Dual-Modality Nerve Ablation: Preoperative Radiofrequency and Cryoneurolysis for Enhanced Pain Relief in Total Knee Arthroplasty

Dual-Modality Nerve Ablation: Preoperative Radiofrequency and Cryoneurolysis for Enhanced Pain Relief in Total Knee Arthroplasty | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Dual-Modality Nerve Ablation: Preoperative Radiofrequency and Cryoneurolysis for Enhanced Pain Relief in Total Knee Arthroplasty Paul Bonilla, Juan Pablo Flanagan, Anesu Murambadoro, Victoria Elizondo, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8888424/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background Post-operative pain management following total knee arthroplasty often fall short in addressing deep and superficial pain sources effectively. Cryoneurolysis and radiofrequency ablation (RFA) are established techniques that induce Wallerian degeneration to disrupt pain pathways but are rarely used in tandem. This study aims to investigate a novel dual-modality preoperative pain management technique combining RFA and cryoneurolysis to improve patient outcomes and reduce opioid dependence postoperatively. Methods A prospective observational study was performed on patients undergoing cryoneurolysis and radiofrequency ablation before primary TKA from March 2025 – December 2025. Primary outcome measures were obtained through surveys investigating pain through numerical rating scores (0–10) and functionality through Knee Injury and Osteoarthritis Outcome Score Joint Replacement (KOOS JR) scores. All information was collected from patients undergoing standard of care TKA. Pre-operative data was obtained during the first cryoneurolysis and radiofrequency ablation visit while post-operative data was electronically through Qualtrics 12 weeks post cryoneurolysis and radiofrequency ablation. Results 25 patients completed baseline surveys and 16 provided 120-day post-procedure data. Mean numeric pain scores decreased from 4.6 ± 2.4 to 1.9 ± 1.6 (p = 0.0001); in the 16 patients with paired data, pain decreased by 2.5 ± 3.2 points (paired t = − 3.14, p = 0.007). KOOS JR scores improved from 49.3 ± 17.8 to 72.3 ± 16.7 (p = 0.0002); among paired patients, KOOS JR increased by 26.1 ± 20.6 points (paired t = 5.08, p = 0.0001). These findings demonstrate large, statistically and clinically significant improvements in knee pain and function 120 days after preoperative cryoneurolysis and radiofrequency ablation. Conclusion The integration of these two individually successful techniques capitalizes on their respective strengths and facilitates an effective postoperative pain management strategy: reduced pain, decreased opioid consumption, and increased range of motion. The implementation of this dual approach offers significant progress in orthopedics and pain management while addressing the opioid epidemic and rising healthcare costs that come with longer hospital stays and complications. Further research is warranted to investigate long-term efficacy. Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction 1.1 Overview of TKA Over 600,000 total knee arthroplasty (TKA) surgeries are performed annually in the United States [1]. This procedure provides significant pain relief for patients suffering from debilitating osteoarthritis or joint degeneration. Surgeons replace damaged articular cartilage with prosthetic components. Although this surgery provides pain relief and increased mobility, challenges persist. Postoperative pain, stiffness, and inflammation can last for weeks, which can negatively impact rehabilitation and recovery. Although there are numerous pain management strategies, reaching a balance between effective analgesia and minimizing adverse effects remains a critical issue. The pain experienced after TKA is multifaceted, arising from both deep articular structures and superficial tissues. Deep genicular nerves, including branches of the femoral, sciatic, and common peroneal nerves, contribute significantly to articular knee pain. Superficial nerves branching from primary contributors to incisional and neuropathic pain. These varied pain sources highlight the need for a comprehensive approach to address multiple nerve targets effectively. 1.2 Anatomy Innervation of the knee includes nerves collectively referred to as the superficial and deep genicular nerves. The superficial genicular nerves are responsible for innervation of the anterior knee. Treatments involving these nerves can improve superficial incisional pain. They include the infrapatellar branch of the saphenous nerve (ISN), the anterior femoral cutaneous nerve (AFCN), and the lateral femoral cutaneous nerve (LFCN) (Fig. 1). Figure 1. Targeted superficial nerves. Reprinted with permission from NYSORA. The deeper genicular nerves include the superior medial genicular nerve (SMGN), terminal branch of the nerve to the vastus medialis which branches off the femoral nerve, superior lateral genicular nerve (SLGN), a direct branch off the sciatic nerve proximal to its bifurcation into the tibial and peroneal nerves, and inferomedial genicular nerve (IGN), a branches off the sciatic nerve [2] (Fig. 2). Figure 2. Targeted deep genicular nerves. Reprinted with permission from NYSORA. These peripheral nerves are surrounded by Schwann cells that aid in sensory signal transduction and promote axonal regeneration. The inevitable pain that comes from surgical incisions and removal of tissue is a result of the activation of pain signals through the transmission of action potentials to the spinal cord and brain [3]. Interventions such as cryoneurolysis and radiofrequency ablation target these peripheral nerves to induce physiological changes such as Wallerian degeneration. In this process, the myelin sheath surrounding an axon breaks down leading to clearance of debris by macrophages [4]. In the weeks to months following injury, Schwann cells are realigned and allow for a growth environment in which axons are regenerated[4]. 1.3 Overview of Cryoneurolysis Cryoneurolysis involves the induction of Wallerian degeneration through a minimally invasive technique that freezes the peripheral nerves. The Iovera is a handheld device which includes hollow, closed-tip needles used to directly target designated nerves. The handpiece contains a cartridge of liquid nitrous oxide which, when converted into a gas by the device, creates a temperature approaching − 87°C at the needles to produce a 5 mm ice ball under the skin. When this ice ball comes in contact with the target nerves, Wallerian degeneration is induced [5]. The cold therapy affects the axon and the myelin sheath but not the endoneurium, allowing for the predictable regrowth of the axon and myelin sheath along the endoneurium [5]. Figure 3. Myelin Sheath and Wallerian Degeneration. Reprinted with permission from Pacira Pharmaceuticals. Because Wallerian degeneration leads to axonal loss by about 36 hours, the procedure is typically done a minimum of 3–5 days preoperatively. Because repair can take 90 days or more, the procedure is sometimes done several weeks preoperatively [6]. Perioperative cryoneurolysis in combination with standard multimodal pain management has significantly improved outcomes for patients undergoing TKA. With targeting the ISN and AFCN, patients have exhibited markedly reduced PROMIS pain intensity scores at two-week post-surgery, shorter hospital stays and significantly less knee symptoms [5]. These specific nerves have been chosen because they lie in predictable locations allowing for effective targeting with the cryoneurolysis procedure. Because this procedure is primarily done on sensory-only superficial genicular nerves, motor function is preserved [5]. Figure 4. Insertion of Iovera probe under ultrasound guidance. Reprinted with permission from Pacira Pharmaceuticals. This detail is crucially important as patients require motor preservation for their rehabilitation. On average, cryoneurolysis results in an average pain relief duration of 3 months [7]. Clinical studies have demonstrated its effectiveness in reducing opioid consumption and pain scores postoperatively [5,8,9]. A retrospective review of patients who underwent preoperative cryoneurolysis revealed a 35% reduction in opioid use at two weeks and a 36% reduction at six weeks, alongside notable improvements in reported pain scores [10]. However, in this study, patients treated perioperatively with cryoneurolysis required opioid refills at two-week postoperative marks, likely due to receiving lower total morphine milligram equivalents. Despite this, a pronounced tapering of opioid use was observed at the six-week mark, demonstrating a reduced risk of long-term opioid dependence. This finding highlights the need for strategies