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Introduction:
Cryoneurolysis is the direct application of low temperatures to reversibly kill peripheral nerves to provide pain relief. Recent development of a handheld cryoneurolysis device with small gauge needles and an integrated skin warmer broadens the clinical applications to include treatment of superficial nerves, further enabling treatme...
Contexts in source publication
Context 1
... nerves allow communication between the spinal cord and the tissues/organs of the body. The innermost part of the nerve is the axon, which conducts signals between the brain and tissues (Figure 1). In myelinated nerves, these axons are surrounded by a myelin sheath composed of concentric layers of Schwann cells which function to increase neuronal signaling speeds. ...
Context 2
... covering is concentrically laminated with flattened perineurial cells, basement mem- branes, and collagen fibers. Epineurium, a layer of dense con- nective tissue, covers and holds together these bundles to create the outer surface of nerves ( Figure 1). published a 3-point nerve injury scale in 1943 [4], and in 1951, Sir Sydney Sunderland published a 5-point scale which gave more resolution to Seddon's scale (Table 1) [5]. ...
Citations
... Generally, cryoneurolysis is performed via a 20-gauge, 90mm closed-end needle or three 27-gauge, 8mm closed-end needles. 21 This allows exposure of the appropriate nerve to low temperatures, achieved via cryogen (nitrous oxide) flow from the cartridge to the closed-end SmartTip ® (Pacira Cryotech, Inc., in Fremont, California). 22,23 In aggregate, a total of 502 patients who had symptomatic unilateral knee OA were identified between September 21, 2021, and February 1, 2024, with at least 30 days and up to three years of follow up. ...
Introduction:
There is a wide range of nonoperative options to manage symptomatic knee osteoarthritis (OA). This paper aimed to 1) define the treatment sequence for patients undergoing up to four subsequent rounds (i.e., cryoneurolysis) of superficial (Cryo-Superficial) and/or deep genicular nerves (Cryo-Deep/Both), intra-articular corticosteroid injections (IA-CS), triamcinolone extended-release (IA-TA-ER), hyaluronic acid (IA-HA), or non-steroidal anti-inflammatory drugs (IA-NSAIDs); 2) compare usage of extended-release versus standard corticosteroid injections; and 3) quantify distribution of repeated treatments.
Materials and methods:
We identified 502 patients with symptomatic knee OA and received nonoperative intervention within the Innovations in Genicular Outcomes (IGOR) registry from 2021 to 2024. Treatment journey during follow up was presented aggregating baseline patient demographics, along with sequence of nonoperative treatments per patient, duration, and frequency of repeated use. Repeated use of Round 1 treatment for subsequent treatment rounds was estimated with descriptive statistics.
Results:
Fifty-three percent of patients received only the original Round 1 treatment option, either single/repeated dose and did not receive any alternative treatment. Seventy-three percent of patients treated with intra-articular extended-release triamcinolone (IA-TAER) repeated the treatment at least once, whereas 60% of those treated with other treatments did so. No adverse events were reported in patients during repeated treatments.
Conclusion:
Patients who received IA-TAER were more likely to repeat the same injection, with 73% repeating at least once and no adverse events were attributed to repeated injections. Approximately half of the patients have switched from the initial treatment offered during follow up, with the use of IA-TAER associated with higher rates of repeated treatment. Significance and Innovation 1. Our study used a newly developed real-world registry IGOR to characterize treatment progression for patients with symptomatic knee OA undergoing up to five rounds of nonoperative treatment. 2. Non-surgical interventions included cryoneurolysis, intra-articular injections of NSAIDs, hyaluronic acid injections, corticosteroid, or extended release steroid (triamcinolone) injections. 3. We found 73% of patients treated with intra-articular extended-release steroid injections repeated treatment at least once, relative to 60% by other treatments. 4. We found approximately half of patients switched from initial treatment offered during follow up, with the use of IA-TAER associated with higher rates of repeated treatment.
... Te tip of the cryoprobe is then positioned adjacent to a target nerve. At initiation of treatment, a gas, such as nitrous oxide, carbon dioxide, or argon, travels down the center of the probe, where it escapes through a small opening, which causes a Joule-Tomson efect-a thermodynamic principle that describes how a gas temperature changes when it expands [7]. Te temperature cools as the gas expands, which subsequently creates the ice ball. ...
