Short summary

Pain is the principal symptom in knee osteoarthritis (OA) and has major implication worldwide.  Current treatment options have only moderate effects and often patients experience persistent pain or side-effects. Novel advances in the field of cryoneurolysis applies low temperatures to disrupt nerve signaling at the painful area, providing pain relief. The current project aims to determine the safety and effectiveness of cryoneurolysis in its ability to decrease pain in patients with knee OA. Cryoneurolysis could potentially provide an effective, safe and non-pharmacological therapeutic option to treat pain in OA patients, and improve the outcomes of existing treatment options such as exercise.

Rationale

Chronic pain represents a major challenge worldwide, with significant clinical, social and economic implications. In Denmark and the rest of Europe, 20% of all chronic pain conditions is related to osteoarthritis (OA). There are over 300.000 people diagnosed with OA in Denmark alone. Projections show that the incidence of this pathology will increase significantly. The pain and loss of function associated with OA, results in a considerable amount of years lived with disability and has significant socioeconomic consequences, estimated at 1 - 2.5% of the gross domestic product in western countries. Knee OA in particular, has a high prevalence rate compared to other types of OA, and is also present in the younger working age population.The treatment of knee OA typically focuses on pain relief, however the effects of current conservative treatment options remain small to moderate and most are associated with side effects. In many cases patients alternatively may be subjected to partial/total knee arthroplasty 

(TKA). TKA is considered to be an effective treatment for end-stage knee osteoarthritis however more than 20% of patients receiving TKA, experience persistent and unchanged pain post-surgery. Reviewing these results, focus should be on low-risk, minimally invasive therapies. Novel advances in the field of cryoneurolysis are in that respect promising. Cryoneurolysis has made it possible to apply low temperatures [-20°C ; -100°C] to a target percutaneous peripheral nerve, causing Wallerian degeneration. This disrupts nerve function while structural elements of the nerve bundle remain intact allowing for complete regeneration and functional recovery of the nerve over time. Cryoneurolysis on peripheral nerves has been shown to provide pain relief in a variety of chronic pain conditions such as lumbar facet joint pain, plantar fasciitis, occipital neuralgia, post thoracotomy pain syndrome, and Morton's neuroma. The ability to target the genicular nerves to reduce pain around the knee has been reported by studies applying radio frequency ablation (RF) but cryoneurolysis has in that respect been associated with less adverse effects. Recently, Radnovich, et al. targeted the infrapatellar branch of the saphenous nerve (ISN) to reduce pain in patients with knee OA. The authors reported that the treatment group receiving cryoneurolysis had a statistically significant greater change in the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) pain subscale scores from baseline for up to 150 days, as compared to a sham control group. The authors reported expected adverse effects, that were transient, with mild severity, requiring no further intervention. In another study, Dasa, et al. introduced preoperative cryoneurolysis to the ISN and the anterior femoral cutaneous nerve (AFCN) prior to TKA in patients with knee OA and observed a statistically significant reduction in hospital stay, a decrease in prescribed opioids, and less knee symptoms as compared to control. These results provide clinical evidence, suggesting that cryoneurolysis treatment is a safe procedure, that may reduce both pain and symptoms in patients with knee OA. Further prospective randomized controlled studies, with adequate power are needed to confirm the efficacy and safety of cryoneurolysis treatment in patients with knee OA.

In Denmark, a neuromuscular exercise program (GLA:D) has been implemented in the national clinical guidelines by the Danish Health Authority, for the treatment of knee and hip OA in clinical practice. Recent studies show that exercise reduce pain and improve function in people with knee or hip OA. Despite of these reports the beneficial effects remains moderate with difficulties in maintaining these effects at longterm follow-up. In addition the implementation of the exercise program is not optimal and includes a significant discontinuation rate for patients reporting high pain levels. In this line, pain and muscle weakness, among others, have been reported to be major barriers for physical exercise. The application of cryoneurolysis treatment as an effective pain reducing treatment prior to a standardized exercise program could perhaps provide significant pain relief and improve patients' ability to produce force, resulting in improved adherence, exercise effectiveness and long-term benefits of both therapies. Currently, no studies have reported the effects of cryoneurolysis treatment on pain and functional performance in conjunction with a standardized exercise programme, in patients with knee OA.

Description of the cohort

The cohort consists of patients with chronic pain (>6 months) and knee OA confirmed by radiography (grade 2-4), referred to GLA:D by their general practitioner prior to assessment of surgery eligibility at the hospital. 

Data and biological material

The primary outcome is the change in knee pain intensity score (VAS), measured from baseline to post cryoneurolysis treatment. Secondary outcomes include changes in pain characteristics, functional performance, quality of life, analgesic use and adverse effectse measured from baseline, to post cryoneurolysis and to 3, 12 and 24 month after completion of an exercise program (GLA:D).

Collaborating researchers and departments

Unit of Health Sciences, Hospital of Southwest Jutland & the Department of Regional Health Research, University of Southern Denmark

• Associate professor, Bibi Gram, PhD

Pain Clinic, the Department of Neurology, Hospital of Southwest Jutland

• Carsten Kock-Jensen, MD

Department of Anesthesiology, Hospital of Southwest Denmark

• Rasmus Gymose Berthelsen, MD

Department of Orthopedics, Hospital of Southwest Denmark

• Professor Niels Wedderkopp, PhD, MD

Pain Center South, Department of Anesthesiology and Intensive Care, Odense University Hospital

• Associate Professor, Gitte Handberg, MD

• Morten Blichfeldt-Eckhardt, Post doc, MD

Department of Radiology, Odense University Hospital

• Associate professor, Ole Graumann, PhD, MD