that can enhance early pain-relief effects of cryoneurolysis while maintaining benefits in minimizing opioid consumption over time such as improved targeting of all nerves that contribute to postoperative knee pain. 1.4 Overview of Radiofrequency Ablation Radiofrequency ablation (RFA) has been used to treat chronic pain, including back pain, for decades and is a well-established pain management technique. This ablation method utilizes a specialized probe to deliver heat through electrical currents to ablate sensory nerves [11]. The goal temperature of this method ranges from 60°C − 90°C [12]. The technique begins with placement of a thin, insulated needle (cannula) equipped with an electrode at its tip which is guided to the target nerve utilizing imaging guidance. The heat generated creates a lesion in nerve tissue, effectively disrupting the ability to transmit pain signals. At typical temperatures and durations, such as 80° C for 90 seconds, connective-tissue layers such as the endoneurium, perineurium and epineurium are left largely intact. This allows for the repair of neural tissue along a predictable pathway and reduces the risk of neuroma formation. Radiofrequency ablation is primarily used to target deeper genicular nerves instead of superficial genicular nerves due to the risk of a burn injury to the skin. Targeting deep nerves is important because superficial nerves may not be the primary source of pain, while targeting deeper nerves more involved in pain pathways can provide more effective and lasting relief [13]. Studies have highlighted the efficacy of RFA in treating knee osteoarthritis pain, which is usually done under fluoroscopy or ultrasound guide [13]. Patients treated with RFA have reported significant reduction in pain, as measured by Visual Analog Scale (VAS) scores, and improvements in functional outcomes [13–15]. 1.5 Combination Technique A dual-modality approach of cryoneurolysis and radiofrequency ablation offers an innovative approach to managing preoperative pain in patients undergoing total knee arthroplasty. Through this method, superficial genicular nerves can be targeted through cryoneurolysis and deeper genicular nerves can be targeted using radiofrequency ablation. Cryoneurolysis offers rapid pain relief lasting 3 months whereas radiofrequency ablation has been shown to offer significant pain relief for 6 months or longer in patients with chronic knee pain [7,16]. The integration of these two techniques capitalizes on their respective strengths and facilitates an effective postoperative pain management strategy: reduced pain, decreased opioid consumption, improved range of motion for better rehabilitation. These techniques have been traditionally employed for relief of knee pain in patients that are refractory to conservative care such as nonsteroidal anti-inflammatory use or steroid injections and who are not candidates for joint replacement or wish to defer such surgery. More recently, these techniques have been used for adjunctive relief of post-operative pain following total knee replacement [9]. This combination can reduce the need for post-operative opioids, which may be a primary goal for some patients who do not tolerate such medications. While some orthopedic surgeons may express hesitancy towards a percutaneous technique within days or weeks of surgery, key aspects of the procedure can allay any infection-control or other concerns. In particular, it is important to note that these nerves are targeted entirely in extra-articular locations, and that no steroid is required. Methods 2.1 Study Design A prospective observational cohort study of patients undergoing cryoneurolysis and radiofrequency ablation as part of preoperative management before TKA between March 2025 and December 2025 was performed at a single outpatient practice. All information was collected from patients undergoing standard of care TKA by a fellowship trained orthopedic surgeon in Austin, Texas. The study was approved by The University of Texas Rio Grande Valley School of Medicine Institutional Review Board (IRB-24-0506). Inclusion criteria included patients over 18 years old who were able to read and understand English. Prior to their cryoneurolysis procedure, eligible patients were invited to participate by scanning a QR code displayed at check-in. Participation was entirely voluntary and had no impact on access to care, the decision to perform cryoneurolysis/RFA or TKA, or any aspect of perioperative management. Patients who completed the baseline survey on the day of the procedure, prior to cryoneurolysis, were enrolled in the study cohort. 2.2 Outcomes The QR code directed patients to a Qualtrics survey where patients rated their current knee pain on an 11-point numeric rating scale (NRS) from 0 to 10, where 0 = “No pain” and 10 = “Worst pain possible.” Responses such as “0 – No Pain” and “10 – Worst Pain Possible” were coded to numeric values 0 and 10, respectively [17]. KOOS JR is a validated 7-item survey assessing knee pain, stiffness, and function in activities of daily living. For scoring, the 5-point Likert scale responses (None, Mild, Moderate, Severe, Extreme) were mapped to ordinal values from 0 to 4, respectively [18,19]. A raw KOOS JR score was calculated as the sum of the 7 items (range: 0–28). Raw scores were transformed to a 0–100 scale using the standard formula where a higher score indicates better function and pain: $$KOOSJR=100-\left(\frac{RawScore\times100}{28}\right)$$ 2.2 Patient follow-up A follow-up electronic survey link was sent 120 days after the cryoneurolysis procedure. Survey data was exported from Qualtrics and processed in Microsoft Excel 2025. Email addresses were used to generate anonymized unique IDs that linked preintervention and postintervention responses from the same participant. 2.3 Cryoneurolysis and Radiofrequency Ablation Technique Cryoneurolysis with Iovera was performed under sterile conditions using ultrasound guidance by Dr. Devin Peck, a fellowship trained anesthesiologist in Austin, Texas. The AFCN, ISN, and LFCN were targeted using cryoneurolysis while the deeper SMGN, SLGN, and IGN were targeted using radiofrequency ablation. 2.4 Statistical analyses Descriptive statistics were calculated for continuous variables (numeric pain scores and KOOS JR scores) at pre- and post-intervention timepoints, including sample size (n), mean, and standard deviation (SD). Due to incomplete follow-up data, two complementary statistical approaches were employed. The primary analysis used paired t-tests to compare pre- and post-intervention scores among patients who completed both assessments (n = 16 pairs), which accounts for within-subject correlation and controls for individual baseline variability. As a secondary analysis, unpaired Welch's t-tests compared all available pre-intervention scores (n = 25) with all available post-intervention scores (n = 16) to maximize use of available data and assess robustness of findings. Welch's t-test was selected over Student's t-test as it does not assume equal variances between groups. For all tests, p < 0.05 was considered statistically significant. All calculations were performed in Excel 2025. Results 3.1 Demographics A total of 25 patients were analyzed in this study. 25 patients completed the pre-procedure survey, and 16 patients completed a 12-week post-procedure survey. All patients with post-procedure data had corresponding baseline responses and were included in the paired analyses. Patient reported outcome variables included subjective numerical rating score of pain (0–10) and functionality scores outlined by validated KOOS JR scores [20,21]. Decreases in pain numerical scores demonstrate improvements and increases in KOOS JR functionality scores demonstrate improvements. Demographic variables included age, sex, and BMI (Table 1). 3.2 Pain In the primary analysis of 16 patients with both pre- and post-intervention pain scores, mean numeric pain decreased from 4.6 ± 2.4 to 1.9 ± 1.6, corresponding to a mean within-patient reduction of 2.5 ± 3.2 points on the 0–10 scale (Table 2). The paired t-test confirmed a statistically significant reduction in pain (t = − 3.14, df = 15, p < 0.05) (Table 3). Using Welch's t-test, this reduction in pain was also statistically significant (t = − 4.27, df = 38.9, p < 0.05) (Table 3). These concordant results indicate a clinically meaningful improvement in knee pain at 120 days following preoperative cryoneurolysis and radiofrequency ablation. 