The Role of Inflammation in the Pain, Fatigue, and Sleep Disturbance Symptom Cluster in Advanced Cancer

J Pain Symptom Manage. 2018 May;55(5):1286-1295. doi: 10.1016/j.jpainsymman.2018.01.008. Epub 2018 Jan 31.

Abstract

Context: Symptom researchers have proposed a model of inflammatory cytokine activity and dysregulation in cancer to explain co-occurring symptoms including pain, fatigue, and sleep disturbance.

Objectives: We tested the hypothesis that psychological stress accentuates inflammation and that stress and inflammation contribute to one's experience of the pain, fatigue, and sleep disturbance symptom cluster (symptom cluster severity, symptom cluster distress) and its impact (symptom cluster interference with daily life, quality of life).

Methods: We used baseline data from a symptom cluster management trial. Adult participants (N = 158) receiving chemotherapy for advanced cancer reported pain, fatigue, and sleep disturbance on enrollment. Before intervention, participants completed measures of demographics, perceived stress, symptom cluster severity, symptom cluster distress, symptom cluster interference with daily life, and quality of life and provided a blood sample for four inflammatory biomarkers (interleukin-1β, interleukin-6, tumor necrosis factor-α, and C-reactive protein).

Results: Stress was not directly related to any inflammatory biomarker. Stress and tumor necrosis factor-α were positively related to symptom cluster distress, although not symptom cluster severity. Tumor necrosis factor-α was indirectly related to symptom cluster interference with daily life, through its effect on symptom cluster distress. Stress was positively associated with symptom cluster interference with daily life and inversely with quality of life. Stress also had indirect effects on symptom cluster interference with daily life, through its effect on symptom cluster distress.

Conclusion: The proposed inflammatory model of symptoms was partially supported. Investigators should test interventions that target stress as a contributing factor in co-occurring pain, fatigue, and sleep disturbance and explore other factors that may influence inflammatory biomarker levels within the context of an advanced cancer diagnosis and treatment.

Keywords: Cancer; inflammation; psychological stress; quality of life; symptom cluster.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Biomarkers / blood
  • Cognitive Behavioral Therapy
  • Fatigue / epidemiology
  • Fatigue / immunology*
  • Fatigue / therapy
  • Female
  • Humans
  • Inflammation / blood*
  • Inflammation / epidemiology
  • Inflammation / therapy
  • Male
  • Middle Aged
  • Models, Biological
  • Neoplasms / drug therapy
  • Neoplasms / epidemiology
  • Neoplasms / immunology*
  • Neoplasms / psychology
  • Pain / epidemiology
  • Pain / immunology*
  • Pain Management
  • Quality of Life
  • Sleep Wake Disorders / epidemiology
  • Sleep Wake Disorders / immunology*
  • Sleep Wake Disorders / therapy
  • Stress, Psychological / epidemiology
  • Stress, Psychological / immunology*
  • Stress, Psychological / therapy

Substances

  • Antineoplastic Agents
  • Biomarkers