Genicular Nerve Ablation Review Using Cooled-Radiofrequency Nerve Ablation

Abstract

Osteoarthritis (OA) is globally the most prevalent joint disease and causes patients great pain, limited joint mobility, and psychological distress. Short- and long-term therapies like steroid injections and arthroplasty exist, respectively. Joint arthroplasty can effectively treat symptomatic end-stage OA, but most patients do not go through with surgery because they are not qualified, have comorbidities, or do not wish to undergo surgery. As a result, patients can turn to opioid agonists for pain relief, which contributes to the growing opioid epidemic that mars our communities. Cooled radiofrequency ablation (C-RFA) is an effective treatment modality that can alleviate the pain associated with moderate to severe OA, especially in patients who have tried and failed conservative therapy. This review article elucidates the benefits of C-RFA, while also walking through the technical steps to performing the procedure. For patients suffering from debilitating joint OA, especially of the knee, C-RFA is a minimally invasive procedure that ensures pain relief.

Knee osteoarthritis (OA) affects 22.9% of adults aged 40 years and over in the whole world (∼654 million adults), with 15.8% of that population being from North America. ¹ The knee is a synovial joint that comprises of bone (femur, patella, and tibia), cartilage (meniscus), ligaments, and synovial fluid. Knee OA is caused by cartilaginous degeneration leading to osseous compression from weight-bearing forces. Further research has revealed that knee OA is multifactorial, showing that knee OA can be attributed to inflammation and biochemical and metabolic changes, which can lead to pain. ² The change in synovial environment (with release of inflammatory cytokines, nerve growth factors, and antibodies) can irritate the nerves surrounding the knee joint, leading to the characteristic knee pain that so many patients experience. ^{3 4} Knee OA risk factors include obesity, old age, diabetes, and muscle weakness. ⁴ Due to population aging and the rise in obesity rates, knee OA will continue to be the cause of knee pain. In one cross-sectional study, higher degrees of obesity (overweight vs. stages of obesity) led to higher degrees of pain which prevented those patients from exercising, an uncomfortable cycle of not exercising and not losing weight. ⁵ Knee OA usually presents with chronically progressive knee pain, morning stiffness, and reduced function, along with painful range of motion and crepitus. ^{4 6} Pain can be located anywhere from the distal femur to the proximal tibia. Prolonged activity or repetitive bending will cause it to progressively worsen. ⁷

Knee OA management principally aims at pain reduction with improvement in knee function and range of motion through nonoperative or operative treatment. Nonoperative pain management options that seem to have the most benefit are patient-directed exercise routines and weight loss as seen in the Look AHEAD study which reduced pain and improved physical function in diabetic overweight and obese patients 12 months after starting the study ^{2 8 9 10} ( Fig. 1 ). The exercise and weight loss routines can be painful, however, and many patients cease the exercise or require combining other conservative management options due to pain or lack of resources. These include medical treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or intra-articular injections with hyaluronic acid or corticosteroids (intra-articular corticosteroid [IAC]). For patients with an 8-year mean duration of knee OA, NSAIDs have proven to reduce knee pain by 12% on the WOMAC scale 6 months after taking NSAIDs. ¹¹ However, NSAIDs are used only when patients feel pain, rather than continuously scheduled. NSAIDs also have increased risks in patients with gastrointestinal disease, prior cardiac procedures, or patients with hypersensitivities. ¹² Patients have turned to opioid usage for knee OA pain, contributing to the opioid epidemic that has plagued the country. There was an increased odds ratio of 5.10 (95% confidence interval, 4.67–5.58) of chronic opioid usage, defined as filling 10 or more opioid prescriptions or more than 120 days' supply in the first postoperative year, in patients who received total knee arthroplasty (TKA) than nonsurgical patients. ¹³ In a recent cohort-based population study in Sweden, the prevalence of knee or hip OA patients taking opioids for at least a year was twice as much as patients without OA. ¹⁴ Opioid addiction incurs a grave national crisis that costs the economy around $78.5 billion a year. ^{15 16}

Fig. 1.

Summary of 2019 American Society of Rheumatology and Arthritis Foundation guidelines for the management of osteoarthritis. Conservative management options include a combination of weight loss, nonopioid pain medication, and physical therapy, with intra-articular steroid injections considered second line. If above options cannot adequately control OA-related symptoms, patients are considered for joint replacement surgery. Alternative pain management options are needed to bridge patients to surgery or manage OA-related symptoms in patients who cannot undergo surgery. NSAID, nonsteroidal anti-inflammatory drug.

