ArticleBrain, behavior, and immunity2014
A role for orexin in cytotoxic chemotherapy-induced fatigue.
Article in Brain, behavior, and immunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- 8 specific Chinese herbal injections combined with chemotherapy for breast cancer: a systematic review and network meta-analysis of comparative safety and efficacy.Frontiers in pharmacology · 2025Pooled it
- Trial
- Cancer therapy-related cognitive impairment, part 1: an integrative clinical-mechanistic framework from phenotypes to convergent neurobiological pathways.Pharmacological reports : PR · 2026Review
- Chronotherapeutic administration of neoadjuvant chemotherapy reduces cancer-related fatigue-like behavior.Brain, behavior, & immunity - health · 2026Article
- Prediction of Hyperinflammatory Phenotypes in Critically Ill Patients via Routine Clinical Data and IL-6: Towards Personalized Anti-Inflammatory Therapy.International journal of molecular sciences · 2025Article
- Comprehensive review of mouse models for studying cancer-related fatigue: Methods, findings and future directions (Review).Experimental and therapeutic medicine · 2025Review
- Article
- Chronic Fatigue in Cancer Survivorship: Psychiatry Versus Oncology or Psychiatry with Oncology?Current oncology reports · 2025Review
- Mechanistic insights into chemotherapy-induced circadian disruption using rodent models.Trends in neurosciences · 2025Review
- The metabolic basis of cancer-related fatigue.Neuroscience and biobehavioral reviews · 2025Review
- Quercetin attenuates cisplatin-induced fatigue through mechanisms associated with the regulation of the HPA axis and MCP-1 signaling.Frontiers in nutrition · 2025Article
- Seeing through "brain fog": neuroimaging assessment and imaging biomarkers for cancer-related cognitive impairments.Cancer imaging : the official publication of the International Cancer Imaging Society · 2024Review
- The role of orexin in fatigue and sleep quality in patients with primary Sjögren's syndrome.Zeitschrift fur Rheumatologie · 2024Article
- Article
- Microglia are implicated in the development of paclitaxel chemotherapy-associated cognitive impairment in female mice.Brain, behavior, and immunity · 2023Article
- Article
- Antibiotic treatment inhibits paclitaxel chemotherapy-induced activity deficits in female mice.PloS one · 2023Article
- Exercise protocols: The gap between preclinical and clinical exercise oncology studies.Metabolism open · 2022Article
- Sex differences in the behavioral and immune responses of mice to tumor growth and cancer therapy.Brain, behavior, and immunity · 2021Article
- Ganoderic acid alleviates chemotherapy-induced fatigue in mice bearing colon tumor.Acta pharmacologica Sinica · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Fatigue is the most common symptom related to cytotoxic chemotherapeutic treatment of cancer. Peripheral inflammation associated with cytotoxic chemotherapy is likely a causal factor of fatigue. The neural mechanisms by which cytotoxic chemotherapy associated inflammation induces fatigue behavior are not known. This lack of knowledge hinders development of interventions to reduce or prevent this disabling symptom. Infection induced fatigue/lethargy in rodents is mediated by suppression of hypothalamic orexin activity. Orexin is critical for maintaining wakefulness and motivated behavior. Though there are differences between infection and cytotoxic chemotherapy in some symptoms, both induce peripheral inflammation and fatigue. Based on these similarities we hypothesized that cytotoxic chemotherapy induces fatigue by disrupting orexin neuron activity. We found that a single dose of a cytotoxic chemotherapy cocktail (cyclophosphamide, adriamycin, 5-fluorouracil - CAF) induced fatigue/lethargy in mice and rats as evidenced by a significant decline in voluntary locomotor activity measured by telemetry. CAF induced inflammatory gene expression - IL-1R1 (p<0.001), IL-6 (p<0.01), TNFα (p<0.01), and MCP-1 (p<0.05) - in the rodent hypothalamus 6-24h after treatment during maximum fatigue/lethargy. CAF decreased orexin neuron activity as reflected by decreased nuclear cFos localization in orexin neurons 24h after treatment (p<0.05) and by decreased orexin-A in cerebrospinal fluid 16 h after treatment (p<0.001). Most importantly, we found that central administration of 1 μg orexin-A restored activity in CAF-treated rats (p<0.05). These results demonstrate that cytotoxic chemotherapy induces hypothalamic inflammation and that suppression of hypothalamic orexin neuron activity has a causal role in cytotoxic chemotherapy-induced fatigue in rodents.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.