Laboratory for Development Pharmacology, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni City, Shizuoka 410-2321, Japan.
Fundam Clin Pharmacol. 2012 Jun;26(3):315-21. doi: 10.1111/j.1472-8206.2011.00934.x. Epub 2011 Mar 11.
In addition to its regulatory effect on bone mass, calcitonin has been shown to relieve pain and alleviate peripheral circulatory disturbance in patients with Raynaud's syndrome and complex regional pain syndrome. In the present study, we investigated whether calcitonin ameliorates diminished blood flow and enhanced arterial contraction in response to noradrenaline in chronic constriction injury (CCI) of the sciatic nerve in rats. Following surgically induced CCI, laser Doppler flowmetry studies showed a significant decrease in plantar skin blood flow of the ipsilateral hind paw compared to the contralateral side. A subcutaneous bolus injection of elcatonin (20 U/kg), a synthetic derivative of eel calcitonin, significantly improved decreased skin blood flow in the ipsilateral side. In vitro analysis of plantar arteries isolated from the ipsilateral hind paw 7-13 days after the CCI procedure showed higher sensitivity to noradrenaline than the plantar arteries from the contralateral side. Elcatonin (0.1-10 nm) significantly reduced noradrenaline-induced contraction in the arteries of the ipsilateral side, whereas it had little effect on those of the contralateral side. These results suggest that calcitonin selectively ameliorates enhanced arterial contractility in CCI neuropathic rats, thus leading to its alleviating effect on peripheral circulatory disturbance.
除了对骨量的调节作用外，降钙素已被证明可缓解雷诺氏综合征和复杂性区域疼痛综合征患者的疼痛和外周循环障碍。在本研究中，我们研究了降钙素是否可以改善慢性坐骨神经结扎损伤（CCI）大鼠对去甲肾上腺素反应的血流减少和动脉收缩增强。在手术诱导的 CCI 后，激光多普勒血流仪研究显示，与对侧相比，同侧后爪足底皮肤血流量明显减少。鳗鱼降钙素的合成衍生物（20 U/kg）皮下推注降钙素可显著改善同侧皮肤血流量减少。CCI 术后 7-13 天从同侧后爪分离的足底动脉的体外分析显示，对去甲肾上腺素的敏感性高于对侧的足底动脉。降钙素（0.1-10nm）可显著降低同侧动脉中去甲肾上腺素诱导的收缩，而对侧动脉几乎没有影响。这些结果表明，降钙素选择性改善 CCI 神经病理性大鼠增强的动脉收缩性，从而减轻其对外周循环障碍的缓解作用。
