Is there a difference in the analgesic response to intra-articular bupivacaine injection in people with knee osteoarthritis pain with or without central sensitisation? Protocol of a feasibility randomised controlled trial

INTRODUCTION: Pain is the main symptom of osteoarthritis (OA) with approximately 50% of patients reporting moderate-to-severe pain. Total knee replacement (TKR) is the ultimate treatment option to alleviate pain in knee OA. Nevertheless, TKR does not provide complete relief for all as approximately 20% of patients experience chronic postoperative pain. Painful peripheral stimuli may alter the central nociceptive pathways leading to central sensitisation that can influence treatment response in patients with OA. Currently, there is no objective protocol for detecting whether a patient will respond to a given treatment. Therefore, there is a need for a better mechanistic understanding of individual factors affecting pain relief, consequently informing personalised treatment guidelines. The purpose of this research is to examine the feasibility of conducting a full-scale mechanistic clinical trial in painful knee OA investigating the analgesic response to intra-articular bupivacaine between those with or without evidence of central sensitisation. METHODS AND ANALYSIS: The Understanding Pain mechanisms in KNEE osteoarthritis (UP-KNEE) study is a feasibility, double-blinded, placebo-controlled randomised parallel study in participants with radiographically defined knee OA and with self-reported chronic knee pain. The study involves the following assessments: (1) a suite of psychometric questionnaires; (2) quantitative sensory testing; (3) magnetic resonance imaging (MRI) scan of the knee and brain; (4) a 6-minute walk test; and (5) an intra-articular injection of bupivacaine or placebo (sodium chloride 0.9%) into the index knee. Assessments will be repeated post intra-articular injection apart from the MRI scan of the knee. Our aim is to provide proof of concept and descriptive statistics to power a future mechanistic trial. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Health Research Authority (HRA) (REC: 20/EM/0287). Results will be disseminated via peer-reviewed journals and scientific conferences. The results will also be shared with lay audiences through relevant channels, such as Pain Centre Versus Arthritis website and patient advocacy groups. TRIAL REGISTRATION NUMBER: NCT05561010.