Instituto de Farmacologia e Terapêutica, Faculdade de Medicina, Universidade do Porto, Portugal.
J Pain. 2011 Feb;12(2):194-204. doi: 10.1016/j.jpain.2010.06.009. Epub 2010 Aug 23.
Hypertension-associated hypoalgesia is widely recognized in acute pain conditions. In chronic pain states, however, the relationship between blood pressure and pain sensitivity is still ill-defined, with different authors reporting negative, positive, or even no relationship at all. This work addresses this issue, using complete Freund's adjuvant (CFA)-induced monoarthritis in different models of hypertension: Spontaneous (spontaneously hypertensive rats, SHR), induced by infusion of angiotensin II (ANG) or 1,3-dipropyl-8-sulfophenylxanthine (DPSPX, an adenosine receptors' antagonist), and renal artery ligation (RAL). Nociceptive responses associated with monoarthritis were evaluated by different behavioral tests (von Frey, ankle-bend and CatWalk) and by quantification of Fos expression at the dorsal horn upon noxious stimulation. In all hypertension models, higher von Frey thresholds and lower Fos expression were detected in hypertensive rats with chronic inflammatory pain, as compared to normotensive monoarthritic rats. In SHR and DPSPX, but not ANG or RAL models, hypertensive animals displayed lower inflammation than normotensives. Ankle-bend and CatWalk results indicated lower pain sensitivity in hypertensive rats only in SHR and DPSPX models. The present study shows the importance of using multiple models of hypertension, and evaluating pain responses by various methods, to better understand the complexity of the interactions between pain and cardiovascular regulatory systems.
This study used different models of hypertension to investigate whether chronic pain alters the normal integration of cardiovascular and pain regulatory systems. A complete understanding of the mechanisms underlying the complex interactions between these systems may disclose future therapeutic approaches to treat hypertension/chronic pain comorbidity states.
高血压相关的痛觉减退在急性疼痛情况下被广泛认识。然而，在慢性疼痛状态下，血压与疼痛敏感性之间的关系仍不清楚，不同的作者报告了负相关、正相关甚至没有相关性。本研究通过不同的高血压模型（自发性高血压大鼠（SHR）、血管紧张素 II 输注（ANG）或 1,3-二丙基-8-磺苯基黄嘌呤（DPSPX，一种腺苷受体拮抗剂）诱导的、肾动脉结扎（RAL））所致完全弗氏佐剂（CFA）诱导的单关节炎，解决了这一问题。通过不同的行为学测试（von Frey、踝关节弯曲和 CatWalk）和有害刺激时背角 Fos 表达的定量评估与单关节炎相关的伤害性反应。在所有高血压模型中，与正常血压单关节炎大鼠相比，慢性炎症性疼痛的高血压大鼠的 von Frey 阈值更高，Fos 表达更低。在 SHR 和 DPSPX 模型中，但在 ANG 或 RAL 模型中，高血压动物的炎症程度低于正常血压动物。踝关节弯曲和 CatWalk 结果表明，只有在 SHR 和 DPSPX 模型中，高血压大鼠的疼痛敏感性较低。本研究表明，使用多种高血压模型并通过多种方法评估疼痛反应对于更好地理解疼痛和心血管调节系统之间相互作用的复杂性非常重要。
本研究使用不同的高血压模型来研究慢性疼痛是否改变了心血管和疼痛调节系统的正常整合。对这些系统之间复杂相互作用的潜在机制的全面理解可能会揭示未来治疗高血压/慢性疼痛共病状态的治疗方法。
