Phenyl N-tert-butylnitrone, a Free Radical Scavenger, Reduces Mechanical Allodynia in Chemotherapy-induced Neuropathic Pain in Rats

• Published in: Anesthesiology (Philadelphia) 2010-02, Vol.112 (2), p.432-439
• Main Authors: HEE KEE KIM, YAN PING ZHANG, YOUNG SEOB GWAK, ABDI, Salahadin
• Format: Article
• Language: English
• Subjects: Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antineoplastic Agents - toxicity; Antineoplastic Agents, Phytogenic - toxicity; Behavior, Animal - drug effects; Biological and medical sciences; Body Weight - drug effects; Cyclic N-Oxides - pharmacology; Dose-Response Relationship, Drug; Free Radical Scavengers - pharmacology; Hypnotics and Sedatives; Male; Medical sciences; Neuroprotective Agents - pharmacology; Paclitaxel - toxicity; Pain - chemically induced; Pain - prevention & control; Pain - psychology; Pain Measurement - drug effects; Peripheral Nervous System Diseases - chemically induced; Peripheral Nervous System Diseases - prevention & control; Rats; Rats, Sprague-Dawley
• ISSN: 0003-3022; 1528-1175
• 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.