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Preventive hypothermia as a neuroprotective strategy for paclitaxel-induced peripheral neuropathy

Beh, Suet Thenga,b; Kuo, Yu-Minb; Chang, Wun-Shaing Waynec; Wilder-Smith, Einard,e,f; Tsao, Chia-Huia; Tsai, Chia-Huaa; Chen, Li-Tzongc; Liao, Lun-Dea,*

doi: 10.1097/j.pain.0000000000001547
Research Paper

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe adverse effect that occurs secondary to anticancer treatments and has no known preventive or therapeutic strategy. Therapeutic hypothermia has been shown to be effective in protecting against central and peripheral nervous system injuries. However, the effects of therapeutic hypothermia on CIPN have rarely been explored. We induced lower back hypothermia (LBH) in an established paclitaxel-induced CIPN rat model and found that the paclitaxel-induced impairments observed in behavioral, electrophysiological, and histological impairments were inhibited by LBH when applied at an optimal setting of 24°C to the sciatic nerve and initiated 90 minutes before paclitaxel infusion. Lower back hypothermia also inhibited the paclitaxel-induced activation of astroglia and microglia in the spinal cord and macrophage infiltration into and neuronal injury in the dorsal root ganglia and sciatic nerves. Furthermore, LBH decreased the local blood flow and local tissue concentrations of paclitaxel. Finally, in NOD/SCID mice inoculated with cancer cells, the antiproliferative effect of paclitaxel was not affected by the distal application of LBH. In conclusion, our findings indicate that early exposure to regional hypothermia alleviates paclitaxel-induced peripheral neuropathy. Therapeutic hypothermia may therefore represent an economical and nonpharmaceutical preventive strategy for CIPN in patients with localized solid tumors.

We provide the first evidence demonstrating that regional hypothermia is an effective and potential therapeutic strategy for alleviating paclitaxel-induced peripheral neuropathy.

aInstitute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli County, Taiwan

bInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan

cNational Institute of Cancer Research, National Health Research Institutes, Zhunan Town, Taiwan

dDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

eDepartment of Neurology, Kantonsspital Luzern, Luzern, Switzerland

fDepartment of Neurology, University of Bern, Bern, Switzerland

Corresponding author. Address: Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, No. 35, Keyan Rd, Zhunan, Miaoli County 35053, Taiwan. Tel.: 886-37-246166 #37125. E-mail address: (L.-D. Liao).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Y.-M. Kuo and L.-D. Liao contributed equally to this paper.

Received June 07, 2018

Received in revised form January 29, 2019

Accepted February 26, 2019

© 2019 International Association for the Study of Pain
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