Department of Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Japan.
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Japan.
Eur J Pharmacol. 2019 Apr 15;849:67-74. doi: 10.1016/j.ejphar.2019.02.002. Epub 2019 Feb 2.
Reduced blood flow in the skin is observed in patients with neuropathic pain and in animal models. The aim of the present study was to elucidate the relationship between reduced skin blood flow and neuropathic pain in mice with a chronic constriction injury (CCI). Noradrenaline-induced contraction was enhanced in isolated plantar arteries ipsilateral to the CCI surgery compared to the contralateral arteries. Ten μM hydralazine, a peripheral vasodilator, at improved the enhanced contractile response in the ipsilateral arteries. The plantar blood flow in vivo was lower on the ipsilateral side of the CCI mice than on the contralateral side, and a 50% paw withdrawal threshold, as measured using the von Frey filament test, was lower on the former than on the latter side. An intraperitoneal injection (i.p.) of hydralazine (1 mg/kg) or phentolamine (5 mg/kg) improved blood flow in the skin and hyperalgesia in the ipsilateral plantar. In adrenalectomized CCI mice, plantar blood flow in the skin on the ipsilateral side was increased compared to in sham-operated mice, which was accompanied by alleviation of hyperalgesia. Moreover, the enhanced contractile response to noradrenaline was also observed in the ipsilateral plantar arteries isolated from the adrenalectomized CCI mice. Either hydralazine (1 mg/kg, i.p.) or an adrenalectomy barely affected mean arterial pressure in the CCI mice, whereas phentolamine (5 mg/kg, i.p.) lowered it. These results suggest that reduced blood flow in the skin contributes to neuropathic pain and that improving that blood flow with peripheral vasodilators, such as hydralazine, can alleviate it.
皮肤血流量减少在神经病理性疼痛患者和动物模型中观察到。本研究的目的是阐明慢性缩窄性损伤（CCI）小鼠中皮肤血流量减少与神经病理性疼痛之间的关系。与对侧动脉相比，CCI 手术后同侧足底动脉中去甲肾上腺素诱导的收缩增强。10μM 肼屈嗪，一种外周血管扩张剂，改善了同侧动脉的增强收缩反应。CCI 小鼠对侧的足底血流量低于同侧，用冯弗雷尔丝测试测量的 50%爪退缩阈值也低于同侧。腹腔内注射肼屈嗪（1mg/kg）或酚妥拉明（5mg/kg）可改善同侧足底皮肤血流量和痛觉过敏。在肾上腺切除的 CCI 小鼠中，与假手术组相比，同侧皮肤的足底血流量增加，同时伴有痛觉过敏缓解。此外，还观察到从肾上腺切除的 CCI 小鼠同侧足底动脉中去甲肾上腺素的收缩反应增强。肼屈嗪（1mg/kg，腹腔内注射）或肾上腺切除术对 CCI 小鼠的平均动脉压几乎没有影响，而酚妥拉明（5mg/kg，腹腔内注射）则降低了它。这些结果表明，皮肤血流量减少导致神经病理性疼痛，用肼屈嗪等外周血管扩张剂改善血流量可以缓解疼痛。
