Understanding Pain Mechanisms in Knee Osteoarthritis
Research type
Research Study
Full title
Is there a difference in the analgesic response to intra-articular bupivacaine injection in people with knee osteoarthritis pain with or without central sensitisation?: a feasibility randomised controlled trial
IRAS ID
270642
Contact name
Brigitte Scammell
Contact email
Sponsor organisation
Nottingham University Hospitals NHS Trust
Duration of Study in the UK
1 years, 2 months, 31 days
Research summary
Understanding pain mechanisms in knee osteoarthritis
Osteoarthritis (OA) is a leading cause of disability worldwide. Approximately 20% of adults aged over 45 years in England are diagnosed with knee OA. Pain is the defining symptom which has a substantial impact on quality of life. Nearly 100,000 total knee replacement (TKR) operations are performed annually in UK. One of the principal aims of performing TKR is to alleviate pain. Nevertheless, persistent postoperative pain is reported by more than 20% of patients.
Knee pain severity often differs between patients who have the same degree of joint damage. This suggests that other factors influence the pain severity experienced by the patient. Amongst these factors is the alteration in pain processing by the brain, known as central sensitization. Although there are a few potential tools to measure central sensitization, there is no easy test that can confirm it.
Therefore, there is a need to investigate how knee OA pain is processed to help shape novel treatment plans. In this feasibility randomised controlled trial, we propose to explore the links between knee pain and the brain in knee OA patients with self-reported chronic knee pain in preparation for a future definitive trial. We will use brain and knee MRI scans, and other experimental approaches. This will offer a step forward in the knowledge of chronic pain in knee OA which may enable individualised treatment strategies. This study will be carried out at the Sir Peter Mansfield Imaging Centre, University of Nottingham.
Summary of Results
Lay Summary The UP-KNEE study was a single-centre feasibility study based at the University of Nottingham and Nottingham University Hospitals. The study aimed to investigate why some people with knee osteoarthritis experience pain differently from others and whether pain may be driven by different underlying mechanisms.
Participants awaiting knee replacement surgery were invited to attend a single research visit. During this visit they completed questionnaires about their pain, underwent walking assessments, quantitative sensory testing (QST), and MRI scans of the knee and brain. Participants were randomly allocated to receive either a local anaesthetic (bupivacaine) injection or a saline injection into the knee joint. The study aimed to explore whether response to the injection was associated with findings from MRI scans, questionnaires and sensory testing. An important objective of the study was also to determine whether a larger future trial would be practical and acceptable to participants.
The study experienced significant delays during set-up and delivery. These were largely related to disruption caused by the COVID-19 pandemic, which affected research activity across the NHS and delayed study opening and recruitment. These delays had knock-on effects on project timelines, funding and staffing.
Recruitment proved challenging. Between November 2023 and May 2024, 516 patients on knee replacement waiting lists were screened. Of these, 176 met the eligibility criteria and were invited to participate. Nineteen patients expressed an interest in taking part and ten participants were ultimately recruited, seven completed the study. The inclusion and exclusion criteria were not a major barrier to participation. However, many patients were concerned that participation might delay their planned surgery because of the required interval between injection and operation. Other barriers included the length of the research visit and ongoing concerns about attending hospital following the COVID-19 pandemic.
Although the planned recruitment target was not achieved, the study demonstrated that the research procedures, including questionnaires, sensory testing, MRI scanning and knee injections, were acceptable to participants who enrolled. The study also identified important practical challenges that would need to be addressed before undertaking a larger trial. In particular, future studies may benefit from recruitment through primary care and from additional trial management support to improve study delivery.
Overall, the study provided valuable information about the feasibility of this research approach and helped inform the design of future studies investigating personalised approaches to pain management in people with knee osteoarthritisREC name
East Midlands - Nottingham 1 Research Ethics Committee
REC reference
20/EM/0287
Date of REC Opinion
27 Jan 2021
REC opinion
Further Information Favourable Opinion