Department of Anesthesiology, Perioperative Medicine, and Pain Management, University of Miami, LM Miller School of Medicine, 1011 Northwest 15th Street, Miami, Florida 33136, USA.
Anesthesiology. 2010 Feb;112(2):432-9. doi: 10.1097/ALN.0b013e3181ca31bd.
Paclitaxel is a widely used chemotherapeutic drug for breast and ovarian cancer. Unfortunately, it induces neuropathic pain, which is a dose-limiting side effect. Free radicals have been implicated in many neurodegenerative diseases. The current study tests the hypothesis that a free radical scavenger plays an important role in reducing chemotherapy-induced neuropathic pain.
Neuropathic pain was induced by intraperitoneal injection of paclitaxel (2 mg/kg) on four alternate days (days 0, 2, 4, and 6) in male Sprague-Dawley rats. Phenyl N-tert-butylnitrone (PBN), a free radical scavenger, was administered intraperitoneally as a single dose or multiple doses before or after injury. Mechanical allodynia was measured by using von Frey filaments.
The administration of paclitaxel induced mechanical allodynia, which began to manifest on days 7-10, peaked within 2 weeks, and plateaued for at least 2 months after the first paclitaxel injection. A single injection or multiple intraperitoneal injections of PBN ameliorated paclitaxel-induced pain behaviors in a dose-dependent manner. Further, multiple administrations of PBN starting on day 7 through day 15 after the first injection of paclitaxel completely prevented the development of mechanical allodynia. However, an intraperitoneal administration of pbn for 8 days starting with the first paclitaxel injection did not prevent the development of pain behavior.
This study clearly shows that PBN alleviated mechanical allodynia induced by paclitaxel in rats. Furthermore, our data show that PBN given on days 7 through 15 after the first paclitaxel injection prevented the development of chemotherapy-induced neuropathic pain. This clearly has a clinical implication.
紫杉醇是一种广泛用于乳腺癌和卵巢癌的化疗药物。不幸的是，它会引起神经性疼痛，这是一种剂量限制的副作用。自由基与许多神经退行性疾病有关。本研究检验了自由基清除剂在减轻化疗引起的神经性疼痛中起重要作用的假设。
雄性 Sprague-Dawley 大鼠通过腹腔注射紫杉醇（2mg/kg）在四个交替日（第 0、2、4 和 6 天）诱导神经性疼痛。自由基清除剂苯甲硝酮（PBN）在损伤前或损伤后单次或多次腹腔内给药。使用 von Frey 纤维测量机械性痛觉过敏。
紫杉醇的给药引起机械性痛觉过敏，从第 7-10 天开始表现出来，在 2 周内达到高峰，并在第一次紫杉醇注射后至少 2 个月内保持稳定。单次注射或多次腹腔内注射 PBN 以剂量依赖性方式改善紫杉醇引起的疼痛行为。此外，从第一次紫杉醇注射后第 7 天开始至第 15 天多次给予 PBN 完全阻止了机械性痛觉过敏的发展。然而，从第一次紫杉醇注射开始连续 8 天腹腔内给予 PBN 并不能预防疼痛行为的发生。
本研究清楚地表明，PBN 减轻了紫杉醇诱导的大鼠机械性痛觉过敏。此外，我们的数据表明，在第一次紫杉醇注射后第 7-15 天给予 PBN 可预防化疗引起的神经性疼痛的发展。这显然具有临床意义。
