Physical Exercise, Motor Activity on Sleep Disorders in Post-Mastectomy Pain Syndrome

Chronicization of pain is frequently occurring after surgery, thus leading often to functional limitations and psychological disorders, with a negative impact on quality of life.

Chronic post-surgical pain (CPSP) was first defined as "pain that develops after surgical intervention and lasts at least 2 months; other causes of pain have to be excluded, in particular, pain from a condition existing before the surgery". An updated definition of CPSP, was later proposed as "pain persisting at least three months after surgery, that was not present before surgery, or that had different characteristics or increased intensity from preoperative pain, localized to the surgical site or a referred area, and other possible causes of the pain were excluded (e.g., cancer recurrence, infection)".

Chronic pain following mastectomy, referred to at that time as intercostobrachial nerve entrapment syndrome, was first identified in a case series of patients who underwent mastectomy in the 1970s. This condition is now referred to as post-mastectomy pain syndrome (PMPS). The International Association for the Study of Pain (IASP) defines PMPS as persistent, neuropathic pain that develops soon after mastectomy or lumpectomy located in the anterior surface of the chest axilla, shoulder, or upper half of the arm.

The etiology of persistent pain after mastectomy is still unclear, because of its possible multifactoriality with a partial neuropathic origin. While surgical factors, including axillary lymph node dissection, and reconstruction, have been postulated to serve as important risk factors for chronic pain, many studies do not fully support this association. Adjuvant treatment, such as radiation, chemotherapy, and hormone therapy, has also been occasionally associated with persistent pain consequent to mastectomy.

Psychosocial factors such as anxiety, catastrophizing and sleep disorders are being revealed as crucial contributors to individual differences in pain processing and outcomes. There is substantial evidence supporting the association between chronic pain and sleep, as constant pain affects wakefulness and, consequently, sleep quality. Hence, there is a close relationship between chronic pain and insomnia, and sustained sleep restriction further diminishes emotional and physical well-being, leading to depression, chronic fatigue and anxiety in many patients.

Sleep disturbances have been found to both contribute to and result from immune-neuro-endocrine disorders, which are also associated with the presence of chronic pain in general.

Sleep disturbances encompass both sleep quality and disorders. Sleep quality refers to a multifactorial process encompassing both sleep duration and depth. Sleep disorders are conditions that involve both subjective and objective symptoms, such as insomnia disorders, sleep-related breathing disorders, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, sleep-related movement disorders, parasomnias, and other sleep disorders.

Humans physiological circadian rhythms is closely associated with sleep quality. The hormones cortisol and melatonin and core body temperature show notable circadian rhythms. Core body temperature decreases at night and increases during daytime. Cortisol and melatonin are counter-regulatory hormones; melatonin levels increase at night, when cortisol levels decrease to their lowest point, and cortisol levels increase to their highest point in the morning, when melatonin levels decrease to their lowest. Abnormal melatonin and cortisol rhythms can cause sleep problems.

Cortisol, a prominent hormone in circadian rhythms, reacts rapidly to exercise, stimulating the sympathetic nervous system as its concentration rapidly increases. Kanaley et al. reported that evening exercise significantly increased cortisol concentrations compared to morning exercise. Additionally, cortisol concentration significantly increases after moderate-intensity exercise compared with low-intensity exercise.

Current evidence indicates that sleep disorders may contribute to the growing health burden in modern societies. Insufficient and poor-quality sleep represent high-risk factors for health outcomes such as cardiovascular disease, cognitive impairment, and metabolic dysfunction; poor sleep has also been associated with risk-taking behavior, accidents, increased mortality rates, and diminished quality of life.

It is well documented that physical activity can improve sleep quality in a variety of ways, increasing the production of melatonin, a hormone that regulates sleep-wake cycles, moreover, several studies suggest that physical activity improves sleep disorders by a modulation of cortisol level and an increase of melatonin levels. Cortisol reacts rapidly to exercise, stimulating the sympathetic nervous system as its concentration rapidly increases. Some studies report that evening exercise significantly increased cortisol concentrations compared to morning exercise. Additionally, cortisol concentration significantly increases after moderate-intensity exercise compared with low-intensity exercise.

As a result, physical activity can assist in falling asleep faster and sleeping better. Second, physical activity reduces stress, which is a typical impediment to falling and staying asleep. Third, physical activity improves mood, leading to increased enthusiasm for physical exercise and a positive feedback loop. It was shown that active people had higher levels of positive affect and tranquility during exercise and lower levels of negative affect and tiredness. Finally, physical activity helps to regulate body temperature, which is necessary for falling asleep, as an increase in body temperature during physical activity aids the eventual drop 30-90 minutes post-exercises, facilitating easier sleepiness.

On the light of the above considerations, the aim of this study was to evaluate the effects of physical activity on the intensity and interference of chronic pain in daily activities and the effect on sleep disturbance in patient underwent mastectomy.

Study population: women underwent unilateral or bilateral mastectomy due to resection of stage II and III breast cancer not followed by breast reconstruction aged 18 years or older who have not received chemotherapy or radiation. Pain assessment: Pain assessment is a multidimensional process, which must take into account all the components of suffering, both physically, psychologically and socially. The assessment of pain and motor activity of each participant in the study will be carried out 3 and 6 months after surgery. Pain will be assessed by administration of Numerical Rating Scale (NRS) questionnaire. For the evaluation of sleep disorders, will be administered the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI). All the evaluation will be performed 3 and 6 months after surgery. The IPAQ (International Physical Activity Questionnaire) questionnaire measures the type and amount of physical activity that is normally done.

The questions refer to the activity carried out in the last 7 days. It will be administered at 3 and 6 months after surgery.The expected duration of the study can be considered to be approximately 12 months. At the same timepoints (12 and 24 weeks after surgery) hematic biomarkers correlated to pain, and sleep disorders will be measured together with routine blood parameters. Specifically, the following biomarkers will be evaluated: cortisol, adrenocorticotropic hormone (ACTH) and melatonin.