Beyond Synovitis: Molecular and Neuroimmune Mechanisms Informing Target-Joint Attribution and Pain Phenotyping for Arthroplasty in Inflammatory Arthritis.
12 affiliations
- 1Institute of Medical Science, The John Paul II Catholic University of Lublin, 20-708 Lublin, Poland.
- 2Clinical Department of Rheumatology, Provincial Integrated Hospital in Plock, 09-400 Plock, Poland.
- 3Collegium Medicum, The Mazovian Academy in Plock, 09-402 Plock, Poland.
- 4Clinical Department of Trauma and Orthopedic Surgery, The John Paul II Catholic University of Lublin, 21-300 Radzyn Podlaski, Poland.
- 5Department of Trauma and Orthopedic Surgery, Ruda Slaska City Hospital, 41-793 Ruda Slaska, Poland.
- 6Henry JN Taub Department of Emergency Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
- 7Department of Geriatrics, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland.
- 8Rheumatology Unit, ViaMed Ursus Medical Center, 02-495 Warsaw, Poland.
- 9Department of Rheumatology, Silesian Center for Rheumatology, 43-450 Ustron, Poland.
- 10Institute of Biological Science, The John Paul II Catholic University of Lublin, 20-950 Lublin, Poland.
- 11Department of Trauma and Orthopedic Surgery, Silesian Center for Rheumatology, 43-450 Ustron, Poland.
- 12Clinical Department of Orthopedics, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 41-800 Katowice, Poland.
Abstract
Arthroplasty can provide substantial pain and functional improvement in inflammatory arthritis, but structural indications alone do not determine how much of a patient's overall symptom burden will respond to surgery. Persistent or widespread pain may reflect active inflammation, irreversible joint damage, neuropathic or extra-articular generators, and distributed pain amplification, which we use as a descriptive term for pain extending beyond the target joint and influenced by broader sensory, symptomatic, and contextual processes. This critical structured narrative review integrates direct inflammatory-arthritis arthroplasty evidence, disease-specific pain-phenotyping studies, indirect osteoarthritis perioperative data, and molecular and mechanistic literature. We link cytokine/prostaglandin signalling, neurotrophin- and ion-channel-mediated nociceptor sensitisation, immunosensory signalling, and spinal neuron-glia plasticity to peripheral and central nociceptive amplification. We then propose the Target-Joint Attribution and Pain-Amplification Framework, comprising four provisional clinical phenotypes (A-D): structural-concordant, inflammation-dominant, mixed target-joint/distributed pain-amplification, and distributed pain-dominant. Questionnaire or sensory-test thresholds do not establish mechanisms or surgical eligibility. The framework translates these molecular and neuroimmune mechanisms into testable hypotheses for perioperative phenotyping, biomarker validation, and interpretation of postoperative pain trajectories. Direct phenotype-specific evidence in inflammatory-arthritis arthroplasty remains sparse; prospective validation integrating joint-specific outcomes with molecular and sensory measures is required.
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BibTeX
@article{pruc2026beyond,
title = {{Beyond Synovitis: Molecular and Neuroimmune Mechanisms Informing Target-Joint Attribution and Pain Phenotyping for Arthroplasty in Inflammatory Arthritis.}},
author = {Michal Pruc and Andrzej Bielski and Robert Weglowski and Jaroslaw Pecold and Lukasz Szarpak and Iwona Jannasz and Monika Olczak-Pruc and Maciej Lewicki and Maciej Maslyk and Mahdi Al-Jeabory},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198551},
url = {https://europepmc.org/article/MED/42883797},
note = {CC BY},
}
RIS
TY - JOUR
TI - Beyond Synovitis: Molecular and Neuroimmune Mechanisms Informing Target-Joint Attribution and Pain Phenotyping for Arthroplasty in Inflammatory Arthritis.
AU - Michal Pruc
AU - Andrzej Bielski
AU - Robert Weglowski
AU - Jaroslaw Pecold
AU - Lukasz Szarpak
AU - Iwona Jannasz
AU - Monika Olczak-Pruc
AU - Maciej Lewicki
AU - Maciej Maslyk
AU - Mahdi Al-Jeabory
PY - 2026
DA - 2026/09/24
JO - International journal of molecular sciences
DO - 10.3390/ijms27198551
UR - https://europepmc.org/article/MED/42883797
AB - Arthroplasty can provide substantial pain and functional improvement in inflammatory arthritis, but structural indications alone do not determine how much of a patient's overall symptom burden will respond to surgery. Persistent or widespread pain may reflect active inflammation, irreversible joint damage, neuropathic or extra-articular generators, and distributed pain amplification, which we use as a descriptive term for pain extending beyond the target joint and influenced by broader sensory, symptomatic, and contextual processes. This critical structured narrative review integrates direct inflammatory-arthritis arthroplasty evidence, disease-specific pain-phenotyping studies, indirect osteoarthritis perioperative data, and molecular and mechanistic literature. We link cytokine/prostaglandin signalling, neurotrophin- and ion-channel-mediated nociceptor sensitisation, immunosensory signalling, and spinal neuron-glia plasticity to peripheral and central nociceptive amplification. We then propose the Target-Joint Attribution and Pain-Amplification Framework, comprising four provisional clinical phenotypes (A-D): structural-concordant, inflammation-dominant, mixed target-joint/distributed pain-amplification, and distributed pain-dominant. Questionnaire or sensory-test thresholds do not establish mechanisms or surgical eligibility. The framework translates these molecular and neuroimmune mechanisms into testable hypotheses for perioperative phenotyping, biomarker validation, and interpretation of postoperative pain trajectories. Direct phenotype-specific evidence in inflammatory-arthritis arthroplasty remains sparse; prospective validation integrating joint-specific outcomes with molecular and sensory measures is required.
SN - 1422-0067
ER -