Phenyl N-tert-butylnitrone, a Free Radical Scavenger, Reduces Mechanical Allodynia in Chemotherapy-induced Neuropathic Pain in Rats.
Kim, Hee Kee Ph.D. *; Zhang, Yan Ping Ph.D. +; Gwak, Young Seob Ph.D. ++; Abdi, Salahadin M.D., Ph.D. [S]
112(2):432-439, February 2010.
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Background: 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.
Methods: Neuropathic pain was induced by intraperitoneal injection of paclitaxel (2 mg/kg) on four alternate days (days 0, 2, 4, and 6) in male Spraue-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.
Results: 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.
Conclusions: 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.
(C) 2010 American Society of Anesthesiologists, Inc.