Background & Aims

Osteoarthritis (OA) is a common chronic pain (CP) syndrome (1). OA-associated CP might lead to joint replacement, but 20% of patients still experience CP after total knee arthroplasty (TKA, 2). Post-surgery pain could be due to factors like infection, surgical procedures, and psychosocial elements. Excluding these, a significant minority continues to feel pain. Recent studies suggest immune and nervous system interactions contribute to OA-associated CP. Recently, we identified Mu+ B cells percentage of expression, named Mu-Lympho-Marker (MLM), as potential biomarkers for objective CP diagnosis in OA and fibromyalgia patients (3, 4). Low percentage of Mu+ B cells in CP patients might indicate reduced opioid receptor reserve for pain inhibition by immune cells. Here we explore the role of MLM as a diagnostic biomarker for pain chronicization in patients with end-stage TKA who have failed nonsurgical management aiding in tailored rehabilitation, and recovery.

Methods

This is an on-going observational, longitudinal study including patients with end-stage TKA patients (Pz) who have failed nonsurgical management and pain-free subjects (Ctrl). Blood samples are collected to analyze Mu+ B cells percentage of expression through flow citometry, using Mu opioid receptor antibody. Pain assessment is performed to correlate pain severity with Mu expression in B cells. The following scales are used 1) 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 (I-KOOS).

Results

Following the assessment of inclusion and exclusion criteria, clinical data were collected in a special Case Report Form (CRF), which included demographics, clinical characteristics, and pharmacological history. Prior to participation, all patients were on their own personal pharmaceutical therapy. The participants to the study ranked between 60 and 75 years old, mean age 68±5.7. Patients’ pain intensity ranked between moderate (4-6) to severe (7-10) pain. We analyzed the blood samples of all enrolled patients to detect the expression of Mu receptors on the membrane of B lymphocytes. Flow cytometry results showed intra-group homogeneity and the percentage of Mu+ B cells was statistically lower in Pz than in ctrl subjects. We found intra-group homogeneity (Pz mean: 7.12 ± 1.25; Ctrl mean: 40.70 ± 2.5) and significant differences of Mu expression between Pz and Ctrl (p < 0.001). Pz declaring moderate and severe pain showed insignificant differences in percentage of Mu+ B cells.

Conclusions

The finding of a biomarker capable of predicting the probability of chronic pain following TKA could be extremely beneficial in guiding the creation of personalized care for specific patient groups, enhancing treatment outcomes, and avoiding unnecessary suffering and expenses. Here, we found that patients with end-stage TKA who have failed nonsurgical management present a significantly lower percentage of Mu+ B cells compared to the negative control group. We also analyzed these data considering the intensity of the pain and found, for the first time, that TKA patients with moderate/severe intensity of pain on the NRS presented a lower percentage of B cells expressing Mu opioid receptor than patients in pain-free control group. The MLM characterization as a specific biomarker, easily monitored in a blood sample and associated with a specific pain profile, holds a great promise for both the assessment and the management of TKA patients, thus paving the way to individualized rehabilitati

References

1.Fu K et al. Rheumatology (Oxford). 2018
2. Wylde V et al. EFORT Open Rev. 2018
3. Raffaeli W et al. Int J Mol Sci. 2020
4. Malafoglia V et al. Neuroscientist. 2021

Ackowlwdgement:

Finanziato dall’Unione europea – Next Generation EU- PRIN 2022 Prot. 202273HF83

GR-2021-12375174

AIDED BY A GRANT FROM THE INTERNATIONAL SOCIETY OF ARTHROSCOPY, KNEE SURGERY AND ORTHOPAEDIC SPORTS MEDICINE AND THE ORTHOPAEDIC RESEARCH AND EDUCATION FOUNDATION

Presenting Author

Sara Ilari

Poster Authors

Sara Ilari

PhD

IRCCS San Raffaele

Lead Author

Valentina Malafoglia

IRCCS SAN RAFFAELE- Rome

Lead Author

Filippo Familiari

Department of Orthopedic and Trauma Surgery, "Magna Græcia" University, "Mater Domini" University Ho

Lead Author

Michael Tenti

Institute for Research on Pain, ISAL Foundation, Rimini, Italy.

Lead Author

Lucia Carmela Passacatini

IRCCS San Raffaele

Lead Author

Roberta Macrì

University Magna Graecia of Catanzaro

Lead Author

Saverio Nucera

University Magna Graecia- CZ

Lead Author

Vincenzo Mollace

Pharmacology Laboratory, Institute of Research for Food Safety and Health IRC-FSH, Department of Hea

Lead Author

Olimpio Galasso

Lead Author

Giorgio Gasparini

Department of Orthopedic and Trauma Surgery, "Magna Græcia" University, "Mater Domini" University Ho

Lead Author

William Raffaeli

Fondazione ISAL, Institute for Research on Pain

Lead Author

Carolina Muscoli

Department of Health Sciences; University "Magna Graecia" of Catanzaro, Institute of Research for F

Lead Author

Topics

  • Assessment and Diagnosis