Lymphocyte opioid receptors as innovative biomarkers for osteoarthritic chronic pain: study protocol for the assessment and risk management of opioid tailored therapy, before hip surgery, to prevent chronic pain and opioids tolerance/addiction development

INTERVENTION: 60 patients undergoing hip surgery will be enrolled in a randomized phase IV study. Patients will be randomised in a double‐blind manner into three medication arms administered in common practice. Randomisation will be performed using a computational approach, based on a single sequence of random assignments (simple randomization). Patients and their medical doctors will be blind to the assigned treatment. Each arm involves 20 patients: 1. Tapentadol 25mg x 2 die 2. Tapentadol 75mg x 2 die 3. NSAIDs/paracetamol in accordance with surgeon’s custom All the arms will follow the specific pharmacological plan for 30 days before surgery and 15 days after (if the patient feels pain). Each patient will be subjected to five blood sample collections at precise time points: the day of enrolment and starting therapy (T0); the 30th day of therapy, coinciding with the moment of surgery (T2); the day after surgery (T3); 30 days after surgery (T4); 60 days after surgery, in correspondence with the final assessment and follow up (T5). T1 coincides with clinical examination, 15 days after the enrolment, without any blood collection. On the day of surgery, patients will be monitored with standard practices, such as electrocardiogram, oxygen saturation, invasive and non‐invasive blood pressure monitoring. They will attend a physical examination, concerning Harris Hip Score for evaluation of hip movement, stability, strength, presence of any deformities, joint and functional limitations; radiographs of the axial pelvis and in anteroposterior, to determine the extent of the degree of arthritis or necrosis; pain assessment will be done using the model inside the Harris Hip Score, by adding evaluations of pain intensity (NRI scale) during orthostatic and clinostat posture. During the surgery, a bone marrow sample will be collected. Bone marrow biopsy will be fixed for 24h in buffered 4% formalin and included in paraffin. 3µm sections will be used for bone marrow morphological and morp CONDITION: Total hip arthroplasty for osteoarthritis or aseptic necrosis of the femoral head ; Surgery PRIMARY OUTCOME: 1. Expression and functional characteristics of opioid receptors on the lymphocyte surface, measured using peripheral blood analysis (Immunophenotype analysis, Q‐PCR, western blotting, ELISA) at T0, T2, T3, T4 and T5; 2. Bone marrow morphological and morphometric evaluation, using bone marrow biopsy, hematoxylin/eosin staining protocol and cellular immune‐phenotypic typization at T2 SECONDARY OUTCOME: 1. Hip movement, stability, strength, presence of any deformities, joint and functional limitations, evaluated using the Harris Hip Score at T0, T1, T2, T4, T5; 2. Degree of arthritis/necrosis, measured using axial and anteroposterior pelvic radiographs at T0; 3. Pain intensity, measured using the NRI scale at T0, T1,T2, T3, T4, T5; 4. Electrocardiogram, oxygen saturation, invasive and non‐invasive blood pressure monitoring at T2; 5. Side effects evaluation (tolerance or addiction) at T2, T4, T5 INCLUSION CRITERIA: 1. Patients who started opioid analgesics category and will undergo total hip arthroplasty for osteoarthritis or aseptic necrosis of the femoral head 2. Patients who started NonSteroidal Anti‐Inflammatory Drugs (NSAIDs) and will undergo total hip arthroplasty (THA) for osteoarthritis or aseptic necrosis of the femoral head 3. Males and female adults (from 18 years old)