3.3 Functionality (KOOS JR) In the primary analysis of 16 patients with both pre- and post-intervention KOOS JR data, mean KOOS JR (0–100) improved from 49.3 ± 17.8 to 72.3 ± 16.7 (Table 2). The mean within-patient improvement was 26.1 ± 20.6 points. The paired t-test demonstrated a statistically significant improvement in KOOS JR scores (t = 5.08, df = 15, p < 0.05) (Table 4). In the secondary analysis including all available data, mean KOOS JR improved from 49.3 ± 17.8 preintervention (n = 25) to 72.3 ± 16.7 postintervention (n = 16), representing a mean difference of approximately 23.0 points. Using Welch's t-test, KOOS JR scores were significantly higher after preoperative cryoneurolysis and radiofrequency ablation compared with baseline (t = 4.20, df = 33.7, p < 0.05) (Table 4). These findings support a large, clinically meaningful improvement in knee function at 120 days following preoperative cryoneurolysis and radiofrequency ablation before TKA. Table 1 : Patient characteristics of cryoneurolysis treatment group Table 2 : Statistical Analyses Table 3 : Pain NRS t-tests Table 4 : KOOS JR t-tests Discussion This study demonstrates that combining cryoneurolysis and RFA as a preoperative pain management strategy for TKA may offer synergistic benefits for patients. Results demonstrated statistically significant improvements in pain and functionality (Table 2). While both treatment modalities have been shown to offer meaningful reductions in pain and improvements in early functionality, our research demonstrates that their combined integration may leverage the strength of each: cryoneurolysis targeting superficial genicular nerves and RFA for early post op incisional pain and RFA targeting deeper genicular nerves for sustained analgesia lasting several months and improve recovery [5,7–10,16]. Traditionally, postoperative pain management has relied on opioids, nerve blocks, or continuous infusion pumps such as the On-Q pump. Opioids have well known side effects that include post-operative ileus, respiratory depression, and sedation [22]. An additional practical advantage is that the use of cryoneurolysis and RFA reduces or eliminates the need for an On-Q pump, further decreasing medication use, cost, and equipment dependence. These methods could provide pain control through the rehabilitation period and minimize the sharp rise in opioid use observed early in the post-op period, where patients are vulnerable to dependence. From a systemic perspective, this dual modality strategy has potential implications beyond individual patient outcomes as reductions in postoperative pain and opioid use correlates with shorter hospital stays, fewer complications, and lower readmission rates [23]. Considering the growing national burden of healthcare costs and the ongoing opioid crisis, implementing a preoperative dual-modality protocol could represent a scalable and cost-effective option for orthopedic pain management. Regardless, this study has limitations. As an observational study with limited sample size and no control group, broad generalizability is limited. Comorbidities or variations in surgical techniques offer another potential limitation. Furthermore, this study did not have a control group of patients undergoing TKA without preoperative cryoneurolysis and radiofrequency ablation, precluding causal inference and limiting our ability to separate the effects of the intervention from the natural history of disease, placebo effects, or other elements of perioperative care. Additionally, the cryoneurolysis procedure requires a facility with ultrasound which many practitioners do not have. Even with ultrasound, the procedure remains technically challenging. The use of thermal RF for deeper genicular nerves allows for a simpler fluoroscopically guided approach, although ultrasound can also be used. The 3- vs 6-month difference between cryoneurolysis and RFA further adds a secondary advantage while providing sustained articular pain control and significant improvements in functional outcomes [7,16]. The downside is that fluoroscopy cannot be used for cryoneurolysis with iovera with the most commonly used devices. While RFA is effective, the technique on superficial nerves carries risks of thermal injury or transient neuritis, which is typically self-limiting. Conclusion This study highlights the potential of dual modality nerve ablation by combining cryoneurolysis and RFA as an alternative approach to decrease opioid consumption for managing postoperative pain following TKA. This approach safely targets both superficial and deep genicular nerves to provide a comprehensive, sustained analgesia, with improved functional outcomes without the need for continuous infusion pumps. These findings support the growing body of evidence advocating for multimodal motor-sparing pain management techniques in joint replacement surgery. Future randomized control trials with larger patient populations and long term follow up are needed to confirm these results and further refine procedural timing, patient selection, and long-term outcomes. Abbreviations AFCN Anterior Femoral Cutaneous Nerve BMI Body Mass Index IGN Inferomedial Genicular Nerve IRB Institutional Review Board ISN Infrapatellar Branch of the Saphenous Nerve KOOS JR Knee Injury and Osteoarthritis Outcome Score Joint Replacement LFCN Lateral Femoral Cutaneous Nerve NRS Numeric Rating Scale PROMIS Patient-Reported Outcomes Measurement Information System RFA Radiofrequency Ablation SD Standard Deviation SLGN Superior Lateral Genicular Nerve SMGN Superior Medial Genicular Nerve TKA Total Knee Arthroplasty VAS Visual Analog Scale Declarations Conflict of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ethics approval and consent to participate This study involving human participants, human material, and/or human data was conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Declaration of Helsinki and its later amendments. The study was reviewed and approved by the University of Texas Rio Grande Valley Institutional Review Board (IRB-24-0506). Consent to Participate Written informed consent to participate in the study was obtained from all individual participants prior to enrollment. Inclusion criteria for the study were patients older than 18 and English speaking. Consent document can be provided to the journal upon request. Consent for publication Not applicable. Availability of data and materials All data generated or analyzed during this study are included in this published article and its supplementary information files. Competing Interests The authors declare that they have no competing interests Funding This research received no funding. Authors' contributions PB: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Supervision, Visualization, Writing – original draft, Writing – review & editing. Approved the submitted version. Agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature. AM: Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing – original draft. Approved the submitted version. Agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature. JF: Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing – original draft. Approved the submitted version. Agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature. VE: Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing – original draft. Approved the submitted version. Agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature. AA: Supervision. Approved the submitted version. Agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature. DP: Data curation, Writing – review & editing. Approved the submitted version. Agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature. Acknowledgements Not applicable. References Kremers HM, Larson DR, Crowson CS, et al. Prevalence of total hip and knee replacement in the United States. Journal of Bone and Joint Surgery - American Volume . 2014;97(17):1386-1397. doi:10.2106/JBJS.N.01141 Chrysostomides S. Comprehensive Treatment of Knee Osteoarthritis Pain through Cryoneurolysis: A Promising Approach for Deep and Superficial Genicular Nerve Modulation - Case Report. Journal of Orthopaedic Experience & Innovation . 2024;5(1). doi:10.60118/001c.92859 Gaffney CJ, Pelt CE, Gililland JM, Peters CL. Perioperative Pain Management in Hip and Knee Arthroplasty. Orthopedic Clinics of North America . W.B. 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J Arthroplasty . 