Narrative review of radiofrequency ablation applications in peripheral nerves

Introduction

Background

Chronic pain is an often-complex affliction that poses a persistent challenge at both the individual and societal levels. It is one of the most common reasons adults seek medical care, affecting an estimated 11–40% of all Americans over 18 and costing the United States health care system nearly half a trillion dollars a year in both medical expenses and lost wages (1). In addition to diminishing the perceived quality of life for those experiencing chronic pain, it further leads to an increased dependence on opioids, higher rates of anxiety and depression, and decreased mobility (1).

Chronic pain can be further classified into the subcategories of nociceptive and neuropathic pain depending on its mechanism. Nociceptive pain is characterized by damage to non-neural tissue that results in nociceptor stimulation while neuropathic pain arises from a lesion or damage to the somatosensory nervous system (2). In the context of peripheral nerves, there are a multitude of serious conditions that may give rise to both pain types. Neuropathic pain can be derived from autoimmune diseases such as multiple sclerosis and Guillain-Barre syndrome as well as metabolic diseases such as diabetes and the associated peripheral diabetic neuropathy (3,4). Additionally, a variety of infections [e.g., shingles and human immunodeficiency virus (HIV)], traumas, cancers, and cancer treatments (e.g., chemotherapy-induced peripheral neuropathy) can further lead to neuropathic pain (3,4). Nociceptive pain, in contrast, is more associated with conditions such as arthritis and pain from inflammation (3). This variability in chronic pain causes, particularly for neuropathic conditions, represents one of the central challenges to achieving satisfactory treatment (5).

Rationale and knowledge gap

When conservative management of chronic pain fails or when patients are not suitable candidates for surgical treatments, an alternative approach has emerged using radiofrequency ablation (RFA). RFA functions by generating thermal lesions at specific nerve targets thereby disrupting the transmission of pain signaling and providing relief to the patient (6). Prior to the RFA, a temporary diagnostic nerve block should be conducted to ensure that the RFA is targeting the appropriate pain source. Typically, between one to two diagnostic nerve blocks are performed, with recent literature suggesting one block is sufficient for determining if a patient will experience relief from nerve ablation (7). RFA itself is an umbrella term under which several varieties of the technology exist, including conventional, pulsed, and cooled RFA (CRFA). Previous literature has demonstrated the efficacy of RFA as an effective minimally invasive modality for the management of numerous chronic pain conditions via the ablation of pertinent sensory nerve pathways (8).

Objective

The purpose of this review is to outline recent advancements and trends in the use of RFA in peripheral nerves for the treatment of chronic pain conditions. We present this article in accordance with the Narrative Review reporting checklist (available at https://apm.amegroups.com/article/view/10.21037/apm-24-8/rc).

Methods

A literature search was done using the PubMed database using various combinations of the words “Radiofrequency”, “Ablation”, “Pain”, “Chronic”, “Peripheral”, and “Nerve”. Articles written in English dated from 2018 to 2023 discussing the application of RFA on peripheral nerves focusing on alleviating chronic pain were included. Literature reviews, systematic reviews, meta-analyses, and non-English articles were excluded. Articles dated from 2017 and older were excluded in order to maintain a focus on recent advancements. Results were further screened by relevance and full article availability. The included articles were then sorted and reviewed based on anatomical region and associated conditions. The summarized approach can be seen in Table 1.

RFA interventions by anatomical location and condition

Facial pain and trigeminal neuralgia (TN)

TN, also known as tic douloureux, is a neuropathic condition characterized by paroxysmal pain in the face that has been likened to that of electric shocks and cuts from a knife (9). While the cause of the condition is thought to arise from compression of the trigeminal nerve, most cases are deemed idiopathic, with the exact cause remaining unclear (10). The condition is typically managed through a pharmacological approach using medications such as carbamazepine and oxcarbazepine; however, in individuals experiencing intractable pain that does not respond to medication, alternative approaches must be taken (11). In an article by Mansano et al., the efficacy of RFA as a treatment for TN was investigated via a prospective, randomized, double-blind, sham-controlled clinical trial. Thirty patients were randomly assigned to receive either percutaneous trigeminal RFA via the foramen ovale (FO) or a sham treatment in which all the steps were the same as the RFA group without the creation of a lesion. After 1 month, the mean numerical rating score (NRS) decreased from 9.2 to 0.7 in the RFA group and 8.9 to 5.8 in the sham group. Results of the study revealed a statistically and clinically significant reduction in pain in the RFA treatment group over the sham group (12). For the treatment of V2 TN, researchers Xue et al. conducted a non-randomized controlled clinical trial comparing radiofrequency thermocoagulation (RFT) of the maxillary nerve through the foramen rotundum (FR) with RFT of the Gasserian ganglion through the FO. In total, 80 patients participated in the study, with 40 assigned to each group. All 40 patients in the FR group had no facial pain at 1 week, 6 months, and 1 year post-surgery. In the FO group, four patients did not experience pain relief, and another three patients relapsed after 1 year. The outcomes of this study indicate that ablation of the maxillary nerve through the FR was more efficacious than ablation of the Gasserian ganglion in treating V2 TN (13).