More invasive conservative management options include intra-articular injections with corticosteroids or hyaluronic acid. IACs are theorized to reduce the inflammation of the synovial joint via reduction in interleukin-1, leukotrienes, and other proinflammatory mediators in knee OA. ² However, they can be cytotoxic to the cartilage, leading to worsened knee OA. ¹⁷ Although a common modality for alleviating knee pain, the guidelines supporting its use is conflicting between the Osteoarthritis Research Society International (OARSI), American College of Rheumatology (ACR), and American Academy of Orthopedic Surgeons (AAOS). ^{18 19 20} Hyaluronic acid has been used for “viscosupplementation” for the articular cartilage, but similar to IACs, there is disagreement on its efficacy. ^{18 19 20}

The next step in knee OA pain management is the surgical procedure TKA. There are approximately 500,000 TKA procedures done annually, making it one of the most common procedures in the United States. ²¹ In their randomized controlled trial of TKA procedures, Skou et al concluded that patients who had TKA surgery had greater pain reduction and improvement in function (greater Knee Injury and Osteoarthritis Outcome Scores [KOOS]) after 12 months than patients who were just treated conservatively (exercise, dietary changes, insoles, and nonopioid pain medication). ²² TKA procedures have shown to be cost-effective in the Medicare-aged population but is still a costly procedure with lifetime costs rising from $37,100 before TKA to $57,900 after TKA. ²³ In 20% of patients after TKA, knee pain persists beyond 3 to 5 months. ²⁴ Obese patients are less likely to improve with TKA, meaning their pain will endure. ²⁵ Obesity rates continue to climb in the United States, which will only cause more knee pain in patients and requiring them to seek alternatives to manage their pain. Genicular nerve radiofrequency ablation (GNA) has become a promising alternative conservative management option in treating arthritic patients who are contraindicated to receive surgery (obese patients) or who experience joint pain even after TKA.

GNA operates via neurolysis, disruption of neural pain signal transmissions, to alleviate the pain in OA joints or patients who experience postoperative pain. There are three main methods of GNA: thermal standard (SRFA), cooled (C-RFA), and pulsed radiofrequency ablation (P-RFA). ²⁶ The SRFA probes deliver a limited ablation zone from an insulating layer surrounding the probe tip called the “coagulum” that forms an insulating layer. Because their probes operate at a set temperature of 80 °C, tissue temperatures exceed 100 °C at the electrode–tissue interface. This leads to charring and destruction of the tissue, forms the “coagulum,” from denaturation of adjacent plasma proteins, which can form a thrombus. ²⁷ The insulating layer raises tissue electrical impedance, limiting lesion size with small ovoid or elliptical ablation zones.

C-RFA uses radiofrequency probes that are internally cooled to a set temperature of 60 °C. Therefore, tissue temperatures reach approximately 77 to 80 °C at the electrode–tissue interface. The probe tip is then free of charred tissue, obviating electrical impedance. This results in larger spherical ablation zones that are five times significantly larger than SRFA (bipolar probe), which can compensate for the complexity and variability of joints ^{28 29 30} ( Fig. 2 ).

Fig. 2.

Ablative zones of different types of radiofrequency ablation. ( a ) Standard radiofrequency ablation (SRFA) imparts temperatures greater than 100 °C at the electrode–tissue interface, forming an elliptical ablation zone (red) of limited reach secondary to tissue charring. ( b, c ) RFA imparts an average temperature of 77–80 °C at the electrode–tissue interface, allowing the formation of a larger spherical ablation zone, red), and capturing a greater number of articular sensory nerve fibers. ( c ) Ablative zones generated by c-RFA are around five times those of SRFA.

Through different mechanisms, nerve regeneration occurs after peripheral nerve injury. ³¹ With articular sensory nerve ablation, nerve regeneration could lead to recurrence of chronic pain. However, nerve regeneration and pain recurrence depend on the distance between proximal axonal stump and distal axonal fibers. ³¹ Large ablation zones created by C-RFA increases the distance and decreases the risk or length of onset of pain recurrence.

Each method works by issuing different levels of thermal energy that causes tissue destruction in a calculated ablation zone to interrupt pain signals, with C-RFA ablating a larger zone twice the size of SRFA. ^{32 33} Each method can be done with monopolar or bipolar electrode probes that deliver different ablation zones, depending on the patient anatomy and physician preference. GNA targets the superior medial and superior lateral femoral nerves, the inferior medial tibial genicular nerve, and in some cases the suprapatellar genicular nerve (SPGN) branch; in one study, this four-nerve method has effectively managed knee pain from knee OA after 6 months seen in a reduction in visual analog scores (VAS). ³⁴ Kidd et al reviewed GNA for painful knee OA, but this article will discuss recent literature and studies that have since been performed to strengthen the data behind the efficacy of GNA, especially with C-RFA as well as the radiologist's role in the procedure. ³⁵ This article will review C-RFA, highlighting the current literature of the method, as well as detail the procedure techniques and considerations.

