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Cryoneurolysis for Pain Management: Advantages, Indications & Future Directions
Olivia Reid • Updated Jul 31, 2024 • 148 hits
Cryoneurolysis is a medical procedure that uses extreme cold to temporarily disable nerves, thereby reducing pain without causing permanent nerve damage. Unlike traditional radiofrequency ablation (RF), cryoneurolysis offers the advantage of preserving nerve structures and promoting regeneration, making it a more nerve-friendly approach. Interventional radiologist Dr. Alexa Levey underscores the importance of proper patient selection and transparent communication to optimize outcomes, as well as looks forward to the broader adoption and ongoing research to solidify cryoneurolysis as a mainstream treatment.
This article features excerpts from the BackTable MSK Podcast. We’ve provided the highlight reel in this article, and you can listen to the full podcast below.
The BackTable MSK Brief
•Cryoneurolysis causes temporary nerve injuries, in which the nerve layers are preserved and can and regenerate, unlike radiofrequency ablation, which causes permanent nerve damage.
•Cryoablation allows for real-time monitoring of ice formation, providing precision and reducing the risk of collateral tissue damage.
•Identifying the most appropriate cryoneurolysis technique is an individualized approach that involves reviewing the patient's clinical history and imaging, as well as identifying the specific type and source of pain.
•In order to increase the more widespread adoption of cryoneurolysis, there is a need for comprehensive coding and research through collaborative efforts among medical professionals.
Table of Contents
(1) Cryoneurolysis vs Radiofrequency Ablation in Pain Management
(2) Cryoneurolysis Patient Selection
(3) Future Directions for Cryoneurolysis
Cryoneurolysis vs Radiofrequency Ablation in Pain Management
Cryoneurolysis offers several advantages over traditional radiofrequency ablation (RF) in pain management, particularly in its ability to cause reversible nerve injuries while preserving the integrity of nerve structures. Unlike RF, which often results in permanent nerve damage (Sunderland 3 or 4 injuries), cryoneurolysis induces a Sunderland type 2 injury, damaging the axon but leaving the nerve's protective layers intact. This feature is particularly beneficial for treating conditions where nerve regeneration is desired, such as in phantom limb pain or complex regional pain syndrome.
Cryoablation allows clinicians to visually monitor ice formation, enhancing precision and minimizing damage to surrounding tissues—a significant advantage over RF, which lacks this visibility and can lead to unpredictable tissue damage. Additionally, cryoablation's gentler impact on adjacent structures makes it a safer option for delicate areas, such as the neck, where important anatomical structures are present. The technique's adaptability for various nerve targets (e.g. stellate ganglions, lumbar sympathetics, and pudendal nerves) underscores its versatility and efficacy in diverse clinical scenarios.
[Dr. Jacob Fleming]
You also mentioned the difference between cryoneurolysis and cryotumor ablation. That is a really great point. I don't want to digress too much into that, but it brought up something that I want to talk about, I think is very important when talking about pain therapies in general. The workhorse of pain ablations has been radiofrequency for decades. You talk to most pain people, they probably haven't used much cryo at all, whereas medial branch rhizotomies, SI rhizotomies, whatever you want to do, it's all pretty much RF-based. As we begin to talk specifically about cryoneurolysis, what are the advantages over RF? Just in general of cryoneurolysis, when and why?
[Dr. Alexa Levey]
Actually I can talk to this because I got a lot of questions about that from the JVIR editor, because they said, "Oh, you can do cryoneurolysis or RF for stellates," and I'm like, "What is RF? The thing that I wrote?" I wrote a book chapter when I was in residency with Darren Kies and Mitchell Ermentrout for treatment of HCCs. I actually wrote about RF and cryo and microwave and why you'd use one, and irreversible electroporation and when you use one versus the other. That was about the extent of my experience with RF because people just are not trained to use it anymore unless you're doing basivertebral nerve ablation, unless you're doing median nerve ablation, like you had mentioned, or you're doing osteocool type ablation in bones. People are not using it anymore.
When we're talking about RF versus cryo and one-on-one, what are the advantages that people say? RF is a lot faster. Okay, great. I will argue that you can do cryoneurolysis, which again, cryoneurolysis, what you're trying to do is cause a Sunderland type 2 nerve injury, which is an injury that basically damages the axon, but leaves all the layers of the nerves intact. By the way, you can't get anything higher than that with cryo because no probes go colder than -100, so very possible. Versus with RFA, you always get a Sunderland 3 or 4, you are destroying the nerve. Because you don't need to spend that long freezing, you can do eight minutes, you can do 10 minutes. It's not going to be an entire 36-minute freeze-thaw cycle, for example. It will be longer, but not as long.
You can see the ice, you can see where it's forming. Remember, ice means zero degrees. Ice does not mean -22, which is actually 22 to 23, which is actually cell death. It just means zero. You can actually see when it's getting close to structures, it may cause inflammation, but won't cause damage. You can't see that with RF whatsoever. It's less predictable.