Two studies were reviewed that investigated methods for improving puncture guidance. Researchers Wang et al. created a computer-assisted design (CAD) template to assist in the performance of RFT for V2 TN. The template was used to guide the RFT lead through the FR for RFT of the maxillary nerve. The study was retrospective case-controlled and consisted of 38 TN patients assigned to either a treatment group with treatment guided by the template or a free-hand-guided control group. Between groups, there was no difference in pain outcomes despite the treatment group having a shorter average puncture and operation time. Results of the study demonstrated potential in the use of CAD to create templates that can assist with accurate punctures for RFA treatment (14). Similarly, a study by Liang et al. sought to investigate the use of ultrasound as a supplementary tool to C-arm fluoroscopy in the guidance of RFT through the FO for selective targeting of the semilunar ganglion. The randomized control trial showed that ultrasound combined with C-arm imaging had fewer punctures, less time to reach the semilunar ganglion, and less radiation exposure compared to C-arm alone. Despite the improvements in these outcomes, there was no significant difference in NRS scores between ultrasound combined with C-arm and C-arm alone (15).

Headaches and occipital neuralgia

Several studies investigated the use of RFA for the treatment of occipital neuralgia and headache pain. In one retrospective analysis by Abd-Elsayed et al., researchers analyzed the efficacy of occipital nerve RFA in 277 patients for reducing pain and associated headaches that were diagnosed as stemming from occipital nerve neuralgia. From pretreatment to a post-operative 6-month follow-up, the mean reduction in patient-reported pain was 63.53% [standard deviation (SD) =36.37%] and was found to be statistically significant (16). Similar success in treating neuralgia-related headache pain has been seen in the RFA of several other pericranial nerves, including the supraorbital, supratrochlear, infratrochlear, and infraorbital (17,18). In another retrospective analysis, Guo et al. found that low-temperature plasma RFA (LTPRFA) at the sphenopalatine ganglion was an effective intervention for chronic and episodic cluster headaches (19). Of the 26 patients with chronic cluster headache, at 1 day, 12 months, and 24 months post-operative, the percentage of patients experiencing partial or complete pain relief was 92.3%, 92.3%, and 73.1%, respectively. Of the 50 patients included with episodic cluster headache, the percentage of individuals experiencing partial or complete relief at the 1-day, 12-month, and 24-month follow-up was 73.1%, 84%, and 68%, respectively (19).

Hip and pelvis

Literature related to the treatment of hip and pelvic pain primarily consisted of case reports. In one case series by Abd-Elsayed et al., researchers investigated the use of CRFA for intraarticular hip pain related to greater trochanteric pain syndrome (GTPS). GTPS itself is a common diagnosis in patients with chronic hip pain and encompasses several different conditions (20). In the series, eight patients with GTPS received CRFA of the nervus femoralis trochanteric branch. Results from the series were promising, with all patients experiencing pain relief up through 2 months post-operative and with no noted negative outcomes (20). In another case report by the same primary author, researchers documented two patients with intractable hip pain related to GTPS. Both patients received CRFA of the trochanteric branch of the femoral nerve. The first patient had a baseline NRS of 8 with a 1-month follow-up score of 2 and a 3-month follow-up score of 3. Patient two had a baseline NRS of 9 and subsequently experienced complete pain relief at 1 and 3 months post-procedure (21). Lastly, Neubauer et al. documented a complication in the use of RFA for the treatment of post-operative inguinal neuralgia. The report outlines a case in which a patient underwent bilateral ilioinguinal and iliohypogastric nerve ablation, which led to inadvertent thermal damage with delayed small bowel perforation. The primary conclusion of the report was the suggestion of alternative mechanisms by which to increase the distance between the ablation site and nearby organs (22).