Slipping rib syndrome (SRS) is an underdiagnosed condition, in which some ribs are not connected to the sternum, which may cause increased laxity of the interchondral ligament. This may result in pain in the lower chest and upper abdomen area. Treatment typically includes conservative measures, steroid injections, and surgery. Ultrasound-guided intercostal cryoneurolysis is a minimally-invasive procedure that may provide long-term analgesia in patients with SRS. This case report describes the procedure for a patient treated with right-sided ultrasound-guided cryoneurolysis of the intercostal nerves at the levels T7, T8, and T9.
... These techniques initially required surgical incisions to access target nerves, which limited their use to specific procedures like thoracotomies, tonsillectomies, and herniorrhaphies [11]. However, with the development of percutaneous techniques, the requirement for surgery vanished, and the integration of imaging technologies such as ultrasound, CT, and MRI broadened the scope of cryoneurolysis applications [6]. ...
... Overall, this opened up many possibilities in acute and chronic pain management. Figure 1 depicts the historic evolution of cryoneurolysis in pain management [6,7,[9][10][11][12]. ...
... Mylavarapu, M. (2025) https://BioRender.com/y55z016; Sources: [6,7,[9][10][11][12] (2 Hz) responses. An introducer is recommended for optimal efficacy, as it isolates current at the probe tip, protects skin during treatments, and facilitates anesthetic infiltration for nerve blockage using fluoroscopy, ultrasonography, and nerve stimulators [1]. ...
... Recent advances in sensory peripheral nerve blocks have enabled targeted anesthesia of superficial sensory nerves without causing motor blockades. This technique offers advantages such as faster rehabilitation, early recovery, and a lower risk of postoperative accidental falls compared to femoral nerve blocks [10,11]. ...
Blocking the infrapatellar branch of the saphenous nerve (IPBSN) can provide analgesic benefits for patients with postoperative acute pain or chronic pain, with minimal adverse effects. To evaluate the analgesic efficacy and potential adverse events associated with IPBSN block in patients suffering from acute or chronic knee pain. We conducted a systematic review across PubMed, Cochrane, Web of Science, and Embase to identify all relevant randomized controlled trials (RCTs) and cohort studies according to predefined selection criteria. The study quality of the RCTs was evaluated using the Cochrane risk of bias assessment tool, while cohort studies were assessed using the ROBINS‐I risk of bias tool. The primary outcomes measured were pain intensity and opioid consumption following the nerve block. A total of eight studies were included in this systematic review, encompassing 613 subjects with 276 participants in the control group and 337 participants in the IPBSN block group. The level of evidence was rated high for the RCTs and moderate for the cohort studies. The nerve block was administrated either through the injection of local anesthetic or percutaneous cryoneurolysis targeting the IPBSN. The results indicated that the IPBSN block significantly improved pain relief and reduced opioid consumption in patients with acute postoperative or chronic pain, with no significant difference in the rate of adverse events relating to the procedures or device. The IPBSN block holds promise for improving pain relief and reducing opioid consumption. However, further well‐designed randomized controlled trials are needed to confirm these results.
... This leads to reversible partial nerve ablation due to Wallerian degeneration (degeneration of axon and myelin sheath) and nerve regeneration. 38 Cryoneurolysis may therefore have an advantage over phenol and alcohol, which causes damage to surrounding tissues and decreases the ability to use it over time. In addition, cryoneurolysis does not damage the basal lamina, epineurium, and perineurium of the targeted nerve and serves as a conduit for neural regeneration. ...
Cerebral Palsy (CP) encompasses a spectrum of permanent motor disorders stemming from early insults to the developing brain, resulting in alterations in muscle tone. While spasticity and dystonia are common motor disorders in CP, non-neural factors such as changes in muscle architecture contribute to muscle stiffness. Muscle stiffness in CP involves changes in muscle morphology and structure. Current treatments, such as botulinum toxin, have limitations, leading to exploration of alternative techniques like cryoneurolysis, hyaluronidase, and extracorporeal shockwave therapy. This brief review advocates for a comprehensive approach that considers both muscular and neurologic components of hypertonia, emphasizing the need for further research on cellular-level changes contributing to muscle stiffness. IMPACT: This review highlights the gap in current literature regarding the complex interplay between neural and non-neural factors in muscle stiffness and hypertonia in children with cerebral palsy (CP). While spasticity and dystonia are well studied, the review emphasizes the need for interventions addressing muscle morphology and extracellular matrix stiffness. It introduces emerging therapies like cryoneurolysis, hyaluronidase, and extracorporeal shockwave therapy, calling for more research on their long-term efficacy and safety.