2018;33(9):2740-2744. doi:10.1016/J.ARTH.2018.04.018 Tables Tables are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Tables.docx v1DeIDENTIFIEDCryoneurolysisDualModality.xlsx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 08 Apr, 2026 Reviewers agreed at journal 02 Apr, 2026 Reviewers invited by journal 01 Apr, 2026 Editor assigned by journal 31 Mar, 2026 Editor invited by journal 03 Mar, 2026 Submission checks completed at journal 02 Mar, 2026 First submitted to journal 02 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8888424","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":617188926,"identity":"de36326f-d1a2-46af-8cef-4069759cf22c","order_by":0,"name":"Paul Bonilla","email":"","orcid":"","institution":"The University of Texas Rio Grande Valley","correspondingAuthor":false,"prefix":"","firstName":"Paul","middleName":"","lastName":"Bonilla","suffix":""},{"id":617188928,"identity":"4f1e4506-b7b7-452b-8fb7-0ee18eefb82c","order_by":1,"name":"Juan Pablo Flanagan","email":"","orcid":"","institution":"Ponce Health Sciences University","correspondingAuthor":false,"prefix":"","firstName":"Juan","middleName":"Pablo","lastName":"Flanagan","suffix":""},{"id":617188929,"identity":"acee76b0-c1a6-40a4-88a6-609ba05bb15c","order_by":2,"name":"Anesu Murambadoro","email":"","orcid":"","institution":"The University of Texas Rio Grande Valley","correspondingAuthor":false,"prefix":"","firstName":"Anesu","middleName":"","lastName":"Murambadoro","suffix":""},{"id":617188933,"identity":"cbf0202f-5fab-4038-9eea-e4ab3be45576","order_by":3,"name":"Victoria Elizondo","email":"","orcid":"","institution":"The University of Texas Rio Grande Valley","correspondingAuthor":false,"prefix":"","firstName":"Victoria","middleName":"","lastName":"Elizondo","suffix":""},{"id":617188944,"identity":"57e4a5e5-e2b7-4b3b-9338-79e840895ac1","order_by":4,"name":"Devin Peck","email":"","orcid":"","institution":"Austin and Georgetown Interventional Pain","correspondingAuthor":false,"prefix":"","firstName":"Devin","middleName":"","lastName":"Peck","suffix":""},{"id":617188945,"identity":"cdb6e198-2b27-4a61-b4d2-0186de1a8bb6","order_by":5,"name":"Aamir Ahmad","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6ElEQVRIiWNgGAWjYJCCA0CcAMSGD2AiEsRqMTYAU8RoYYBqMZMgSgt/++nEwxUMdnm67Ye3VfP+uGe34QDzwds8eLRInMndcPAMQ3Kx2Zm0sts8CcXJGw6wJVvj08JwAKilgYE5cduBHDOgloRkyQYeM2l8WuTPvwVpqU/cdv6NWTFEC/83vFoMboBtOZy47UaOGTNQix0/Aw8bXi2GN0C2GBwHanlWLDknLSGBn5nN2HIOHi1y53M3f2yoqAY6LHnjhzc2CfZs7M0Pb7zB532I8xDMxAZmgsrRgD2pGkbBKBgFo2D4AwDkQVCxLpm2OgAAAABJRU5ErkJggg==","orcid":"","institution":"The University of Texas Rio Grande Valley","correspondingAuthor":true,"prefix":"","firstName":"Aamir","middleName":"","lastName":"Ahmad","suffix":""}],"badges":[],"createdAt":"2026-02-15 21:08:45","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8888424/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8888424/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106311246,"identity":"2e7d05b0-b962-47c5-8596-7efa9b31cd7d","added_by":"auto","created_at":"2026-04-07 10:28:43","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":522553,"visible":true,"origin":"","legend":"\u003cp\u003eTargeted superficial nerves. Reprinted with permission from NYSORA\u003c/p\u003e","description":"","filename":"Figure1.SuperficialNerves.png","url":"https://assets-eu.researchsquare.com/files/rs-8888424/v1/a787832d7d1ccdd621332a8b.png"},{"id":106311257,"identity":"870fe0a8-0cd0-4484-9ebc-0ab6b2cce70e","added_by":"auto","created_at":"2026-04-07 10:28:47","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":185964,"visible":true,"origin":"","legend":"\u003cp\u003eTargeted deep genicular nerves. Reprinted with permission from NYSORA.\u003c/p\u003e","description":"","filename":"Figure2.Deep.png","url":"https://assets-eu.researchsquare.com/files/rs-8888424/v1/3dd0e9547632a9a966f4cee1.png"},{"id":106311249,"identity":"4f4ed558-4fe0-48f7-88c2-28f32f82156f","added_by":"auto","created_at":"2026-04-07 10:28:43","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":326157,"visible":true,"origin":"","legend":"\u003cp\u003eMyelin Sheath and Wallerian Degeneration. Reprinted with permission from Pacira Pharmaceuticals.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8888424/v1/5335be721f37842b8321f120.png"},{"id":106311255,"identity":"6b537215-760e-477f-a000-b261ca271775","added_by":"auto","created_at":"2026-04-07 10:28:46","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":314700,"visible":true,"origin":"","legend":"\u003cp\u003eInsertion of Iovera probe under ultrasound guidance. Reprinted with permission from Pacira Pharmaceuticals.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8888424/v1/1eb1c41b7ca2ed1b20725c1d.png"},{"id":106311300,"identity":"90e8d512-8040-4287-bc52-6136d8c6f52d","added_by":"auto","created_at":"2026-04-07 10:28:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2006991,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8888424/v1/2a2888a7-c285-4dfd-82f0-561065632091.pdf"},{"id":106311247,"identity":"92d5ba9e-e43e-4d1e-9fe5-69920ce63350","added_by":"auto","created_at":"2026-04-07 10:28:43","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":23640,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-8888424/v1/c4dafb50a3cfbf289d6654d7.docx"},{"id":106311267,"identity":"37bb3949-fbaf-4488-899f-e012ad614b30","added_by":"auto","created_at":"2026-04-07 10:28:53","extension":"xlsx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":35079,"visible":true,"origin":"","legend":"","description":"","filename":"v1DeIDENTIFIEDCryoneurolysisDualModality.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8888424/v1/35286044984512c0d72162b3.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Dual-Modality Nerve Ablation: Preoperative Radiofrequency and Cryoneurolysis for Enhanced Pain Relief in Total Knee Arthroplasty","fulltext":[{"header":"Introduction","content":"\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e \u003ch2\u003e1.1 Overview of TKA\u003c/h2\u003e \u003cp\u003eOver 600,000 total knee arthroplasty (TKA) surgeries are performed annually in the United States [1]. This procedure provides significant pain relief for patients suffering from debilitating osteoarthritis or joint degeneration. Surgeons replace damaged articular cartilage with prosthetic components. Although this surgery provides pain relief and increased mobility, challenges persist. Postoperative pain, stiffness, and inflammation can last for weeks, which can negatively impact rehabilitation and recovery. Although there are numerous pain management strategies, reaching a balance between effective analgesia and minimizing adverse effects remains a critical issue. The pain experienced after TKA is multifaceted, arising from both deep articular structures and superficial tissues. Deep genicular nerves, including branches of the femoral, sciatic, and common peroneal nerves, contribute significantly to articular knee pain. Superficial nerves branching from primary contributors to incisional and neuropathic pain. These varied pain sources highlight the need for a comprehensive approach to address multiple nerve targets effectively.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e1.2 Anatomy\u003c/h2\u003e \u003cp\u003eInnervation of the knee includes nerves collectively referred to as the superficial and deep genicular nerves. The superficial genicular nerves are responsible for innervation of the anterior knee. Treatments involving these nerves can improve superficial incisional pain. They include the infrapatellar branch of the saphenous nerve (ISN), the anterior femoral cutaneous nerve (AFCN), and the lateral femoral cutaneous nerve (LFCN) (Fig.\u0026nbsp;1).\u003c/p\u003e \u003cp\u003e \u003cb\u003eFigure 1.\u003c/b\u003e Targeted superficial nerves. Reprinted with permission from NYSORA.\u003c/p\u003e \u003cp\u003eThe deeper genicular nerves include the superior medial genicular nerve (SMGN), terminal branch of the nerve to the vastus medialis which branches off the femoral nerve, superior lateral genicular nerve (SLGN), a direct branch off the sciatic nerve proximal to its bifurcation into the tibial and peroneal nerves, and inferomedial genicular nerve (IGN), a branches off the sciatic nerve [2] (Fig.\u0026nbsp;2).\u003c/p\u003e \u003cp\u003e \u003cb\u003eFigure 2.\u003c/b\u003e Targeted deep genicular nerves. Reprinted with permission from NYSORA.\u003c/p\u003e \u003cp\u003eThese peripheral nerves are surrounded by Schwann cells that aid in sensory signal transduction and promote axonal regeneration. The inevitable pain that comes from surgical incisions and removal of tissue is a result of the activation of pain signals through the transmission of action potentials to the spinal cord and brain [3]. Interventions such as cryoneurolysis and radiofrequency ablation target these peripheral nerves to induce physiological changes such as Wallerian degeneration. In this process, the myelin sheath surrounding an axon breaks down leading to clearance of debris by macrophages [4]. In the weeks to months following injury, Schwann cells are realigned and allow for a growth environment in which axons are regenerated[4].