Knee

The most cited peripheral nerve application of RFA was for the treatment of chronic knee pain. One of the largest causes of chronic knee pain is knee osteoarthritis (OA), which is a degenerative condition that affects the joint’s cartilage and subchondral bone. OA progression leads to stiffness, pain, loss of function, and ultimately a worse quality of life (23). For end-stage knee OA, the preferred treatment is often total knee arthroplasty, however, novel and less invasive approaches are needed in cases where patients are not suitable candidates for the procedure (24). RFA of the genicular nerves (superomedial, superolateral, and inferomedial genicular nerve) has emerged as an effective alternative for patients with chronic knee pain from OA (23).

Of the reviewed studies, several investigated the efficacy of RFA in comparison to other treatments for palliation of OA knee pain. One study by Chen et al. compared the use of CFRA with a single injection of hyaluronic acid in a multicenter randomized clinical trial. One hundred and seventy-seven patients identified as positive responders to a diagnostic nerve block (>50% reduction in pain) were randomly assigned to receive either a single injection of hyaluronic acid or CRFA on four genicular nerves. Results of the study show that 71% of patients treated with CRFA experienced a >50% reduction in their NRS pain rating compared to 38% in the hyaluronic acid group (P<0.0001) (25). In a prospective observational extension of the study by Chen et al., researchers Lyman et al. sought to investigate the long-term durability of the pain relief associated with CFRA. In the study, 32 patients completed an 18-month follow-up visit, with 69% reporting a ≥50% reduction in their NRS score. Twenty-seven patients completed a 24-month follow-up visit, with 63% reporting a ≥50% reduction in their NRS score. The results of this prospective extension study demonstrate sustained pain relief in patients treated with CRFA up to 24 months post-procedure (26). Along with hyaluronic acid, Elawamy et al. concluded RFA to be superior to intra-articular platelet-rich plasma injection, and Davis et al. found CRFA had more favorable outcomes in NRS score reduction at 6 months than intra-articular corticosteroid injections (27,28).

Several studies further investigated differential outcomes among variations of RFA. A study by Kim et al. sought to compare ultrasound vs. fluoroscopy-guided RFA when performing genicular nerve blocks. Researchers utilized a prospective randomized comparison design in which they randomly assigned 80 patients to either ultrasound or fluoroscopy-guided RFA. Results of the study showed no significant difference in NRS-11 or Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores between the groups. The primary conclusion of the study is that either imaging device may be used while performing a genicular nerve block for chronic knee pain. However, radiation exposure associated with fluoroscopy may make ultrasound a more favorable approach (29). Another study by Vanneste et al. sought to compare the outcomes of conventional RFA with CRFA. The double-blind, non-inferiority, pilot, randomized control trial is the first to directly compare the two modalities in the treatment of chronic knee pain from OA. The study involved randomly assigning 49 patients to an RFA treatment, with the primary outcome being the proportion of patients experiencing ≥50% pain reduction at 3 months post-procedure. Results from the study did not show a statistically significant difference in the primary outcome between the two approaches (23). Lastly, researchers Mohamed et al. compared a novel three-needle technique with the conventional single-needle approach to RFA for knee OA. As mentioned previously, treatment of knee pain from OA commonly involves ablation of the superior medial, superior lateral, and inferior medial genicular nerves (23). The conventional approach involves the use of a single needle for ablation of each nerve (30). Researchers investigated outcomes if three needles were used in conjunction on each nerve, as opposed to the typical single needle. A prospective parallel single-blind randomized design was used in which 50 patients with OA were randomly assigned to the conventional or novel technique. Results of the study showed the three-needle technique had significant improvements in visual analogue scale (VAS) and WOMAC scores over the conventional single-need method through 6 months post-procedure (30).

While most of the literature investigated the treatment of chronic knee pain from OA, particularly for patients that were not suitable candidates for surgical interventions, one study by Mishra et al. investigated whether RFA of genicular nerves pre-operatively could have analgesic effects postoperatively in total knee arthroplasty. In this single-center, prospective, randomized, sham-controlled, double-blind pilot trial, 60 patients were randomly assigned to receive conventional RFA or a sham in the weeks prior to their total knee arthroplasty. The outcomes of the trial showed that there was no significant difference between the RFA or sham groups in their pain intensity at 6 weeks post-surgery. Researchers concluded that preoperative ablation of the superior medial, superior lateral, and inferior medial genicular nerves did not lead to clinically significant pain improvement 2–6 weeks post-total knee arthroplasty (31).

