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

Suet Theng Beh, Yu-Min Kuo, Wun Shaing Wayne Chang, Einar Wilder-Smith, Chia Hui Tsao, Chia Hua Tsai, Li Tzong Chen, Lun De Liao

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1505-1521
Number of pages17
JournalPain
Volume160
Issue number7
DOIs
Publication statusPublished - 2019 Jul 1

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Peripheral Nervous System Diseases
Paclitaxel
Hypothermia
Induced Hypothermia
Drug Therapy
Sciatic Nerve
Nervous System Trauma
Inbred NOD Mouse
SCID Mice
Peripheral Nervous System
Spinal Ganglia
Microglia
Astrocytes
Neoplasms
Spinal Cord
Central Nervous System
Macrophages
Wounds and Injuries
Therapeutics

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

Cite this

Beh, S. T., Kuo, Y-M., Chang, W. S. W., Wilder-Smith, E., Tsao, C. H., Tsai, C. H., ... Liao, L. D. (2019). Preventive hypothermia as a neuroprotective strategy for paclitaxel-induced peripheral neuropathy. Pain, 160(7), 1505-1521. https://doi.org/10.1097/j.pain.0000000000001547
Beh, Suet Theng ; Kuo, Yu-Min ; Chang, Wun Shaing Wayne ; Wilder-Smith, Einar ; Tsao, Chia Hui ; Tsai, Chia Hua ; Chen, Li Tzong ; Liao, Lun De. / Preventive hypothermia as a neuroprotective strategy for paclitaxel-induced peripheral neuropathy. In: Pain. 2019 ; Vol. 160, No. 7. pp. 1505-1521.
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abstract = "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.",
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Beh, ST, Kuo, Y-M, Chang, WSW, Wilder-Smith, E, Tsao, CH, Tsai, CH, Chen, LT & Liao, LD 2019, 'Preventive hypothermia as a neuroprotective strategy for paclitaxel-induced peripheral neuropathy', Pain, vol. 160, no. 7, pp. 1505-1521. https://doi.org/10.1097/j.pain.0000000000001547

Preventive hypothermia as a neuroprotective strategy for paclitaxel-induced peripheral neuropathy. / Beh, Suet Theng; Kuo, Yu-Min; Chang, Wun Shaing Wayne; Wilder-Smith, Einar; Tsao, Chia Hui; Tsai, Chia Hua; Chen, Li Tzong; Liao, Lun De.

In: Pain, Vol. 160, No. 7, 01.07.2019, p. 1505-1521.

Research output: Contribution to journalArticle

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T1 - Preventive hypothermia as a neuroprotective strategy for paclitaxel-induced peripheral neuropathy

AU - Beh, Suet Theng

AU - Kuo, Yu-Min

AU - Chang, Wun Shaing Wayne

AU - Wilder-Smith, Einar

AU - Tsao, Chia Hui

AU - Tsai, Chia Hua

AU - Chen, Li Tzong

AU - Liao, Lun De

PY - 2019/7/1

Y1 - 2019/7/1

N2 - 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.

AB - 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.

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