Breast cancer is the most common diagnosed malignancy among females and the 5th cause of
cancer-related deaths with an estimated number of 2.3 million new cases and 685,000
deaths worldwide in 2020.
Different modalities are used for management of breast cancer including surgery,
radiation therapy (RT), chemotherapy (CT), endocrine (hormone) therapy (ET), and targeted
therapy. Modified Radical Mastectomy (MRM) is one of the main modalities of breast cancer
treatment. It accounts for 31% of all breast surgeries. It has been reported that 40% of
the females complain from moderate-to-severe pain in the immediate post-operative period
after breast cancer surgery.
Acute post-mastectomy pain can cause adverse impacts on the patients as delayed discharge
from post-operative recovery area, impairs pulmonary and immune functions, increases risk
of ileus, thromboembolism, myocardial infarction and may lead to increased length of
hospital stay. It is also an important factor leading to the development of chronic post
mastectomy pain syndrome (PMPS) in almost half of the patients.
The International Association for the Study of Pain (IASP) defines PMPS as pain which
persists more than 3 months after mastectomy that affects the anterior thorax, axilla,
and/or medial upper arm. It is usually described as the feeling of burning, stabbing, and
pulling around the treatment side. The underlying pathophysiology of PMPS is highly
complicated and involves both peripheral and central sensitization. It results from
injury to the peripheral nerves in the axilla or the chest wall during the dissection of
axillary lymph nodes. Multiple risk factors are involved in the development of PMPS
including acute postoperative pain, age < 40 years, increased BMI , diagnosis at
later-stage disease, psychosocial factors (i.e., anxiety, depression, sleep disturbances,
catastrophizing), preoperative pain and adjuvant therapy (chemotherapy, radiation
therapy).(8)Because PMP involves issues associated not only with pain management, but
also with psychosocial disruption, the assessment of each of these domains should be
addressed routinely so as to enable early detection and treatment.
Different pharmacological tools have been in use for either prevention or treatment of
such refractory pain syndrome with variable efficacy.
Tianeptine is a unique antidepressant and anxiolytic medication that stimulates the
uptake of serotonin (5-hydroxytryptamine; 5-HT), and 5-hydroxyindoleacetic acid (5-HIAA)
in brain tissue . It acts as a full agonist at the mu-type opioid receptor (MOR) , the
serotonin receptor ,dopamine (D2/3) receptors and glutamate receptors .It also reduces
the hypothalamic-pituitary-adrenal response to stress, and thus prevents stress-related
behavioral issues.
Pregabalin is a new synthetic molecule and a structural derivative of the inhibitory
neurotransmitter γ-aminobutyric acid. It is an α2-δ (α2-δ) ligand that has analgesic,
anticonvulsant, anxiolytic, and sleep-modulating activities. Pregabalin binds potently to
the α2-δ subunit of calcium channels, resulting in a reduction in the release of several
neurotransmitters, including glutamate, noradrenaline, serotonin, dopamine, and substance
P , Pregabalin has also been found to be effective at reducing acute postoperative pain
The efficacy of pregabalin in treating acute postsurgical pain has been demonstrated in
numerous studies. A recent meta-analysis has suggested that pregabalin, at all doses and
administration regimens, has opioid-sparing effects and reduces pain scores in the
postsurgical setting, at the expense of increased sedation and visual disturbances;
however, the efficacy of pregabalin in providing such in various surgical categories
remains uncertain, and it is not known whether the risk: benefit ratio is greater for
certain surgical categories The aim of this study is to assess the efficacy of the
perioperative use of Pregabalin versus Tianeptine on the emergence of PMPS in female
patients undergoing MRM for breast cancer.