Departamento de Farmacología y Nutrición, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos., Avda. de Atenas s/n, 28922 Alcorcón, Madrid, Spain.
Pharmacol Biochem Behav. 2012 Aug;102(2):335-43. doi: 10.1016/j.pbb.2012.05.008. Epub 2012 May 17.
Diabetic neuropathy is a frequent complication of diabetes mellitus with a tremendous impact on patients' quality of life, and it remains poorly treated. Cannabinoids relieve the signs of diabetic neuropathy in different experimental models, including streptozotocin- (STZ-) induced type 1 diabetic rodents, and they may also relieve neuropathic signs in type 2 diabetic animals. This study compares the effect of the non-selective cannabinoid agonist WIN 55,212-2 (WIN) in Zucker Diabetic Fatty (ZDF) rats (type 2 diabetes) and in STZ-injected Wistar rats (type 1 diabetes). WIN (or its vehicle) was either systemically administered at a non-psychoactive dose or locally injected. Selective CB1 and CB2 cannabinoid antagonists were used to characterize WIN antineuropathic effects. Both type 1 and type 2 diabetic rats showed mechanical allodynia but not thermal hyperalgesia. WIN alleviated mechanical allodynia in both models of diabetes. In STZ-treated rats, both cannabinoid receptors were involved, whereas in ZDF rats, WIN effects seemed to mainly involve the activation of CB1 receptors. Higher doses of WIN were needed to significantly relieve mechanical allodynia upon intraplantar administration in ZDF vs. STZ-injected rats. Cannabinoids, acting on systemic and/or peripheral receptors, may serve as a new therapeutic alternative for symptom management in painful neuropathy associated with both type 1 and type 2 diabetes. Additionally, our results highlight the need for appropriate selection of diabetic experimental models because the results from studies in STZ-induced diabetic rodents might not be applicable in all diabetic situations.
糖尿病性神经病变是糖尿病的常见并发症，对患者的生活质量有重大影响，但治疗效果不佳。大麻素在不同的实验模型中缓解糖尿病性神经病变的症状，包括链脲佐菌素（STZ）诱导的 1 型糖尿病啮齿动物，并且它们也可能缓解 2 型糖尿病动物的神经病变症状。本研究比较了非选择性大麻素激动剂 WIN 55,212-2（WIN）在 Zucker 糖尿病肥胖（ZDF）大鼠（2 型糖尿病）和 STZ 注射 Wistar 大鼠（1 型糖尿病）中的作用。WIN（或其载体）以非精神活性剂量全身给药或局部注射。选择性 CB1 和 CB2 大麻素拮抗剂用于表征 WIN 的抗神经病变作用。1 型和 2 型糖尿病大鼠均表现出机械性痛觉过敏，但无热痛觉过敏。WIN 缓解了两种糖尿病模型的机械性痛觉过敏。在 STZ 处理的大鼠中，两种大麻素受体均参与其中，而在 ZDF 大鼠中，WIN 效应似乎主要涉及 CB1 受体的激活。与 STZ 注射大鼠相比，WIN 在足底内给药时需要更高剂量才能显著缓解机械性痛觉过敏。大麻素通过作用于全身和/或外周受体，可能成为 1 型和 2 型糖尿病相关痛性神经病变症状管理的新治疗选择。此外，我们的结果强调了适当选择糖尿病实验模型的必要性，因为 STZ 诱导的糖尿病啮齿动物研究的结果可能不适用于所有糖尿病情况。
