Anti-hyperalgesic effects of calcitonin on neuropathic pain interacting with its peripheral receptors.
Anti-hyperalgesic effects of calcitonin on neuropathic pain interacting with its peripheral receptors.
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DOI：
10.1186/1744-8069-8-42
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发表时间：
2012-06-07
期刊：
影响因子：
3.3
通讯作者：
Yoshimura M
中科院分区：
文献类型：
--
作者：
Ito A;Takeda M;Yoshimura T;Komatsu T;Ohno T;Kuriyama H;Matsuda A;Yoshimura M
多肽激素降钙素在临床上以其缓解神经性疼痛如椎管狭窄、糖尿病性神经病变和复杂性区域疼痛综合征的能力而闻名。然而，其镇痛作用的机制仍不清楚。在此，我们研究了降钙素在大鼠神经病理性疼痛模型中的抗痛觉过敏作用的机制。皮下注射鳗鱼降钙素的衍生物elcatonin可减轻慢性压迫性损伤（CCI）引起的痛敏。实时荧光定量逆转录聚合酶链反应（RT-PCR）结果显示，CCI可引起同侧背根神经节（DRG）河豚毒素（TTX）敏感的Nav1.3 mRNA表达上调，而TTX抗性的Nav1.8和Nav1.9 mRNA表达下调，从而增加周围神经的兴奋性。这些变化被elcatonin逆转。此外，降钙素受体和125 I-降钙素结合位点的基因表达增加，在收缩的周围神经组织，但不是在DRG。依降钙素的抗痛敏作用和钠通道mRNA的正常化与降钙素受体表达的变化是平行的。而依降钙素在正常情况下对降钙素受体mRNA表达有抑制作用，但不影响伤害性感受的敏感性和钠通道的基因表达。这些结果表明，降钙素对CCI大鼠的抗痛觉过敏作用可能归因于钠通道表达的正常化，这可能是由外周神经组织产生的未知信号而不是由背根神经元通过激活降钙素受体产生的信号发挥作用。降钙素信号在正常情况下是沉默的，神经损伤可能是沉默信号转化为活跃信号的触发因素之一。
The polypeptide hormone calcitonin is clinically well known for its ability to relieve neuropathic pain such as spinal canal stenosis, diabetic neuropathy and complex regional pain syndrome. Mechanisms for its analgesic effect, however, remain unclear. Here we investigated the mechanism of anti-hyperalgesic action of calcitonin in a neuropathic pain model in rats. Subcutaneous injection of elcatonin, a synthetic derivative of eel calcitonin, relieved hyperalgesia induced by chronic constriction injury (CCI). Real-time reverse transcriptase-polymerase chain reaction analysis revealed that the CCI provoked the upregulation of tetrodotoxin (TTX)-sensitive Nav.1.3 mRNA and downregulation of TTX-resistant Nav1.8 and Nav1.9 mRNA on the ipsilateral dorsal root ganglion (DRG), which would consequently increase the excitability of peripheral nerves. These changes were reversed by elcatonin. In addition, the gene expression of the calcitonin receptor and binding site of 125I-calcitonin was increased at the constricted peripheral nerve tissue but not at the DRG. The anti-hyperalgesic effect and normalization of sodium channel mRNA by elcatonin was parallel to the change of the calcitonin receptor expression. Elcatonin, however, did not affect the sensitivity of nociception or gene expression of sodium channel, while it suppressed calcitonin receptor mRNA under normal conditions. These results suggest that the anti-hyperalgesic action of calcitonin on CCI rats could be attributable to the normalization of the sodium channel expression, which might be exerted by an unknown signal produced at the peripheral nerve tissue but not by DRG neurons through the activation of the calcitonin receptor. Calcitonin signals were silent in the normal condition and nerve injury may be one of triggers for conversion of a silent to an active signal.
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影响因子：
2.3
作者：
Takayama B;Kikuchi S;Konno S;Sekiguchi M
通讯作者：
Sekiguchi M
影响因子：
7
作者：
Gibson, UEM;Heid, CA;Williams, PM
通讯作者：
Williams, PM
影响因子：
7
作者：
Heid, CA;Stevens, J;Williams, PM
通讯作者：
Williams, PM
影响因子：
4.8
作者：
Suzuki, H;Nakamura, I;Suda, T
通讯作者：
Suda, T
DOI：
10.1016/0011-393x(95)85007-4
发表时间：
1995-04-01
影响因子：
1.9
作者：
JIMENEZ, FE;ALBIZURI, JMA;CANALES, AG
通讯作者：
CANALES, AG