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Phenyl N-tert-butylnitrone, a free radical scavenger, reduces mechanical allodynia in chemotherapy-induced neuropathic pain in rats.
Anesthesiology. 2010 Feb; 112(2):432-9.A

Abstract

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.

Authors+Show Affiliations

Department of Anesthesiology, Perioperative Medicine, and Pain Management, University of Miami, LM Miller School of Medicine, 1011 Northwest 15th Street, Miami, Florida 33136, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20068451

Citation

Kim, Hee Kee, et al. "Phenyl N-tert-butylnitrone, a Free Radical Scavenger, Reduces Mechanical Allodynia in Chemotherapy-induced Neuropathic Pain in Rats." Anesthesiology, vol. 112, no. 2, 2010, pp. 432-9.
Kim HK, Zhang YP, Gwak YS, et al. Phenyl N-tert-butylnitrone, a free radical scavenger, reduces mechanical allodynia in chemotherapy-induced neuropathic pain in rats. Anesthesiology. 2010;112(2):432-9.
Kim, H. K., Zhang, Y. P., Gwak, Y. S., & Abdi, S. (2010). Phenyl N-tert-butylnitrone, a free radical scavenger, reduces mechanical allodynia in chemotherapy-induced neuropathic pain in rats. Anesthesiology, 112(2), 432-9. https://doi.org/10.1097/ALN.0b013e3181ca31bd
Kim HK, et al. Phenyl N-tert-butylnitrone, a Free Radical Scavenger, Reduces Mechanical Allodynia in Chemotherapy-induced Neuropathic Pain in Rats. Anesthesiology. 2010;112(2):432-9. PubMed PMID: 20068451.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phenyl N-tert-butylnitrone, a free radical scavenger, reduces mechanical allodynia in chemotherapy-induced neuropathic pain in rats. AU - Kim,Hee Kee, AU - Zhang,Yan Ping, AU - Gwak,Young Seob, AU - Abdi,Salahadin, PY - 2010/1/14/entrez PY - 2010/1/14/pubmed PY - 2010/2/20/medline SP - 432 EP - 9 JF - Anesthesiology JO - Anesthesiology VL - 112 IS - 2 N2 - 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. SN - 1528-1175 UR - https://www.unboundmedicine.com/medline/citation/20068451/Phenyl_N_tert_butylnitrone_a_free_radical_scavenger_reduces_mechanical_allodynia_in_chemotherapy_induced_neuropathic_pain_in_rats_ L2 - https://pubs.asahq.org/anesthesiology/article-lookup/doi/10.1097/ALN.0b013e3181ca31bd DB - PRIME DP - Unbound Medicine ER -