... Cryoneurolysis is a form of thermal neurolysis in which a cryoprobe cooled from −20°C to −100°C (−88°C with nitrous oxide as a coolant) is used to freeze peripheral sensory nerves at or near the source of pain. 169,170 The mechanism of action is to locally freeze the nerve, which results in Wallerian degeneration of the axon and myelin distal to the injury, but preservation of the nerve sheath. Over time, the nerve regenerates at 1-2 mm per day along the intact nerve sheath to its target innervation. ...
... Over time, the nerve regenerates at 1-2 mm per day along the intact nerve sheath to its target innervation. 169 Another form of thermal denervation is radiofrequency ablation (RFA). 174,175 In contrast to cryoneurolysis, cooled RFA delivers radiofrequency energy to degrade nerve structures through ionic heating at a high thermal temperature of 60°C to disrupt or destroy neurons. ...
Osteoarthritis (OA) is a prevalent condition that affects nearly 528 million people worldwide, including 23% of the global population aged ⩾40, and is characterized by progressive damage to articular cartilage, which often leads to substantial pain, stiffness, and reduced mobility for affected patients. Pain related to OA is a barrier to maintaining physical activity and a leading cause of disability, accounting for 2.4% of all years lived with disability globally, reducing the ability to work in 66% of US patients with OA and increasing absenteeism in 21% of US patients with OA. The joint most commonly involved in OA is the knee, which is affected in about 60%–85% of all OA cases. The aging population and longer life expectancy, coupled with earlier and younger diagnoses, translate into a growing cohort of symptomatic patients in need of alternatives to surgery. Despite the large number of patients with knee OA (OAK) worldwide, the high degree of variability in patient presentation can lead to challenges in diagnosis and treatment. Multiple society guidelines recommend therapies for OAK, but departures from guidelines by healthcare professionals in clinical settings reflect a discordance between evidence-based treatment algorithms and routine clinical practice. Furthermore, disease-modifying pharmacotherapies are limited, and treatment for OAK often focuses solely on symptom relief, rather than underlying causes. In this narrative review, we summarize the patient journey, analyze current disease burden and nonsurgical therapy recommendations for OAK, and highlight emerging and promising therapies—such as cryoneurolysis, long-acting corticosteroids, and gene therapies—for this debilitating condition.
... Finally, pulsed radiofrequency stimulation (PRF) has been applied in the strategy of pain treatment, including neuralgia, where an electrical field and heat bursts to the targeted nerves are delivered through the needle tip of a catheter [91], but the technique is only described in a limited number of cases suffering from pain after ulnar nerve entrapment [92]. "Cryoneurolysis" may be a further option to treat localized peripheral pain, for example, related to a nerve branch, in patients after surgery for ulnar nerve entrapment [93]. Spinal cord stimulation (SCS) is one of the neuromodulators that is used to treat neuropathic pain [94,95], which is also an option to treat refractory pain, in combination with all the other techniques, in ulnar nerve entrapment. ...
Peripheral nerves consist of delicate structures, including a rich microvascular system, that protect and nourish axons and associated Schwann cells. Nerves are sensitive to internal and external trauma, such as compression and stretching. Ulnar nerve entrapment, the second most prevalent nerve entrapment disorder after carpal tunnel syndrome, appears frequently at the elbow. Although often idiopathic, known risk factors, including obesity, smoking, diabetes, and vibration exposure, occur. It exists in all adult ages (mean age 40–50 years), but seldom affects individuals in their adolescence or younger. The patient population is heterogeneous with great co-morbidity, including other nerve entrapment disorders. Typical early symptoms are paresthesia and numbness in the ulnar fingers, followed by decreased sensory function and muscle weakness. Pre- and postoperative neuropathic pain is relatively common, independent of other symptom severity, with a risk for serious consequences. A multimodal treatment strategy is necessary. Mild to moderate symptoms are usually treated conservatively, while surgery is an option when conservative treatment fails or in severe cases. The decision to perform surgery might be difficult, and the outcome is unpredictable with the risk of complications. There is no consensus on the choice of surgical method, but simple decompression is relatively effective with a lower complication rate than transposition.
... The rapidly generated ice ball causes axonotmesis. 9 The epineurium and perineum are preserved and serve as a tunnel for the treated axon's regeneration. 10,11 Recent case studies have shown that the reduction in spasticity and improvement in range of motion (ROM) can endure beyond the nerve's regeneration, for months to years. ...
