Miyagi Masayuki, Millecamps Magali, Danco Alexander T, Ohtori Seiji, Takahashi Kazuhisa, Stone Laura S
*Faculty of Dentistry †Alan Edwards Centre for Research on Pain, and ‡McGill Scoliosis & Spine Research Group, McGill University, Montreal, Quebec, Canada §Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan ¶Departments of Neurology & Neurosurgery ‖Anesthesiology and **Pharmacology & Therapeutics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
Spine (Phila Pa 1976). 2014 Aug 1;39(17):1345-54. doi: 10.1097/BRS.0000000000000334.
Immunohistochemical and behavioral study using the SPARC (secreted protein, acidic, rich in cysteine)-null mouse model of low back pain (LBP) associated with accelerated intervertebral disc (IVD) degeneration.
To determine if behavioral signs of LBP in SPARC-null mice are accompanied by sensory nervous system plasticity.
IVD pathology is a significant contributor to chronic LBP. In humans and rodents, decreased expression of SPARC is associated with IVD degeneration. We previously reported that SPARC-null mice exhibit age-dependent behavioral signs of chronic axial LBP and radiating leg pain.
SPARC-null and age-matched control young, middle-aged, and old mice (1.5, 6, and 24 mo of age, respectively) were evaluated. Cutaneous hind paw sensitivity to cold, heat, and mechanical stimuli were evaluated as measures of radiating pain. The grip force and tail suspension assays were performed to evaluate axial LBP. Motor impairment was assessed using an accelerating rotarod. IVD innervation was identified by immunohistochemistry targeting the nerve fiber marker PGP9.5 and the sensory neuropeptide calcitonin gene-related peptide (CGRP). Sensory nervous system plasticity was evaluated by quantification of CGRP- and neuropeptide-Y-immunoreactivity (-ir) in dorsal root ganglia neurons and CGRP-ir, GFAP-ir (astrocyte marker), and Iba-1-ir (microglia marker) in the spinal cord.
SPARC-null mice developed hypersensitivity to cold, axial discomfort, age-dependent motor impairment, age-dependent increases in sensory innervation in and around the IVDs, age-dependent upregulation of CGRP and neuropeptide-Y in dorsal root ganglia, and age-dependent upregulation of CGRP, microglia, and astrocytes in the spinal cord dorsal horn.
Increased innervation of degenerating IVDs by sensory nerve fibers and the neuroplasticity in sensory neurons and spinal cord could contribute to the underlying pathobiology of chronic discogenic LBP.
N/A.
使用与椎间盘退变加速相关的下腰痛（LBP）的富含半胱氨酸的酸性分泌蛋白（SPARC）基因敲除小鼠模型进行免疫组织化学和行为学研究。
确定SPARC基因敲除小鼠的LBP行为体征是否伴有感觉神经系统可塑性。
椎间盘病理学是慢性LBP的重要原因。在人类和啮齿动物中，SPARC表达降低与椎间盘退变有关。我们之前报道过，SPARC基因敲除小鼠表现出与年龄相关的慢性轴向LBP和放射性腿痛的行为体征。
对SPARC基因敲除小鼠和年龄匹配的对照小鼠（分别为1.5、6和24月龄的年轻、中年和老年小鼠）进行评估。评估后爪皮肤对冷、热和机械刺激的敏感性作为放射性疼痛的指标。进行握力和尾悬测试以评估轴向LBP。使用加速转棒试验评估运动功能障碍。通过针对神经纤维标记物PGP9.5和感觉神经肽降钙素基因相关肽（CGRP）的免疫组织化学鉴定椎间盘神经支配。通过定量背根神经节神经元中的CGRP和神经肽Y免疫反应性（-ir）以及脊髓中的CGRP-ir、GFAP-ir（星形胶质细胞标记物）和Iba-1-ir（小胶质细胞标记物）来评估感觉神经系统可塑性。
SPARC基因敲除小鼠出现对冷的超敏反应、轴向不适、与年龄相关的运动功能障碍、椎间盘及其周围感觉神经支配随年龄增加、背根神经节中CGRP和神经肽Y随年龄上调以及脊髓背角中CGRP、小胶质细胞和星形胶质细胞随年龄上调。
感觉神经纤维对退变椎间盘的神经支配增加以及感觉神经元和脊髓中的神经可塑性可能导致慢性盘源性LBP的潜在病理生物学过程。
无。
