Physical Exercise, Motor Activity and Depression in Post-mastectomy Pain Syndrome

Chronic pain is one of the most frequent occurring after surgery. It leads 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, or persistent post-surgical pain (PPSP), was later proposed by Werner and Kongsgaard in 2014. The proposed definition was "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)".

Persistent post-mastectomy pain (PPMP) is a major individual and public health problem. The etiology of persistent pain after mastectomy is still unclear, although it is likely multifactorial and may be partially of neuropathic origin. While surgical factors, including more extensive surgery (total vs partial mastectomy), axillary lymph node dissection, and reconstruction, have been postulated to serve as important risk factors for chronic pain, many studies do not support this association. Adjuvant treatment, such as radiation, chemotherapy, and hormone therapy, has also been occasionally associated with persistent pain.It is estimated that 25-60% of patients who have undergone breast cancer removal surgery suffer from PMP syndrome and psychosocial factors such as anxiety, depression, sleep disturbance and catastrophizing have proven to be important contributors to the development of persistent pain . A link between pain and depression is well known, it is suggested that 30%-45% of patients affected by chronic pain, experience depression. Several studies have suggested a bidirectional relationship between depression and pain, suggesting that depression is a positive predictor of the development of chronic pain and chronic pain can increases the risk of developing depression. Moreover depression is considered a moderator of the relationship between pain severity and physical functioning . It is known that depressive disorders overlap with anxiety disorders, anxiety symptoms are included in the diagnostic criteria for major depressive disorder in the diagnostic and statistical manual of mental disorders 5th edition (DSM-5). Results obtained from from case control studies suggest that inflammation could be involved in generalized anxiety disorder, indicating that inflammation could increase subsequent to the development of an anxiety disorder.

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 depression and anxiety 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 depression, was used the Beck's Depression Inventory (BDI) and for the anxiety evaluation, will be administered the Generalized Anxiety Disorders-7 (GAD-7). 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 time-points (12 and 24 weeks after surgery) biomarkers of pain, inflammation and correlated to anxiety and depression will be measured together with routine blood parameters. Specifically, the following biomarkers will be evaluated: IL-17, IL-1beta, brain-derived neutrophic factor (BDNF), cortisol and adrenocorticotropic hormone (ACTH).

Inclusion criteria

over the age of 18 with a diagnosis of previous Stages I-III breast cancer

Exclusion criteria

• medical history of other types of cancer;
• disease related to the immune system (e.g. multiple sclerosis, HIV, lupus);
• recent symptoms of illness (cough, fever);
• no antinflammatory or antidepressive or anxiolitic drugs assumption during the first six months after surgery
• waiting breast reconstruction;
• not chemotherapy or radiation during the first six months after surgery: