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己酮可可碱通过减轻微血管功能障碍来减轻慢性缺血后疼痛。

Pentoxifylline reduces chronic post-ischaemia pain by alleviating microvascular dysfunction.

作者信息

Ragavendran J Vaigunda, Laferrière A, Khorashadi M, Coderre T J

机构信息

Department of Anesthesia, McGill University, Montreal, Canada; Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada.

出版信息

Eur J Pain. 2014 Mar;18(3):406-14. doi: 10.1002/j.1532-2149.2013.00381.x. Epub 2013 Jul 31.

Abstract

BACKGROUND

Microvascular dysfunction and ischaemia in muscle play a role in the development of cutaneous tactile allodynia in chronic post-ischaemia pain (CPIP). Hence, studies were designed to assess whether pentoxifylline (PTX), a vasodilator and haemorrheologic agent, relieves allodynia in CPIP rats by alleviating microvascular dysfunction.

METHODS

Laser Doppler flowmetry of plantar blood flow was used to examine the effects of PTX on CPIP-induced alterations in post-occlusive reactive hyperaemia (reflecting microvascular dysfunction), and von Frey testing was used to examine its effects on CPIP-induced allodynia. Time-course effects of PTX on allodynia and microvascular dysfunction were assessed early (2-8 days) and late (18-25 days) post-ischaemia/reperfusion (I/R) injury, and its effects on allodynia were also tested at 30 days post-I/R injury.

RESULTS

PTX (25 mg/kg) produced significant anti-allodynic effects throughout the 21-day time course, but was not effective 30 days post-I/R injury. In laser Doppler studies, the reduced reactive hyperaemia in early CPIP rats was significantly improved by PTX (25 mg/kg). Conversely, treatment with PTX at the same dose did not affect reactive hyperaemia in late CPIP rats, likely since reactive hyperaemia was not significantly reduced pre-drug in these animals.

CONCLUSION

Since poor tissue perfusion underlies early stages of CPIP pain, the ameliorative effect of PTX on microvascular dysfunction might account for its anti-allodynic effect in our experimental model of complex regional pain syndrome type I.

摘要

背景

肌肉中的微血管功能障碍和缺血在慢性缺血后疼痛(CPIP)所致的皮肤触觉异常性疼痛的发生中起作用。因此,开展本研究以评估血管扩张剂及血液流变学药物己酮可可碱(PTX)是否通过减轻微血管功能障碍来缓解CPIP大鼠的异常性疼痛。

方法

采用激光多普勒血流仪测量足底血流量,以检测PTX对CPIP诱导的闭塞后反应性充血改变(反映微血管功能障碍)的影响,采用von Frey测试检测其对CPIP诱导的异常性疼痛的影响。在缺血/再灌注(I/R)损伤后的早期(2 - 8天)和晚期(18 - 25天)评估PTX对异常性疼痛和微血管功能障碍的时程效应,并在I/R损伤后30天测试其对异常性疼痛的影响。

结果

PTX(25 mg/kg)在整个21天的时程中均产生显著的抗异常性疼痛作用,但在I/R损伤后30天无效。在激光多普勒研究中,PTX(25 mg/kg)可显著改善早期CPIP大鼠降低的反应性充血。相反,相同剂量的PTX治疗对晚期CPIP大鼠的反应性充血无影响,可能是因为这些动物在用药前反应性充血未显著降低。

结论

由于组织灌注不良是CPIP疼痛早期的基础,PTX对微血管功能障碍的改善作用可能是其在我们的I型复杂性区域疼痛综合征实验模型中产生抗异常性疼痛作用的原因。

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本文引用的文献

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