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e1.3 Overview of Cryoneurolysis\u003c/h2\u003e \u003cp\u003eCryoneurolysis involves the induction of Wallerian degeneration through a minimally invasive technique that freezes the peripheral nerves. The Iovera is a handheld device which includes hollow, closed-tip needles used to directly target designated nerves. The handpiece contains a cartridge of liquid nitrous oxide which, when converted into a gas by the device, creates a temperature approaching\u0026thinsp;\u0026minus;\u0026thinsp;87\u0026deg;C at the needles to produce a 5 mm ice ball under the skin. When this ice ball comes in contact with the target nerves, Wallerian degeneration is induced [5]. The cold therapy affects the axon and the myelin sheath but not the endoneurium, allowing for the predictable regrowth of the axon and myelin sheath along the endoneurium [5].\u003c/p\u003e \u003cp\u003e \u003cb\u003eFigure 3.\u003c/b\u003e Myelin Sheath and Wallerian Degeneration. Reprinted with permission from Pacira Pharmaceuticals.\u003c/p\u003e \u003cp\u003eBecause Wallerian degeneration leads to axonal loss by about 36 hours, the procedure is typically done a minimum of 3\u0026ndash;5 days preoperatively. Because repair can take 90 days or more, the procedure is sometimes done several weeks preoperatively [6]. Perioperative cryoneurolysis in combination with standard multimodal pain management has significantly improved outcomes for patients undergoing TKA. With targeting the ISN and AFCN, patients have exhibited markedly reduced PROMIS pain intensity scores at two-week post-surgery, shorter hospital stays and significantly less knee symptoms [5]. These specific nerves have been chosen because they lie in predictable locations allowing for effective targeting with the cryoneurolysis procedure. Because this procedure is primarily done on sensory-only superficial genicular nerves, motor function is preserved [5].\u003c/p\u003e \u003cp\u003e \u003cb\u003eFigure 4.\u003c/b\u003e Insertion of Iovera probe under ultrasound guidance. Reprinted with permission from Pacira Pharmaceuticals.\u003c/p\u003e \u003cp\u003eThis detail is crucially important as patients require motor preservation for their rehabilitation. On average, cryoneurolysis results in an average pain relief duration of 3 months [7].\u003c/p\u003e \u003cp\u003eClinical studies have demonstrated its effectiveness in reducing opioid consumption and pain scores postoperatively [5,8,9]. A retrospective review of patients who underwent preoperative cryoneurolysis revealed a 35% reduction in opioid use at two weeks and a 36% reduction at six weeks, alongside notable improvements in reported pain scores [10]. However, in this study, patients treated perioperatively with cryoneurolysis required opioid refills at two-week postoperative marks, likely due to receiving lower total morphine milligram equivalents. Despite this, a pronounced tapering of opioid use was observed at the six-week mark, demonstrating a reduced risk of long-term opioid dependence. This finding highlights the need for strategies that can enhance early pain-relief effects of cryoneurolysis while maintaining benefits in minimizing opioid consumption over time such as improved targeting of all nerves that contribute to postoperative knee pain.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e1.4 Overview of Radiofrequency Ablation\u003c/h2\u003e \u003cp\u003eRadiofrequency ablation (RFA) has been used to treat chronic pain, including back pain, for decades and is a well-established pain management technique. This ablation method utilizes a specialized probe to deliver heat through electrical currents to ablate sensory nerves [11]. The goal temperature of this method ranges from 60\u0026deg;C\u0026thinsp;\u0026minus;\u0026thinsp;90\u0026deg;C [12]. The technique begins with placement of a thin, insulated needle (cannula) equipped with an electrode at its tip which is guided to the target nerve utilizing imaging guidance. The heat generated creates a lesion in nerve tissue, effectively disrupting the ability to transmit pain signals. At typical temperatures and durations, such as 80\u0026deg; C for 90 seconds, connective-tissue layers such as the endoneurium, perineurium and epineurium are left largely intact. This allows for the repair of neural tissue along a predictable pathway and reduces the risk of neuroma formation. Radiofrequency ablation is primarily used to target deeper genicular nerves instead of superficial genicular nerves due to the risk of a burn injury to the skin. Targeting deep nerves is important because superficial nerves may not be the primary source of pain, while targeting deeper nerves more involved in pain pathways can provide more effective and lasting relief [13]. Studies have highlighted the efficacy of RFA in treating knee osteoarthritis pain, which is usually done under fluoroscopy or ultrasound guide [13]. Patients treated with RFA have reported significant reduction in pain, as measured by Visual Analog Scale (VAS) scores, and improvements in functional outcomes [13\u0026ndash;15].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e1.5 Combination Technique\u003c/h2\u003e \u003cp\u003eA dual-modality approach of cryoneurolysis and radiofrequency ablation offers an innovative approach to managing preoperative pain in patients undergoing total knee arthroplasty. Through this method, superficial genicular nerves can be targeted through cryoneurolysis and deeper genicular nerves can be targeted using radiofrequency ablation. Cryoneurolysis offers rapid pain relief lasting 3 months whereas radiofrequency ablation has been shown to offer significant pain relief for 6 months or longer in patients with chronic knee pain [7,16]. The integration of these two techniques capitalizes on their respective strengths and facilitates an effective postoperative pain management strategy: reduced pain, decreased opioid consumption, improved range of motion for better rehabilitation. These techniques have been traditionally employed for relief of knee pain in patients that are refractory to conservative care such as nonsteroidal anti-inflammatory use or steroid injections and who are not candidates for joint replacement or wish to defer such surgery. More recently, these techniques have been used for adjunctive relief of post-operative pain following total knee replacement [9]. This combination can reduce the need for post-operative opioids, which may be a primary goal for some patients who do not tolerate such medications. While some orthopedic surgeons may express hesitancy towards a percutaneous technique within days or weeks of surgery, key aspects of the procedure can allay any infection-control or other concerns. In particular, it is important to note that these nerves are targeted entirely in extra-articular locations, and that no steroid is required.\u003c/p\u003e \u003c/div\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study Design\u003c/h2\u003e \u003cp\u003eA prospective observational cohort study of patients undergoing cryoneurolysis and radiofrequency ablation as part of preoperative management before TKA between March 2025 and December 2025 was performed at a single outpatient practice. All information was collected from patients undergoing standard of care TKA by a fellowship trained orthopedic surgeon in Austin, Texas. The study was approved by The University of Texas Rio Grande Valley School of Medicine Institutional Review Board (IRB-24-0506). Inclusion criteria included patients over 18 years old who were able to read and understand English. Prior to their cryoneurolysis procedure, eligible patients were invited to participate by scanning a QR code displayed at check-in. Participation was entirely voluntary and had no impact on access to care, the decision to perform cryoneurolysis/RFA or TKA, or any aspect of perioperative management. Patients who completed the baseline survey on the day of the procedure, prior to cryoneurolysis, were enrolled in the study cohort.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Outcomes\u003c/h2\u003e \u003cp\u003eThe QR code directed patients to a Qualtrics survey where patients rated their current knee pain on an 11-point numeric rating scale (NRS) from 0 to 10, where 0 = \u0026ldquo;No pain\u0026rdquo; and 10 = \u0026ldquo;Worst pain possible.