C-Reactive Protein and Its Relationship with Pain in Patients with Advanced Cancer Cachexia: Secondary Cross-Sectional Analysis of a Multicenter Prospective Cohort Study

Abstract

Background: Limited information is available on the relationship between C-reactive protein (CRP) levels and pain in advanced cancer. Objectives: To investigate the relationship between serum levels of CRP and subtypes of pain. Design: A secondary cross-sectional analysis of a prospective cohort study. Setting/Subjects: Patients with advanced cancer admitted to 23 palliative care units in Japan. Measurements: Patients rated the severity of pain on the numerical rating scale (NRS) and physicians evaluated pain on the integrated palliative care outcome scale (IPOS). Physicians assessed neuropathic pain and breakthrough pain based on their presence or absence. Patients were divided into four groups according to CRP levels. Comparisons were performed using the Kruskal-Wallis test or chi-squared test. To evaluate the relationship between CRP and subtypes of pain, adjusted odds ratios (ORs) and 95% confidence intervals (CIs) in logistic models were calculated. Results: We divided 1513 patients into four groups: low CRP (n = 234), moderate CRP (n = 513), high CRP (n = 352), and very high CRP (n = 414). Spearman's correlation coefficient between CRP and pain NRS and that between CRP and pain IPOS were 0.15 (p < 0.001) and 0.16 (p < 0.001), respectively. In the models of pain NRS

Cancer cachexia: Pathophysiology and association with cancer-related pain

“…Pain assessed at baseline via the pain subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 (EORTC QLQ-C30) was significantly associated with C-reactive protein (CRP), a hepatic secretory protein associated with systemic inflammation ( 56 ). These findings were confirmed in a more recent study of 1,513 advanced cancer patients, which found patients in the highest quartile of CRP values had significantly increased pain compared to those in the lowest quartile ( 57 ). Moreover, another study identified high serum IL-6 concentrations in non-responders to the pain medication tramadol, which resulted in the use of stronger opioids in this group of patients ( 58 ).…”

“…pain compared to those in the lowest quartile (57). Moreover, another study identified high serum IL-6 concentrations in nonresponders to the pain medication tramadol, which resulted in the use of stronger opioids in this group of patients (58).…”

Psychological symptoms of illness and emotional distress in advanced cancer cachexia

“…The CNS is directly affected by inflammatory mediators in sickness, and the brain mediates cluster of behavioral changes (e.g., sleep disruption, cognitive impairment and memory deficits, disorientation, and reduction in motivated behavior) through communication systems between the immune system and the brain in humans and animals [20]. Other outcomes of sickness behavior, including weight loss (reduction of skeletal muscle mass and fat mass), increased catabolism (increased and lipolysis), circadian rhythm disorders (disarrangement eating habits and sleep-wake cycles), social disinterest, and sexual disinterest, appear to be a part of an integrated response of CNS and systemic inflammation , 5,6,19,20]. Accordingly, cancer cachexia has many overlapping features of sickness behavior.…”

“…The CNS is directly affected by inflammatory mediators in sickness, and the brain mediates cluster of behavioral changes (e.g., sleep disruption, cognitive impairment and memory deficits, disorientation, and reduction in motivated behavior) through communication systems between the immune system and the brain in humans and animals [20]. Other outcomes of sickness behavior, including weight loss (reduction of skeletal 5,6,19,20]. Accordingly, cancer cachexia has many overlapping features of sickness behavior.…”

“…Patients with cancer experience various symptoms of cachexia and these may be broadly characterized as physical (e.g., fever, pain) and psychological symptoms of illness (e.g., drowsiness, depression); these symptoms are summarized in Table 1[2,3,4 ▪▪ ,5]. The distinction (physical versus psychological) is not absolute and for example, anorexia and fatigue can arise as a direct consequence of tumor-induced neuro-inflammation but also can occur secondary to depressed mood.…”