Cooled Radiofrequency Ablation

Patient Selection

Patients who are candidates for genicular nerve C-RFA therapy are those with moderate-to-severe knee OA and have failed conservative therapies like IACS, exercise, and weight loss. Other patients include those with severe comorbidities like morbid obesity (BMI ≥ 35 kg/m ² ), heart disease, and mental health issues and cannot undergo TKA surgery. Some patients also do not wish to have surgery and wish to explore other conservative options. All patients who wish to undergo the C-RFA procedure must first pass a diagnostic screening injection to confirm their candidacy for it.

Preprocedure

Patients' histories are taken and evaluated, specifically about anticoagulation status, allergies, and any other current medication usage.

Procedure

GNA creates ablation zones specifically at the superolateral (SLGN), superomedial (SMGN), and inferomedial (IMGN). A fourth nerve, the SPGN, is a potential nerve target. The SMGN and IMGN branch off of the tibial nerve, the SLGN branches off of the common peroneal nerve, and the SPGN branches off of the saphenous nerve ( Fig. 3 ). The diagnostic screening injection consists of injecting these three to four nerve sites with anesthetic. Patients who have more than 50% of pain relief (per the Likert scale) are candidates for C-RFA a few weeks later. ³⁶

Fig. 3.

Schematic showing the sensory innervation around the anterior knee joint specifically the superolateral (SLGN), superomedial (SMGN), inferomedial (IMGN), and suprapatellar genicular nerve (SPGN).

Diagnostic Genicular Nerve Block

The patient lies supine on the fluoroscopy table. The symptomatic knee(s) is flexed to 30 degrees. Using 1 to 2 mL of 2% lidocaine, a skin wheal is made, achieving superficial local anesthesia. A 22-gauge 3.5-inch spinal needle is used for the diagnostic injection at each site to block the respective nerves. For each genicular nerve block, 1.0 mL of 2% lidocaine (or 0.5% bupivacaine) is injected. To target the SLGN and SMGN sites, the concave transitions of the femoral metadiaphysis and condyles are used. ³⁷ The IMGN site is located at the concave transition in between the tibial plateau and metadiaphyseal shaft. ³⁷ The SPGN site was targeted at the anterior distal femoral diaphysis, 3 cm superior to the superior patella. ³⁴ After 15 minutes of the nerve block, patients are assessed via physical exam and range of motion to incite preprocedural pain. If at least 50% of pain is reduced, the diagnostic test is considered positive, and the patient is scheduled for C-RFA.

Procedure of GNA with C-RFA

Two to 3 weeks later, patients arrive for the C-RFA procedure, with informed consent. Similar to the diagnostic injections, patients are placed supine on the fluoroscopy table with their symptomatic knee(s) flexed to 30 degrees. They are given conscious sedation with 1 to 2 mg IV, midazolam, or 25 to 100 μg IV of fentanyl, as needed, and supplemental oxygen. One to 2 mL of 2% lidocaine is used for superficial anesthesia at each nerve site. A grounding pad is placed on the ipsilateral side of the symptomatic knee to ensure adequate C-RFA conduction, making sure to avoid areas of scar tissue, bony prominences, metal (prosthesis or electrodes), and areas of edema. The four nerves (SMGN, IMGN, SLGN, and SPGN) are ablated by first placing 50- to 150-mm 17-gauge introducer needles at each site. Then, the RFA electrode probe (18-gauge, internally cooled 4- or 5.5-mm active tip; Coolief, Halyard Health, Alpharetta, GA) inserted into the introducer needle. To ensure correct positioning with the needle maneuvers, anteroposterior and lateral fluoroscopic views are taken (making sure that 60% of the bone shaft width is covered). To reduce motor nerve ablation, motor nerve activity is stimulated at 2 Hz to 1 mA. If motor stimulation is observed (muscle twitching), the electrode probe was adjusted, and motor stimulation tested again. For deeper anesthesia before ablation, 1 mL of 2% lidocaine is injected through the introducer needles. The site is then ablated for 180 s at a temperature of 60 °C ( Fig. 4 ). ³⁴

Fig. 4.

Introducer needles are placed at the superomedial (SMGN), superolateral (SLGN), and inferomedial genicular nerve (IMGN) sites on anteroposterior ( a ) and lateral ( b ) views (red circles—target zones). The guide needle must cover at least 50% of the bone shaft width on lateral view. With the four-needle technique, the SPGN is targeted by placing one additional needle ∼3 cm proximal to the patella seen on anteroposterior ( c ) and lateral ( d ) views (arrowhead).

Postprocedure

When all appropriate sites are ablated, the patients are kept up to 2 hours to ensure no complications arise and they remain hemodynamically stable. Patients are instructed to not engage in heavy lifting of objects 5 lb or heavier for the first week, no underwater submersion at least for 5 days, and to gradually return to normal physical activity up to 2 weeks. For the first month, patients are also advised against running and stair exercises.