\u0026rdquo; Responses such as \u0026ldquo;0 \u0026ndash; No Pain\u0026rdquo; and \u0026ldquo;10 \u0026ndash; Worst Pain Possible\u0026rdquo; were coded to numeric values 0 and 10, respectively [17]. KOOS JR is a validated 7-item survey assessing knee pain, stiffness, and function in activities of daily living. For scoring, the 5-point Likert scale responses (None, Mild, Moderate, Severe, Extreme) were mapped to ordinal values from 0 to 4, respectively [18,19]. A raw KOOS JR score was calculated as the sum of the 7 items (range: 0\u0026ndash;28). Raw scores were transformed to a 0\u0026ndash;100 scale using the standard formula where a higher score indicates better function and pain:\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$KOOSJR=100-\\left(\\frac{RawScore\\times100}{28}\\right)$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Patient follow-up\u003c/h2\u003e \u003cp\u003eA follow-up electronic survey link was sent 120 days after the cryoneurolysis procedure. Survey data was exported from Qualtrics and processed in Microsoft Excel 2025. Email addresses were used to generate anonymized unique IDs that linked preintervention and postintervention responses from the same participant.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Cryoneurolysis and Radiofrequency Ablation Technique\u003c/h2\u003e \u003cp\u003eCryoneurolysis with Iovera was performed under sterile conditions using ultrasound guidance by Dr. Devin Peck, a fellowship trained anesthesiologist in Austin, Texas. The AFCN, ISN, and LFCN were targeted using cryoneurolysis while the deeper SMGN, SLGN, and IGN were targeted using radiofrequency ablation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Statistical analyses\u003c/h2\u003e \u003cp\u003eDescriptive statistics were calculated for continuous variables (numeric pain scores and KOOS JR scores) at pre- and post-intervention timepoints, including sample size (n), mean, and standard deviation (SD). Due to incomplete follow-up data, two complementary statistical approaches were employed. The primary analysis used paired t-tests to compare pre- and post-intervention scores among patients who completed both assessments (n\u0026thinsp;=\u0026thinsp;16 pairs), which accounts for within-subject correlation and controls for individual baseline variability. As a secondary analysis, unpaired Welch's t-tests compared all available pre-intervention scores (n\u0026thinsp;=\u0026thinsp;25) with all available post-intervention scores (n\u0026thinsp;=\u0026thinsp;16) to maximize use of available data and assess robustness of findings. Welch's t-test was selected over Student's t-test as it does not assume equal variances between groups. For all tests, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. All calculations were performed in Excel 2025.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Demographics\u003c/h2\u003e \u003cp\u003eA total of 25 patients were analyzed in this study. 25 patients completed the pre-procedure survey, and 16 patients completed a 12-week post-procedure survey. All patients with post-procedure data had corresponding baseline responses and were included in the paired analyses. Patient reported outcome variables included subjective numerical rating score of pain (0\u0026ndash;10) and functionality scores outlined by validated KOOS JR scores [20,21]. Decreases in pain numerical scores demonstrate improvements and increases in KOOS JR functionality scores demonstrate improvements. Demographic variables included age, sex, and BMI (Table\u0026nbsp;1).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Pain\u003c/h2\u003e \u003cp\u003eIn the primary analysis of 16 patients with both pre- and post-intervention pain scores, mean numeric pain decreased from 4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4 to 1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6, corresponding to a mean within-patient reduction of 2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2 points on the 0\u0026ndash;10 scale (Table\u0026nbsp;2). The paired t-test confirmed a statistically significant reduction in pain (t\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;3.14, df\u0026thinsp;=\u0026thinsp;15, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;3). Using Welch's t-test, this reduction in pain was also statistically significant (t\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;4.27, df\u0026thinsp;=\u0026thinsp;38.9, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;3). These concordant results indicate a clinically meaningful improvement in knee pain at 120 days following preoperative cryoneurolysis and radiofrequency ablation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Functionality (KOOS JR)\u003c/h2\u003e \u003cp\u003eIn the primary analysis of 16 patients with both pre- and post-intervention KOOS JR data, mean KOOS JR (0\u0026ndash;100) improved from 49.3\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8 to 72.3\u0026thinsp;\u0026plusmn;\u0026thinsp;16.7 (Table\u0026nbsp;2). The mean within-patient improvement was 26.1\u0026thinsp;\u0026plusmn;\u0026thinsp;20.6 points. The paired t-test demonstrated a statistically significant improvement in KOOS JR scores (t\u0026thinsp;=\u0026thinsp;5.08, df\u0026thinsp;=\u0026thinsp;15, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;4). In the secondary analysis including all available data, mean KOOS JR improved from 49.3\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8 preintervention (n\u0026thinsp;=\u0026thinsp;25) to 72.3\u0026thinsp;\u0026plusmn;\u0026thinsp;16.7 postintervention (n\u0026thinsp;=\u0026thinsp;16), representing a mean difference of approximately 23.0 points. Using Welch's t-test, KOOS JR scores were significantly higher after preoperative cryoneurolysis and radiofrequency ablation compared with baseline (t\u0026thinsp;=\u0026thinsp;4.20, df\u0026thinsp;=\u0026thinsp;33.7, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;4). These findings support a large, clinically meaningful improvement in knee function at 120 days following preoperative cryoneurolysis and radiofrequency ablation before TKA.\u003c/p\u003e \u003cp\u003e \u003cb\u003eTable\u0026nbsp;1\u003c/b\u003e:\u003c/p\u003e \u003cp\u003ePatient characteristics of cryoneurolysis treatment group\u003c/p\u003e \u003cp\u003e \u003cb\u003eTable\u0026nbsp;2\u003c/b\u003e:\u003c/p\u003e \u003cp\u003eStatistical Analyses\u003c/p\u003e \u003cp\u003e \u003cb\u003eTable\u0026nbsp;3\u003c/b\u003e:\u003c/p\u003e \u003cp\u003ePain NRS t-tests\u003c/p\u003e \u003cp\u003e \u003cb\u003eTable\u0026nbsp;4\u003c/b\u003e:\u003c/p\u003e \u003cp\u003eKOOS JR t-tests\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrates that combining cryoneurolysis and RFA as a preoperative pain management strategy for TKA may offer synergistic benefits for patients. Results demonstrated statistically significant improvements in pain and functionality (Table\u0026nbsp;2). While both treatment modalities have been shown to offer meaningful reductions in pain and improvements in early functionality, our research demonstrates that their combined integration may leverage the strength of each: cryoneurolysis targeting superficial genicular nerves and RFA for early post op incisional pain and RFA targeting deeper genicular nerves for sustained analgesia lasting several months and improve recovery [5,7\u0026ndash;10,16].\u003c/p\u003e \u003cp\u003eTraditionally, postoperative pain management has relied on opioids, nerve blocks, or continuous infusion pumps such as the On-Q pump. Opioids have well known side effects that include post-operative ileus, respiratory depression, and sedation [22]. An additional practical advantage is that the use of cryoneurolysis and RFA reduces or eliminates the need for an On-Q pump, further decreasing medication use, cost, and equipment dependence. These methods could provide pain control through the rehabilitation period and minimize the sharp rise in opioid use observed early in the post-op period, where patients are vulnerable to dependence.\u003c/p\u003e \u003cp\u003eFrom a systemic perspective, this dual modality strategy has potential implications beyond individual patient outcomes as reductions in postoperative pain and opioid use correlates with shorter hospital stays, fewer complications, and lower readmission rates [23]. Considering the growing national burden of healthcare costs and the ongoing opioid crisis, implementing a preoperative dual-modality protocol could represent a scalable and cost-effective option for orthopedic pain management.