Persistent Pain in Pharmacologically or Surgical Treated Osteoarthritis: Role of Mu-Limpho Marker

The goal of this prospective observational study is to analyze the percentage of expression of B and NK cells expressing Mu opioid receptor on their surface, named Mu-Lympho-Marker (MLM), to measure pain progression in Osteoarthritis patients and its association with specific rehabilitation programs. In particular, we want to analyze the role of MLM as diagnostic biomarker of pain chronicization. The main aims are: * to explore the relationship between Mu+ B and NK cells percentage and pain progression in OA patients, also investigating whether this characteristic is associated to particular outcome of pharmacological and/or surgery interventions and rehabilitation * to characterize Mu+ B and NK cells in terms of maturation states, activation/inhibition and functional properties, as well as their ability to respond to Mu stimulation, in order to understand whether these cells can have a role in the pathogenesis of OA associated CP * to investigate the potential confounding effect of other biological and psychological elements in the relationship between the MLM and OA pain progression Researchers will compare two study groups: 1. Experimental group: subjects suffering from symptomatic knee OA. 1S)surgical subgroup: OA patients from the experimental group requiring primary TKA due to the failure of conservative treatment, thus undergoing surgical intervention; 2. Control group: subjects without any chronic pain, undergoing occupational health surveillance matched by age, sex and psychological profile with the experimental group patients Participants will be asked to do blood sample collections at specific time points to evaluate MLM stability over time and its modulation according to pharmacological/surgical and rehabilitation interventions. Subjects in the control group will undergo 2 blood sample collections. Pain assessment will be performed at all scheduled time points to correlate pain severity with Mu expression in B and NK cells.

All patients will undergo the blood sampling at the day of the enrollment (T0), at 1 month (T1), 3 months (T2) and 6 months(T3) after the enrollment. The subgroup of patients requiring primary TKA will undergo blood sampling the day of the surgical intervention (T1-S), the 5th day (T2-S), and the 90th day after the intervention (T3-S). Pain-free subjects will undergo blood sampling the day of the enrollment (T0) and 6 months (T3) later. Participants will be asked to self-fill the 11-point numerical rating scale (NRS) test, where 0= No pain and 10= worst possible pain, 2) the Italian version of the Brief Pain Inventory and the Italian version of the Neuropathic Pain Symptom Inventory NPSI (I-NPSI), 3) the Italian version of the Knee injury and Osteoarthritis Outcome Score (KOOS).