Distinct calcitonin gene-related peptide expression pattern in primary afferents contribute to different neuropathic symptoms following chronic constriction or crush injuries to the rat sciatic nerve.
Distinct calcitonin gene-related peptide expression pattern in primary afferents contribute to different neuropathic symptoms following chronic constriction or crush injuries to the rat sciatic nerve.
复制标题
初级传入神经中不同的降钙素基因相关肽表达模式导致大鼠坐骨神经慢性收缩或挤压损伤后的不同神经病理症状
DOI：
10.1177/1744806916681566
复制
发表时间：
2016-01
期刊：
影响因子：
3.3
通讯作者：
Huang C
中科院分区：
文献类型：
--
作者：
Zou Y;Xu F;Tang Z;Zhong T;Cao J;Guo Q;Huang C
虽然降钙素基因相关肽是公认的疼痛传感器，降钙素基因相关肽在初级传入的表达可能受到不同类型的神经损伤后的差异。在这里，我们研究了是否不同的降钙素基因相关肽的表达模式在初级传入有助于不同的感觉障碍的坐骨神经损伤的三种动物模型：慢性压迫性损伤，轻度（100克力）或强烈（1000克力）的大鼠短暂挤压。对退缩反射和自发行为的评估表明，慢性压迫性损伤和轻度挤压导致阳性神经病性症状（静态/动态机械异常性疼痛、热痛觉过敏、冷异常性疼痛、自发性疼痛）。然而，强烈挤压导致阳性（动态机械异常性疼痛、冷异常性疼痛、自发性疼痛）和阴性症状（静态机械感觉减退、热痛觉减退）。降钙素基因相关肽在背根神经节和相应的脊髓节段的免疫反应，和降钙素基因相关肽在背根神经节的mRNA水平，表明，初级传入降钙素基因相关肽的供应显着减少后，强烈的挤压。这种减少阻止了阴性症状的发展（静态机械性感觉减退和热痛觉减退）。强烈挤压后鞘内注射外源性降钙素基因相关肽并不能改变热痛觉减退，但能改善静态机械感觉减退，这种作用可被降钙素基因相关肽受体拮抗剂阻断。因此，减少初级传入降钙素基因相关肽的供应会导致随后的阴性神经病症状，尤其是静态机械刺激。此外，神经损伤引起降钙素基因相关肽的亚细胞重新分布，从小型和中型的背根神经节神经元的大型背根神经节神经元，这阻碍了积极的神经病理症状的发展。鞘内注射降钙素基因相关肽受体拮抗剂可改善这些阳性症状，表明降钙素基因相关肽在大尺寸背根神经节神经元中的表达对于所有三种模型中的阳性神经病理性症状都很重要。两者合计，这些结果表明，不同的降钙素基因相关肽的表达模式在初级传入有助于不同的神经病理性症状慢性压迫或挤压损伤大鼠坐骨神经。
Although calcitonin gene-related peptide is a recognized pain transducer, the expression of calcitonin gene-related peptide in primary afferents may be differentially affected following different types of nerve injury. Here, we examined whether different calcitonin gene-related peptide expression patterns in primary afferents contributes to distinct sensory disturbances in three animal models of sciatic nerve injury: chronic constriction injury, mild (100g force) or strong (1000g force) transient crush in rats. Assessments of withdrawal reflexes and spontaneous behavior indicated that chronic constriction injury and mild crush resulted in positive neuropathic symptoms (static/dynamic mechanical allodynia, heat hyperalgesia, cold allodynia, spontaneous pain). However, strong crush led to both positive (dynamic mechanical allodynia, cold allodynia, spontaneous pain) and negative symptoms (static mechanical hypoesthesia, heat hypoalgesia). Calcitonin gene-related peptide immunoreactivity in dorsal root ganglia and corresponding spinal cord segments, and calcitonin gene-related peptide mRNA levels in dorsal root ganglia, indicated that the primary afferent calcitonin gene-related peptide supply was markedly reduced only after strong crush. This reduction paralleled the development of negative symptoms (static mechanical hypoesthesia and heat hypoalgesia). Administration of exogenous calcitonin gene-related peptide intrathecally after strong crush did not alter heat hypoalgesia but ameliorated static mechanical hypoesthesia, an effect blocked by a calcitonin gene-related peptide receptor antagonist. Thus, reducing the primary afferent calcitonin gene-related peptide supply contributed to subsequent negative neuropathic symptoms, especially to static mechanical stimuli. Moreover, nerve injury caused a subcellular redistribution of calcitonin gene-related peptide from small- and medium-size dorsal root ganglia neurons to large-size dorsal root ganglia neurons, which paralleled the development of positive neuropathic symptoms. Intrathecal administration of the calcitonin gene-related peptide receptor antagonist ameliorated these positive symptoms, indicating that the expression of calcitonin gene-related peptide in large-size dorsal root ganglia neurons is important for the positive neuropathic symptoms in all three models. Taken together, these results suggest that distinct calcitonin gene-related peptide expression pattern in primary afferents contribute to different neuropathic symptoms following chronic constriction or crush injuries to the rat sciatic nerve.
登录
查看更多内容
影响因子：
7.4
作者：
ATTAL, N;JAZAT, F;GUILBAUD, G
通讯作者：
GUILBAUD, G
影响因子：
5.3
作者：
Casals-Diaz, Laura;Vivo, Meritxell;Navarro, Xavier
通讯作者：
Navarro, Xavier
影响因子：
64.8
作者：
Chuang, HH;Prescott, ED;Julius, D
通讯作者：
Julius, D
影响因子：
2.5
作者：
CRIDLAND, RA;HENRY, JL
通讯作者：
HENRY, JL
影响因子：
5.3
作者：
Akkina, SK;Patterson, CL;Wright, DE
通讯作者：
Wright, DE