Complications and Limitations

With any invasive procedure (minimal or not), there is a risk for local skin infection and cellulitis. This is addressed with sterile technique during the procedure. Patients have experienced contact dermatitis to the antiseptic cleaning solution, chlorhexidine gluconate. Motor neuron injury and skin burns are potential complications. A theoretical complication from RFA that comes long term is Charcot neuropathy, but this is less of a concern in patients who are expected to have TKA shortly after the C-RFA procedure or have a short life expectancy. ³⁸ Charcot neuropathy from nerve ablation does not exist in the literature; however, RFA is a novel procedure, and long-term safety data are being studied. C-RFA forms an ablation zone that accounts for various patient anatomy, but needle placement is not always exactly precise. The main limitation in the procedure is the variable operator experience.

Efficacy of C-RFA

Numerous studies have investigated the efficacy of C-RFA in managing knee pain from OA. C-RFA has shown significant improvement in pain 12 months after treatment in a case report by Bellini and Barbieri where VAS scores decreased from 8.0 ± 1.5 to 2.2 ± 0.2. ³⁹ In the same study, Western Ontario McMaster Universities OA index (WOMAC) scores decreased from a baseline of 88 ± 1.9 to 20 ± 1.0 at 12 months. ³⁹ In a recent retrospective study, 275 patients who received geniculate nerve blocks had VAS scores significantly decrease from 8.5 to 4.2, with 65% claiming over 50% decrease in pain up to 12.5 months, after receiving C-RFA for their knee pain. ⁴⁰ These case reports and retrospective studies are at risk of selection bias and placebo effects, however. The most recent prospective randomized controlled study by Hunter et al found that 12 of 25 subjects and 11 of 18 subjects had ≥50% pain relief at 18 and 24 months, respectively, without reported adverse events. ⁴¹ This supports C-RFA's efficacy to an extended time of 24 months.

C-RFA has also been compared with other conservative pain management modalities, like IACS. In a randomized crossover clinical trial by Davis et al, 151 patients who had knee pain for at least 6 months and did not respond to conservative treatments were enrolled to receive C-RFA or IACS. ⁴² Numeric rating scale (NRS) scores for C-RFA (2.5 ± 2.3) were significantly less than IACS (5.9 ± 2.2). C-RFA's reduction in pain of 50% or greater from NRS scores was statistically greater than IACS, with 74.1 versus 16.2% of patients, respectively ( p  < 0.0001). Even at 12 months, the majority of patients treated with C-RFA originally still reported more than 50% pain reduction and significant 4.2-point decline in NRS (baseline NRS: 7.3 ± 1.2; and 12-month NRS: 3.1 ± 2.7). ⁴² From this study, C-RFA achieves pain relief sooner and longer than IACS.

C-RFA has shown greater benefit in managing knee pain than hyaluronic acid injections (HAIs). In a randomized control trial from Chen et al, 177 patients who had knee pain from OA and had positive genicular nerve block responses were enrolled to receive C-RFA or HAI and followed up for up to 12 months. ⁴³ Compared with HAI, C-RFA had significantly greater pain relief at 6 months with C-RFA and HAI NRS scores of 2.7 and 5.0, respectively ( p  < 0.0001). At 12 months, HAI and C-RFA had comparable significant decrease in pain relief (from baseline NRS scores: C-RFA NRS 2.8 and HAI NRS 3.0, p  < 0.0001). Although there was not a significant difference between the two treatments at 12 months, C-RFA had quicker knee pain relief at 6 months.

When evaluating these randomized trials, C-RFA has a higher efficacy in managing knee pain symptoms from OA, but heterogeneity in response to the treatments must be considered. Patients are qualified for C-RFA if they have a more than 50% pain reduction after receiving a diagnostic nerve block, but even after C-RFA procedures, some patients do not respond and will not have knee pain relief. ³⁴ Better understanding of predicting C-RFA response with nerve blocks and patient phenotyping would benefit patient selection for C-RFA procedures. This would minimize clinical trial and error and improved conservative outcomes. ⁴⁴

Conclusion

Knee OA is a debilitating disease that continues to affect millions of lives throughout the world. Pain management requires a combination of treatments that escalate progressively to surgery, which many patients cannot, or choose not to, pursue. Patients need to have an additional conservative management that is effective, and does not have long-term complications with continued use, which C-RFA can provide. With IACS, the decreased knee pain allowed patients to gain more knee function and mobility, which has hopeful implications in C-RFA's pain management abilities. ⁴⁵ However, the pathophysiology of knee OA is complex and is progressively elucidated with ongoing research. With its complexity, multiple treatment strategies will be explored that involve physical, pharmacological, and interventional treatments that address different aspects of the pathophysiology. ⁴⁶ For C-RFA, the next step in research should investigate identifying ideal patients who will respond to the treatment and have full confidence that their knee pain will be managed with the procedure.