Introduction: Spasticity of the knee extensors is a common presentation among patients with multiple sclerosis. The resulting stiff leg gait can result in increased risk of falls, heightened energy expenditure during gait, lowered gait speed, and compensatory gait mechanisms that increase wear on the hips. Cryoneurolysis is a novel percutaneous, minimally invasive treatment for focal spasticity. Methods: A single patient with multiple sclerosis was treated with cryoneurolysis of the femoral nerve branch to rectus femoris. The patient was followed for 15 months. Spasticity severity, gait speed, and patient reported outcomes were collected at each follow-up. Results: Spasticity severity as per the Modified Ashworth Scale was reduced at 1 month, with change persisting up to 15 months post-procedure. Range of motion as per the Modified Tardieu Scale showed gradual improvement over the 15-month period. Gait speed increased after the procedure from 21.15 seconds to 12.49 seconds for the 10 m walk test 1 month post-procedure, then slowed to baseline after 15 months. The patient's confidence in their gait improved and their independence was maintained throughout the follow-up period. Because of the regression in the 10 m walk test, the patient elected to have the procedure repeated after 15 months. Immediately after the procedure, the 10 m test time improved to 16.20 seconds.
... The target temperature for cryoneurolysis is below − 20 °C but above − 100 °C inducing axonotmesis, where Wallerian degeneration occurs with associated predictable regeneration. This causes Schwann cell disruption and axonal degeneration at the site of treatment, impacting the distal nerve conduction and disrupting pain signaling distal to the intervention [23]. Current models implement nitrous oxide or carbon dioxide as the boiling point of either gas (nitrous oxide: − 88 °C; carbon dioxide: − 79 °C) cannot be exceeded and thereby evades any possibility of damage to bystander connective tissue structures such as blood vessels, bone, and other nerve extracellular matrix and scaffold structures (endoneurium, perineurium, and epineurium are preserved), allowing ultimate Wallerian regeneration and repair of the freeze injury site.Cryoneurolysis techniques do not attain more dangerous temperatures, such as − 140 °C and colder which induce third and fourth degree nerve injury through neurotmesis with partial axonal fragmentation and loss of endoneurium and perineurium structures (irreversible injury). ...
Purpose of Review
Knee osteoarthritis is a debilitating chronic disease affecting nearly half of the world’s population at some point in their lives. Treatment of pain and loss of function associated with this disease has been limited. In this review, we seek to explore how neural interventions with ultrasound guidance may be an emerging option for non-pharmacologic pain relief in patients with knee osteoarthritis.
Recent Findings
Cryoneurolysis techniques have been demonstrated to provide pain relief out to 150 days post-treatment in knee osteoarthritis in select individuals. There have also been studies of cryoneurolysis pre-operatively to total knee replacement providing reduced pain, reduced opioid use post-operatively, and shorter hospital length of stay. Cooled radiofrequency ablation (CRFA) has been demonstrated to significantly reduce pain, improve functionality, and reduce pharmacologic needs in knee osteoarthritis out to 2 years. Both interventions appear to have increased accuracy with ultrasound, and CRFA appears to be associated with improved patient outcomes.
Summary
The research demonstrates the efficacy of both cryoneurolysis and cooled radiofrequency ablation in the treatment of knee osteoarthritis. Ultrasound guidance in neurolysis provides an additional tool with real-time, high-accuracy nerve localization. These therapies should be considered for certain patients to assist in pain management in the non-operative and post-operative phase of knee osteoarthritis management. Further research is needed to further define the long-term effects and the long-term utility of the techniques in knee pain.
... On the other hand, the use of cryoneurolysis, an opioid-sparing therapy in which cryoprobes freeze peripheral nerves, is becoming increasingly popular [55]. Cryoneurolysis causes nerves to undergo Wallerian degeneration, allowing relief from pain for up to 90 days as nerves regenerate [56,57]. The device for the procedure utilizes liquid nitrous oxide being converted to a gas, generating a temperature of −125°C [58]. ...
Careful perioperative pain management is crucial for good patient outcomes after surgery, as poorly controlled pain interferes with the ability of patients to recover to normal baseline function and increases postoperative morbidity and mortality. Although opioids have been the mainstay for treating postoperative pain, there has been a shift in favor of a multimodal analgesic approach, including regional anesthesia, as a way to circumvent opioid-related adverse events (e.g. nausea and vomiting, respiratory depression, sedation). In this chapter, we present an update on several recently developed regional anesthetic techniques, local anesthetic medications, as well as nerve block adjuncts with the potential to improve pain management in the perioperative setting. With more future studies, these novel methods may be incorporated into postsurgical recovery protocols and provide the opportunity to improve patient outcomes.
