Phenyl N-tert-butylnitrone, a free radical scavenger, reduces mechanical allodynia in chemotherapy-induced neuropathic pain in rats.
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 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.


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.
Kim
Hee Kee
HK
Department of Anesthesiology, Perioperative Medicine, and Pain Management, University of Miami, LM Miller School of Medicine, 1011 Northwest 15th Street, Miami, Florida 33136, USA.
Zhang
Yan Ping
YP
Gwak
Young Seob
YS
Abdi
Salahadin
S
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006993:Hypnotics and Sedatives; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017239:Paclitaxel / Q000633:toxicity; D010146:Pain / Q000139:chemically induced* / Q000517:prevention & control* / Q000523:psychology; D010147:Pain Measurement / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D006993:Hypnotics and Sedatives; D018696:Neuroprotective Agents; C029217:phenyl-N-tert-butylnitrone; D017239:Paclitaxel