差异。IL-1 和 IL-6 的表达水平在固定的后肢足部显著增加。此外，踝关节拉伸显著预防了其表达水平的增加。
肢体固定可引起冷敏以及机械和热敏，踝关节拉伸可显著预防模型小鼠的敏化反应诱导。阐明肢体固定患者是否经历冷敏感以及踝关节拉伸是否可能预防敏化反应诱导将具有重要意义。
