Ragavendran J Vaigunda, Laferrière A, Khorashadi M, Coderre T J
Department of Anesthesia, McGill University, Montreal, Canada; Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada.
Eur J Pain. 2014 Mar;18(3):406-14. doi: 10.1002/j.1532-2149.2013.00381.x. Epub 2013 Jul 31.
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.
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.
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.
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.
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。
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。
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。
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。