Yuzuncu Yil University Medical Faculty, Physical Medicine and Rehabilitation Department, 65100 Van, Turkey.
Med Hypotheses. 2010 Sep;75(3):319-23. doi: 10.1016/j.mehy.2010.03.012. Epub 2010 Apr 7.
Complex regional pain syndrome (CRPS) is the complication of some injuries, such as a fracture, which affects the distal end of the injured extremity characterized by pain, allodynia, hyperalgesia, edema, abnormal vasomotor and sudomotor activity, movement disorders, joint stiffness, regional osteoporosis, and dystrophic changes in soft tissue. Exact pathogenic mechanism of CRPS is still unclear. Suggested pathogenic mechanisms of CRPS are evaluated in four major groups consist of classic inflammation, hypoxic changes and chronic ischemia, neurogenic inflammation and sympathetic dysregulation. All of these suggested pathogenic mechanisms produced by inflammatory cytokines mediated by nuclear factor kappaB. Vitamin K is a family of structurally similar, fat-soluble, 2-methyl-1,4-naphthoquinones. Vitamin K exerts a powerful influence on bone formation, especially in osteoporosis. Fat in bone stores some vitamin K. Gamma-carboxylation of the glutamic acid in osteocalcin is vitamin K dependent. Osteocalcin plays a role in calcium uptake and bone mineralization. Osteocalcin, the most abundant non-collagenous protein in bone, is produced by osteoblasts during bone matrix formation. Because osteocalcin is not carboxylated in case of vitamin K deficiency at the distal site of fracture or injury, it cannot bind to hydroxyapatite causing osteoporosis. Fracture starts a local inflammatory process in the fracture site and adjacent tissues as seen in CRPS. Vitamin K was shown to suppress the inflammatory cytokines and NF-kappaB and prevent oxidative, hypoxic, ischemic injury (which have key role in both initiation and progression of CRPS) to oligodendrocytes and neurons. We hypothesized that vitamin K has a key role and modulatory effect in CRPS pathogenesis. Vitamin K deficiency at the distal site of fracture occurs because of diminished and slowed circulation, local immobilization after extremity fracture or injury and use of vitamin K store at the distal site of the injured extremity and in the circulation for fracture healing and bone remodelling. In case of vitamin K deficiency at the distal site of fracture, classic inflammation starts with fracture at the distal tissues could not be restricted and classic inflammation, hypoxic changes, chronic ischemia, neurogenic inflammation, sympathetic dysregulation, which are the pathogenic mechanisms of CRPS, and patchy osteoporosis which occur due to high level of under-carboxylated osteocalcin could not be prevented. Briefly vitamin K level decreases in the distal site of the injured extremity consequently resulting in patchy osteoporosis due to high level of under-carboxylated osteocalcin and unrestricted inflammation which are the cause for both initiation and progression of CRPS.
复杂性区域疼痛综合征（CRPS）是某些损伤的并发症，例如骨折，它会影响受伤肢体的末端，其特征是疼痛、感觉过敏、痛觉过敏、水肿、血管运动和汗腺活动异常、运动障碍、关节僵硬、局部骨质疏松症和软组织营养不良性改变。CRPS 的确切发病机制尚不清楚。CRPS 的发病机制被评估为四个主要组，包括经典炎症、缺氧变化和慢性缺血、神经源性炎症和交感神经调节。所有这些被认为的发病机制都是由核因子 kappaB 介导的炎症细胞因子产生的。维生素 K 是一组结构相似、脂溶性、2-甲基-1,4-萘醌。维生素 K 对骨形成有强大的影响，特别是在骨质疏松症中。骨中的脂肪储存一些维生素 K。骨钙素中谷氨酸的 γ-羧化作用依赖于维生素 K。骨钙素在钙摄取和骨矿化中发挥作用。骨钙素是骨中最丰富的非胶原蛋白，由成骨细胞在骨基质形成过程中产生。由于在骨折或损伤的远端部位缺乏维生素 K，骨钙素不能羧化，不能与羟磷灰石结合，导致骨质疏松症。骨折在骨折部位和相邻组织中引发局部炎症过程，如 CRPS 所见。维生素 K 已被证明可抑制炎症细胞因子和 NF-kappaB，并防止氧化、缺氧、缺血损伤（在 CRPS 的启动和进展中起关键作用）对少突胶质细胞和神经元的损伤。我们假设维生素 K 在 CRPS 发病机制中具有关键作用和调节作用。骨折远端部位的维生素 K 缺乏是由于循环减少和减慢、肢体骨折或损伤后的局部固定以及使用维生素 K 储备在受伤肢体的远端部位和循环中促进骨折愈合和骨重塑。在骨折远端部位维生素 K 缺乏的情况下，经典炎症开始于远端组织无法被限制，经典炎症、缺氧变化、慢性缺血、神经源性炎症、交感神经调节，这些都是 CRPS 的发病机制，以及由于低羧化骨钙素水平较高而发生的斑片状骨质疏松症，都无法得到预防。简而言之，受伤肢体远端的维生素 K 水平下降，导致由于高水平的低羧化骨钙素而发生斑片状骨质疏松症，以及不受限制的炎症，这是 CRPS 发病和进展的原因。