Abdomen

The primary area of research relating to applications of RFA in the abdomen dealt with chronic pain derived from pancreatic cancer and malignant carcinoid tumors (32). Initial case reports show promising treatments for severe abdominal pain that can arise from these gastrointestinal cancers. In a report by Al-Jumah et al., a 50-year-old male patient with severe abdominal pain from pancreatic cancer underwent RFA of the bilateral splanchnic nerves. The patient experienced an 80% reduction in his pain and had sustained relief up through 3 weeks (33). In a similar case, researchers Noor et al. documented a 61-year-old female with severe abdominal pain from a malignant carcinoid tumor. Following successful blocks of the superior hypogastric plexus and splanchnic nerve, the female underwent RFA of these same nerves. Following ablation, at the 1-month follow-up, the patient reported an 80% improvement in pain and had completely stopped all opioids (32). Two randomized trials were reviewed pertaining to RFA for pancreatic cancer-derived abdominal pain. In a study by Amr et al., researchers compared RFA to alcohol-based chemical neurolysis of the bilateral splanchnic nerves. The team randomly assigned 60 patients to receive either treatment. Results of the study showed significant reductions in upper abdominal pain for both groups. However, RFA led to longer-lasting relief and worked in a greater percentage of patients compared to chemical neurolysis (34). Similarly, a randomized single-blind control trial by Bang et al. found RFA at the celiac ganglion to be a more effective analgesic treatment for pancreatic cancer pain than celiac plexus neurolysis (35).

Miscellaneous

Other applications of peripheral RFA include the treatment of neuroma-related pain. In a clinical trial by Pu et al., researchers conducted ultrasonography-guided RFA on patients who had undergone amputations and were subsequently afflicted with painful stump neuromas. Eighteen patients were included, with results of the study showing RFA was an effective treatment in relieving post-amputation pain, including residual and phantom limb pain (36). Several case reports documented the treatment of other peripheral neuralgias. In one, Abd-Elsayed et al. reported the successful treatment of intercostal neuralgia pain in two different patients through RFA of intercostal nerves (37). In a similar case series, Fiala et al. treated intercostal neuralgia using CRFA rather than conventional RFA. Of the six total patients that received CRFA of the intercostal nerves, the average reduction in pain was 81.3% (38). Along with intercostal neuralgia, patients with sural neuralgia resistant to conservative treatment have also been effectively treated with pulsed RFA (39).

In a case report by Toropchyn et al., a patient with Ewing sarcoma affecting his jaw bones received RFA of the Gasserian ganglion for the treatment of associated jaw pain. Postoperatively, the patient experienced 80% relief in pain symptoms, which persisted for 4 months. As mentioned previously, the Gasserian ganglion is a common ablation target for the treatment of TN; however, it has not been previously documented in the treatment of pain associated with Ewing sarcoma afflicting the jaw (40). Lastly, a retrospective analysis by Abd-Elsayed investigated the use of RFA for the treatment of meralgia paresthetica. Six patients underwent a diagnostic block, followed by RFA of the lateral femoral cutaneous nerve. Results of the study showed statistically significant reductions in pain immediately following the procedure and at 1-month post-operative. The 2-, 3-, and 6-month follow-ups, however, did not show a statistically significant reduction in pain compared to pretreatment levels (41).

Conclusions

There is a large gap in the number of studies for RFA and the generalizability of its use depending on anatomical location and condition. Further research, particularly double-blind randomized controlled trials, should be conducted to investigate the treatments proposed by the case reports included in this review. This includes anecdotal reports of success in treating conditions such as occipital, inguinal, and sural neuralgia. Additionally, the lack of large sample sizes is a significant limitation of the existing research. It is also important to note that this review solely focuses on primary research within the last 5 years, and as such does not represent the full range of documented peripheral nerve applications for RFA. Other literature reviews showcase applications for peripheral nerve RFA in the treatment of joint pain arising in regions such as the ankle (42) and shoulder (43), as well as additional neuralgias (44). That said, the studies included in this report indicate that RFA continues to be an effective treatment for a variety of chronic pain conditions related to peripheral nerves.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Annals of Palliative Medicine, for the series “Advances in Radiofrequency Ablation”. The article has undergone external peer review.

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://apm.amegroups.com/article/view/10.21037/apm-24-8/rc

Peer Review File: Available at https://apm.amegroups.com/article/view/10.21037/apm-24-8/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://apm.amegroups.com/article/view/10.21037/apm-24-8/coif). The series “Advances in Radiofrequency Ablation” was commissioned by the editorial office without any funding or sponsorship. A.A.E. served as the unpaid Guest Editor of the series and serves as an unpaid editorial board member of Annals of Palliative Medicine from June 2022 to May 2024. He also serves as a consultant for Avanos and receives consulting fees. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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