Understanding Pain Mechanisms in Knee Osteoarthritis

UP-KNEE study is a feasibility, double-blind, placebo-controlled randomised parallel study in participants with radiographically defined knee OA, and with self-reported chronic knee pain.

Osteoarthritis (OA) of the knee joint is a common cause of chronic pain, disability and impaired quality of life. Knee OA affects \~ 1 in 5 adults over 45 years, with many requiring major knee surgery to alleviate pain and restore mobility. However, \> 1 in 5 patients will continue to suffer from pain despite surgery. It remains largely unknown who will fail to respond, and why.

Chronic postoperative pain may be linked to a particular type of pain, that is not only driven by the joint damage itself but by changes in the central nervous system (central pain). Several lines of evidence support this idea, but there is a need for a better understanding of the underlying mechanisms as well as a better tool to differentiate between peripherally- and centrally-augmented knee pain in order to identify who will benefit the most from knee surgery.

To this end, the proposed research is a feasibility study aiming to provide proof of concept for a future main trial. The study combines the diagnostic power of non-invasive imaging with experimental approaches to investigate central pain by modelling the peripheral effects of knee surgery. This will provide novel insights into the contribution of peripheral and central pain mechanisms in knee OA which can pave the way for better treatment results.

This study is expected to last for one year. It is funded by Versus Arthritis Pain Centre and forms part of a wider scientific project aiming at increasing knowledge and understanding of OA pain.

Eligibility Criteria:
Inclusion Criteria:

* Radiographically defined OA knee changes (K/L \> 2);
* Must have self-reported knee pain (measuring at least 30 mm to 80 mm on a 100 mm VAS for rest, use or night pain);
* Able to give informed consent;
* Aged 45 years and older;
* All genders;
* Able to perform the six-minute walk test.

Exclusion Criteria:

* Aged less than 45 years;
* Breastfeeding or pregnancy;
* Not having the capacity to consent;
* Non-English speakers;
* Major medical, neurological and psychiatric co-morbidities;
* Hip OA (ipsilateral or contralateral);
* Fibromyalgia;
* Sensory dysfunctional illness;
* Chronic pain conditions other than OA;
* Presence of local or systemic infection or suspicion of infection in the knee joint, overlying soft tissue or elsewhere;
* History of septic arthritis in the knee to be injected;
* Acute haemarthrosis in the joint to be injected;
* Recent trauma within 72 hours;
* Prosthetic joint;
* Presence of broken skin or rash over the area to be injected;
* Severe coagulopathy (can take aspirin or anti-platelets inhibitors such as clopidogrel);
* Any anti-coagulant therapy (e.g. warfarin);
* Severe liver disease or severe kidney disease;
* Known hypersensitivity, allergy or intolerance to local anaesthetic / bupivacaine;
* Recently taken other medicines containing local anaesthetic / bupivacaine within 1 month;
* Surgery planned within 3 months of entry to study;
* Neuropathic pain medications such as opioid analgesics, antiepileptic drugs such as pregabalin / gabapentin, and tricyclic antidepressants such as amitriptyline when taken for neuropathic pain treatment;
* Current or recent intake centrally-active medication (e.g. have recently taken monoamine oxidase inhibitor (MAOI));
* Complete heart block;
* The presence of any contraindication for MRI.