Chronic Pain in Patients With Chronic Kidney Disease in Hemodialysis

Chronic Kidney Disease (CKD) has an estimated prevalence ranging from 13.4% to 10.6% across stages 1 to 5. These data indicate that CKD is recognized as a major global health issue, with high healthcare costs. Its incidence increases with age, with individuals over 65 years old comprising 40% of CKD patients. Gender differences exist, with males being more affected, although females exhibit greater frailty and severity. This population often presents high comorbidity with other conditions such as diabetes, hypertension, and cardiovascular diseases, along with malnutrition, sedentary lifestyles, poor health-related quality of life, low functional capacity, frailty, high levels of dependency, and, recently evidenced, pain. All of these factors are associated with increased mortality risk, exceeding 15% annually. Cardiovascular disease is the leading cause of death in patients with advanced CKD and a significant risk factor for peripheral arterial disease and lower limb amputation.

Chronic pain imposes a significant personal and economic burden, affecting over 30% of people worldwide. Unlike acute pain, which serves a protective function, chronic pain may be better considered as a disease itself, with both physical and psychological implications. There has been a growing acceptance of the biopsychosocial model in addressing patients with chronic pain, understanding pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage," according to the International Association for the Study of Pain (IASP). This perspective considers pain not only as a purely nociceptive experience but also as a personal experience involving both biological and emotional/psychological components.

Pain is one of the most common symptoms among patients with end-stage CKD, often going unrecognized or inadequately managed. Barriers to proper pain management include limited awareness of the problem, inadequate medical education, and common misconceptions about the inevitability of pain in older adults and HD patients. More than 50% of hemodialysis patients suffer from pain, with 75% of them receiving ineffective treatment due to healthcare professionals' lack of awareness of this symptom. Therefore, pain management in this population is a complex and challenging task. The most prevalent pain syndromes in hemodialysis patients include musculoskeletal disorders, metabolic neuropathies, and typical intradialytic puncture pain.

Patients with chronic pain from musculoskeletal disorders have been shown to exhibit high levels of catastrophizing, fear of movement, anxiety, depression, sleep disturbances, and elevated salivary cortisol levels due to the stress caused by chronic pain and the prevalence of musculoskeletal disorders as potential causes of pain in CKD patients.

Hormonal alterations at the hypothalamic-pituitary axis (HPA) level are frequently observed with worsening renal function. Traditionally, these alterations have been understood as a consequence of renal insufficiency. However, recent evidence suggests the involvement of such hormonal disorders in the genesis of CKD. The HPA axis controls stress responses through a negative feedback mechanism. If chronic pain is considered a stressor, a reciprocal response is triggered, with increased pain activating physiological mechanisms responding to stress, such as elevated cortisol, thereby increasing perceived pain. Chronic pain induces a chronic increase in cortisol and other central mediators of the HPA axis. Cortisol is one of the physiological indices used to quantify stress, with salivary cortisol levels reflecting HPA axis activity and quantifiable non-invasively through saliva samples using ELISA methods. Currently, physiological stress assessment is easily performed by measuring cortisol levels in saliva samples.