2. Academic Validation
  3. Taltirelin alleviates fatigue-like behavior in mouse models of cancer-related fatigue

Taltirelin alleviates fatigue-like behavior in mouse models of cancer-related fatigue

  • Pharmacol Res. 2017 Oct:124:1-8. doi: 10.1016/j.phrs.2017.07.012.
John P Dougherty 1,  Brian S Wolff 2,  Mary J Cullen 3,  Leorey N Saligan 4,  Marvin C Gershengorn 5
Affiliations

Affiliations

  • 1 National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. Electronic address: john.dougherty@nih.gov.
  • 2 National Institute of Nursing Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. Electronic address: brian.wolff@nih.gov.
  • 3 National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. Electronic address: mary.cullen@nih.gov.
  • 4 National Institute of Nursing Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA,. Electronic address: saliganl@mail.nih.gov.
  • 5 National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. Electronic address: marving@mail.nih.gov.
PMID: 28720519 DOI: 10.1016/j.phrs.2017.07.012
Abstract

Fatigue affects most Cancer patients and has numerous potential causes, including Cancer itself and Cancer treatment. Cancer-related fatigue (CRF) is not relieved by rest, can decrease quality of life, and has no FDA-approved therapy. Thyrotropin-releasing hormone (TRH) has been proposed as a potential novel treatment for CRF, but its efficacy against CRF remains largely untested. Thus, we tested the TRH analog, taltirelin (TAL), in mouse models of CRF. To model fatigue, we used a mouse model of chemotherapy, a mouse model of radiation therapy, and mice bearing colon 26 carcinoma tumors. We used the treadmill fatigue test to assess fatigue-like behavior after treatment with TAL. Additionally, we used wild-type and TRH receptor knockout mice to determine which TRH receptor was necessary for the actions of TAL. Tumor-bearing mice displayed muscle wasting and all models caused fatigue-like behavior, with mice running a shorter distance in the treadmill fatigue test than controls. TAL reversed fatigue-like behavior in all three models and the mouse TRH1 receptor was necessary for the effects of TAL. These data suggest that TAL may be useful in alleviating fatigue in all Cancer patients and provide further support for evaluating TAL as a potential therapy for CRF in humans.

Keywords

Cancer-related fatigue; Colon 26 carcinoma; Mouse fatigue model; Muscle wasting; Radiation-induced fatigue; Treadmill fatigue test; Treadmill running.

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