\u003c/p\u003e \u003cp\u003eRegardless, this study has limitations. As an observational study with limited sample size and no control group, broad generalizability is limited. Comorbidities or variations in surgical techniques offer another potential limitation. Furthermore, this study did not have a control group of patients undergoing TKA without preoperative cryoneurolysis and radiofrequency ablation, precluding causal inference and limiting our ability to separate the effects of the intervention from the natural history of disease, placebo effects, or other elements of perioperative care. Additionally, the cryoneurolysis procedure requires a facility with ultrasound which many practitioners do not have. Even with ultrasound, the procedure remains technically challenging. The use of thermal RF for deeper genicular nerves allows for a simpler fluoroscopically guided approach, although ultrasound can also be used. The 3- vs 6-month difference between cryoneurolysis and RFA further adds a secondary advantage while providing sustained articular pain control and significant improvements in functional outcomes [7,16]. The downside is that fluoroscopy cannot be used for cryoneurolysis with iovera with the most commonly used devices. While RFA is effective, the technique on superficial nerves carries risks of thermal injury or transient neuritis, which is typically self-limiting.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study highlights the potential of dual modality nerve ablation by combining cryoneurolysis and RFA as an alternative approach to decrease opioid consumption for managing postoperative pain following TKA. This approach safely targets both superficial and deep genicular nerves to provide a comprehensive, sustained analgesia, with improved functional outcomes without the need for continuous infusion pumps. These findings support the growing body of evidence advocating for multimodal motor-sparing pain management techniques in joint replacement surgery. Future randomized control trials with larger patient populations and long term follow up are needed to confirm these results and further refine procedural timing, patient selection, and long-term outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAFCN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAnterior Femoral Cutaneous Nerve\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBody Mass Index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIGN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInferomedial Genicular Nerve\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIRB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInstitutional Review Board\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eISN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInfrapatellar Branch of the Saphenous Nerve\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eKOOS JR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eKnee Injury and Osteoarthritis Outcome Score Joint Replacement\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLFCN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLateral Femoral Cutaneous Nerve\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNRS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNumeric Rating Scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePROMIS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePatient-Reported Outcomes Measurement Information System\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRFA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRadiofrequency Ablation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStandard Deviation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSLGN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSuperior Lateral Genicular Nerve\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSMGN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSuperior Medial Genicular Nerve\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTKA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTotal Knee Arthroplasty\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVAS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVisual Analog Scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003eThe authors declare the following financial interests/personal relationships which may be considered as potential competing interests:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study involving human participants, human material, and/or human data was conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Declaration of Helsinki and its later amendments. The study was reviewed and approved by the University of Texas Rio Grande Valley Institutional Review Board (IRB-24-0506).\u003c/p\u003e\n\n\u003cp\u003eConsent to Participate\u003c/p\u003e\n\u003cp\u003eWritten informed consent to participate in the study was obtained from all individual participants prior to enrollment. Inclusion criteria for the study were patients older than 18 and English speaking. Consent document can be provided to the journal upon request.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article and its supplementary information files.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no funding.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePB: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Supervision, Visualization, Writing \u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing. Approved the submitted version. Agreed both to be personally accountable for the author\u0026apos;s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.\u003c/p\u003e\n\n\u003cp\u003eAM: Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing \u0026ndash; original draft. Approved the submitted version. Agreed both to be personally accountable for the author\u0026apos;s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.\u003c/p\u003e\n\n\u003cp\u003eJF: Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing \u0026ndash; original draft. Approved the submitted version. Agreed both to be personally accountable for the author\u0026apos;s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.\u003c/p\u003e\n\n\u003cp\u003eVE: Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing \u0026ndash; original draft. Approved the submitted version. Agreed both to be personally accountable for the author\u0026apos;s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.\u003c/p\u003e\n\n\u003cp\u003eAA: Supervision. Approved the submitted version. Agreed both to be personally accountable for the author\u0026apos;s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.\u003c/p\u003e\n\n\u003cp\u003eDP: Data curation, Writing \u0026ndash; review \u0026amp; editing. Approved the submitted version. Agreed both to be personally accountable for the author\u0026apos;s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\n\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKremers HM, Larson DR, Crowson CS, et al. Prevalence of total hip and knee replacement in the United States. \u003cem\u003eJournal of Bone and Joint Surgery - American Volume\u003c/em\u003e. 2014;97(17):1386-1397. doi:10.2106/JBJS.N.01141\u003c/li\u003e\n\u003cli\u003eChrysostomides S. Comprehensive Treatment of Knee Osteoarthritis Pain through Cryoneurolysis: A Promising Approach for Deep and Superficial Genicular Nerve Modulation - Case Report. \u003cem\u003eJournal of Orthopaedic Experience \u0026amp; Innovation\u003c/em\u003e. 2024;5(1). doi:10.60118/001c.92859\u003c/li\u003e\n\u003cli\u003eGaffney CJ, Pelt CE, Gililland JM, Peters CL. Perioperative Pain Management in Hip and Knee Arthroplasty. \u003cem\u003eOrthopedic Clinics of North America\u003c/em\u003e. \u003cem\u003eW.B. Saunders\u003c/em\u003e. 2017;48(4):407-419. doi:10.1016/j.ocl.2017.05.001\u003c/li\u003e\n\u003cli\u003eGaudet AD, Popovich PG, Ramer MS. Wallerian degeneration: Gaining perspective on inflammatory events after peripheral nerve injury. \u003cem\u003eJ Neuroinflammation\u003c/em\u003e. 2011;8. doi:10.1186/1742-2094-8-110\u003c/li\u003e\n\u003cli\u003eDasa V, Lensing G, Parsons M, Harris J, Volaufova J, Bliss R. Percutaneous freezing of sensory nerves prior to total knee arthroplasty. \u003cem\u003eKnee\u003c/em\u003e. 2016;23(3):523-528. doi:10.1016/j.knee.2016.01.011\u003c/li\u003e\n\u003cli\u003eRotshenker S. Wallerian degeneration: The innate-immune response to traumatic nerve injury. \u003cem\u003eJ Neuroinflammation\u003c/em\u003e. 2011;8. doi:10.1186/1742-2094-8-109\u003c/li\u003e\n\u003cli\u003eRadnovich R, Scott D, Patel AT, et al. Cryoneurolysis to treat the pain and symptoms of knee osteoarthritis: a multicenter, randomized, double-blind, sham-controlled trial. \u003cem\u003eOsteoarthritis Cartilage\u003c/em\u003e. 2017;25(8):1247-1256. doi:10.1016/j.joca.2017.03.006\u003c/li\u003e\n\u003cli\u003eMihalko WM, Kerkhof AL, Ford MC, Crockarell JR, Harkess JW, Guyton JL. Cryoneurolysis before Total Knee Arthroplasty in Patients With Severe Osteoarthritis for Reduction of Postoperative Pain and Opioid Use in a Single-Center Randomized Controlled Trial. In: \u003cem\u003eJournal of Arthroplasty\u003c/em\u003e. Vol 36. Elsevier B.V.; 2021:1590-1598. doi:10.1016/j.arth.2020.11.013\u003c/li\u003e\n\u003cli\u003eMont MA, Lin JH, Spitzer AI, et al. Cryoneurolysis Associated With Improved Pain, Function, and Sleep in Patients Following total Knee Arthroplasty: Use of a New Real-World Registry. \u003cem\u003eJournal of Arthroplasty\u003c/em\u003e. Published online 2024. doi:10.1016/j.arth.2024.06.054\u003c/li\u003e\n\u003cli\u003eUrban JA, Dolesh K, Martin E. A Multimodal Pain Management Protocol Including Preoperative Cryoneurolysis for Total Knee Arthroplasty to Reduce Pain, Opioid Consumption, and Length of Stay. \u003cem\u003eArthroplast Today\u003c/em\u003e. 2021;10:87-92. doi:10.1016/j.artd.2021.06.008\u003c/li\u003e\n\u003cli\u003eIkeuchi M, Ushida T, Izumi M, Tani T. \u003cem\u003ePercutaneous Radiofrequency Treatment for Refractory Anteromedial Pain of Osteoarthritic Kneesp Me_1086 546..551\u003c/em\u003e. https://academic.oup.com/painmedicine/article/12/4/546/1868158\u003c/li\u003e\n\u003cli\u003eLee L, Epelboym Y. Review of genicular artery embolization, radiofrequency ablation, and cryoneurolysis in the management of osteoarthritis-related knee pain. \u003cem\u003eDiagnostic and Interventional Radiology\u003c/em\u003e. \u003cem\u003eGalenos Publishing House\u003c/em\u003e. 2023;29(4):614-620. doi:10.4274/dir.2022.221288\u003c/li\u003e\n\u003cli\u003eChoi WJ, Hwang SJ, Song JG, et al. Radiofrequency treatment relieves chronic knee osteoarthritis pain: A double-blind randomized controlled trial. \u003cem\u003ePain\u003c/em\u003e. 2011;152(3):481-487. doi:10.1016/j.pain.2010.09.029\u003c/li\u003e\n\u003cli\u003eEH EH, Elawamy A, EZ K, et al. Fluoroscopic Guided Radiofrequency of Genicular Nerves for Pain Alleviation in Chronic Knee Osteoarthritis: a Single-Blind Randomized Controlled Trial. \u003cem\u003ePain Physician\u003c/em\u003e. 2018;21(2).\u003c/li\u003e\n\u003cli\u003eConger A, Gililland J, Anderson L, Pelt CE, Peters C, Mccormick ZL. Genicular Nerve Radiofrequency Ablation for the Treatment of Painful Knee Osteoarthritis: Current Evidence and Future Directions. \u003cem\u003ePain Medicine (United States)\u003c/em\u003e. 2021;22. doi:10.1093/pm/pnab129\u003c/li\u003e\n\u003cli\u003eChen AF, Mullen K, Casambre F, Visvabharathy V, Brown GA. Thermal Nerve Radiofrequency Ablation for the Nonsurgical Treatment of Knee Osteoarthritis: A Systematic Literature Review. \u003cem\u003eJournal of the American Academy of Orthopaedic Surgeons\u003c/em\u003e. 2021;29(9):387-396. doi:10.5435/JAAOS-D-20-00522\u003c/li\u003e\n\u003cli\u003eAlghadir AH, Anwer S, Iqbal A, Iqbal ZA. Test-retest reliability, validity, and minimum detectable change of visual analog, numerical rating, and verbal rating scales for measurement of osteoarthritic knee pain. \u003cem\u003eJ Pain Res\u003c/em\u003e. 2018;11:851-856. doi:10.2147/JPR.S158847\u003c/li\u003e\n\u003cli\u003eRoos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD. \u003cem\u003eKnee Injury and Osteoarthritis Outcome Score (~00~)-Development of a Self-Administered Outcome Measure\u003c/em\u003e. Vol 78. 2026. www.jospt.org\u003c/li\u003e\n\u003cli\u003eLyman S, Lee YY, Franklin PD, Li W, Cross MB, Padgett DE. Validation of the KOOS, JR: A Short-form Knee Arthroplasty Outcomes Survey. \u003cem\u003eClin Orthop Relat Res\u003c/em\u003e. 2016;474(6):1461-1471. doi:10.1007/s11999-016-4719-1\u003c/li\u003e\n\u003cli\u003eAlghadir AH, Anwer S, Iqbal A, Iqbal ZA. Test-retest reliability, validity, and minimum detectable change of visual analog, numerical rating, and verbal rating scales for measurement of osteoarthritic knee pain. \u003cem\u003eJ Pain Res\u003c/em\u003e. 2018;11. doi:10.2147/JPR.S158847\u003c/li\u003e\n\u003cli\u003eLyman S, Lee YY, Franklin PD, Li W, Cross MB, Padgett DE. Validation of the KOOS, JR: A Short-form Knee Arthroplasty Outcomes Survey. \u003cem\u003eClin Orthop Relat Res\u003c/em\u003e. 2016;474(6). doi:10.1007/s11999-016-4719-1\u003c/li\u003e\n\u003cli\u003eDaigle C, Branstetter IV R, Van Deventer L, et al. In-Hospital Exposure and Opioids Prescribed After Total Knee Arthroplasty. \u003cem\u003eJ Arthroplasty\u003c/em\u003e. Published online September 2025. doi:10.1016/j.arth.2025.09.011\u003c/li\u003e\n\u003cli\u003eSchroer WC, Diesfeld PJ, LeMarr AR, Morton DJ, Reedy ME. Modifiable Risk Factors in Primary Joint Arthroplasty Increase 90-Day Cost of Care. \u003cem\u003eJ Arthroplasty\u003c/em\u003e. 2018;33(9):2740-2744. doi:10.1016/J.ARTH.2018.04.018 \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables are available in the Supplementary Files section.\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8888424/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8888424/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePost-operative pain management following total knee arthroplasty often fall short in addressing deep and superficial pain sources effectively. Cryoneurolysis and radiofrequency ablation (RFA) are established techniques that induce Wallerian degeneration to disrupt pain pathways but are rarely used in tandem. This study aims to investigate a novel dual-modality preoperative pain management technique combining RFA and cryoneurolysis to improve patient outcomes and reduce opioid dependence postoperatively.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA prospective observational study was performed on patients undergoing cryoneurolysis and radiofrequency ablation before primary TKA from March 2025 \u0026ndash; December 2025. Primary outcome measures were obtained through surveys investigating pain through numerical rating scores (0\u0026ndash;10) and functionality through Knee Injury and Osteoarthritis Outcome Score Joint Replacement (KOOS JR) scores. All information was collected from patients undergoing standard of care TKA. Pre-operative data was obtained during the first cryoneurolysis and radiofrequency ablation visit while post-operative data was electronically through Qualtrics 12 weeks post cryoneurolysis and radiofrequency ablation.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e25 patients completed baseline surveys and 16 provided 120-day post-procedure data. Mean numeric pain scores decreased from 4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4 to 1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6 (p\u0026thinsp;=\u0026thinsp;0.0001); in the 16 patients with paired data, pain decreased by 2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2 points (paired t\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;3.14, p\u0026thinsp;=\u0026thinsp;0.007). KOOS JR scores improved from 49.3\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8 to 72.3\u0026thinsp;\u0026plusmn;\u0026thinsp;16.7 (p\u0026thinsp;=\u0026thinsp;0.0002); among paired patients, KOOS JR increased by 26.1\u0026thinsp;\u0026plusmn;\u0026thinsp;20.6 points (paired t\u0026thinsp;=\u0026thinsp;5.08, p\u0026thinsp;=\u0026thinsp;0.0001). These findings demonstrate large, statistically and clinically significant improvements in knee pain and function 120 days after preoperative cryoneurolysis and radiofrequency ablation.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe integration of these two individually successful techniques capitalizes on their respective strengths and facilitates an effective postoperative pain management strategy: reduced pain, decreased opioid consumption, and increased range of motion. The implementation of this dual approach offers significant progress in orthopedics and pain management while addressing the opioid epidemic and rising healthcare costs that come with longer hospital stays and complications. Further research is warranted to investigate long-term efficacy.\u003c/p\u003e","manuscriptTitle":"Dual-Modality Nerve Ablation: Preoperative Radiofrequency and Cryoneurolysis for Enhanced Pain Relief in Total Knee Arthroplasty","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-07 10:27:37","doi":"10.21203/rs.3.rs-8888424/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"151487099551643965062199817468416502160","date":"2026-04-08T14:00:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"199759422543569329710634852186786484213","date":"2026-04-02T15:57:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-01T15:01:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-31T08:37:58+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-03T05:23:22+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-03T02:57:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Musculoskeletal Disorders","date":"2026-03-03T01:08:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ef6a3336-1038-4d69-8e24-a8ac45362507","owner":[],"postedDate":"April 7th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-07T10:27:38+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-07 10:27:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8888424","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8888424","identity":"rs-8888424","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}