RF does cause adjacent tissue char when we're doing things in the neck with stellate ganglion. There's the esophagus and the inferior thyroidal artery and the vertebral artery. Again, you have some heat sink and you have the recurrent laryngeal nerve and you have the thyroid and you have the lung right there. It would probably be nice to have something that's a little gentler in the surrounding soft tissue, something that you could see when you're actively freezing. It's a little more predictable.
Something else too, again, talking about the Sunderland injuries, when you're bleeding a tumor or you're ablating a median nerve, those don't carry any motor fibers or anything. You're not really worried about that. Versus with cryo, you're causing a nerve injury, but you allow those to regenerate. Do you really want to do radiofrequency ablation of your splanchnic nerves and destroy them? They're bilateral. Just as God gave you two kidneys, they're probably important and you probably don't want to destroy them. Not saying you can't, but that's the thought process is that you are inducing a nerve injury versus permanent nerve damage, which permanent nerve damage, fine in some settings, not fine in other settings. You're able to see what you're doing versus you can't see what you're doing. It's more general around the surrounding soft tissues. Those are the reasons why I think there's been a lot more of a push for cryo.
[Dr. Jacob Fleming]
Got you. Tell us a little bit about the specific nerve targets you're using it for. Of course, you're doing a lot of work with stellates. What are some of the other ganglia or nerves that you're targeting?
[Dr. Alexa Levey]
If you ever told me I'd be a person becoming what somebody would call an expert in stellates, I would say, “no,” but I do a lot with stellates. I think it all depends on what you're doing, again, talking about nerve targeting, any nerve, honestly. I've done it for phantom limb. I actually published a case report of doing a posterior tibial nerve block and cryo ablation for phantom toe pain after traumatic amputation from atheroembolism. That's something you can do. I've done it for complex regional pain syndrome. I've done stellates for those as well as for VTAC, as well as for long COVID, which is a whole nother topic, as well as for pain control for pancoast tumors. I've done lumbar sympathetics for complex regional pain syndrome. I've done obturator and pudendal nerves, pudendal for pudendal neuralgia, obturator nerves and pudendal for tumoral encasement, superior hypogastric nerves. Those are actually only blocks, no cryos, it's too hard to work around. Those would actually be an ethanol. I've done femoral nerves. Actually, a lot of motor nerves I've done wherever there's tumoral encasement.
Pretty much any nerve you can think of, you can do a cryo of if you can get there safely. The only one I haven't tried yet is I've done a couple of trigeminal nerve blocks and I haven't tried sticking a cryoprobe in somebody's face.
[Dr. Jacob Fleming]
Got you. That's one where the RF technique has been described over the years.
[Dr. Alexa Levey]
Yes, pulsed RF.
[Dr. Jacob Fleming]
You're right. Cryo, potentially could be really great for that, especially, talking about, you mentioned the Sutherland 2 injury, and that it's allowing the nerve to go through that regenerative process. I don't know if this is totally just wrong to think about it this way, but I almost think about it as a neuromodulation sort of thing. We're not just carpet-bombing the crap out of it, but giving it time to reprogram.
[Dr. Alexa Levey]
Exactly. The way Prolovo describes it, and actually I can also back up too and say, obviously I've done celiac, splanchnic, adrenal ganglions, any regulatory center, I've pretty much cryo'd. It's 100% what you're doing, you're basically rebooting the nerve. You're saying, "You are overactive, you are overstimulated. Let me make it so nothing gets transmitted down to you for a while so you can regroup and get your stuff together. You're okay, you're fine, stop sending signals."
[Dr. Jacob Fleming]
Just a digression, is there anything more radiology than saying, "Hey, unplug it and plug it back in again"?
[Dr. Alexa Levey]
No.
[Dr. Jacob Fleming]
IT, radiology, that's our life and training. Hey, it works.
[Dr. Alexa Levey]
On and off. No it totally does. It's great. When it works, it works super well, which is really cool. I really enjoyed it and started getting, I guess, a little creative with it.
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Cryoneurolysis Patient Selection
Interventional radiologists are uniquely positioned to advance pain management therapies through innovative approaches like cryoablation. Dr. Levey highlights the importance of thorough patient evaluations and transparent discussions about expected outcomes and risks.
Effective patient selection involves detailed clinical assessments and imaging reviews to identify suitable candidates. Dr. Levey emphasizes the necessity of performing diagnostic nerve blocks before proceeding to cryoablation to ensure efficacy and patient satisfaction. Maintaining clear communication and setting realistic expectations is crucial for successful pain management, especially in complex cases involving chronic pain or cancer-related discomfort.
[Dr. Jacob Fleming]
I do want to talk about specifics in terms of, how do you talk to patients about this? Obviously, you just listed off a myriad of different topics or different targets, so many different things, but talk to us a little, in general, about the process of patient selection, how you generally plan your procedures and the discussion in clinic with the patient: what can be expected, talking about risks, and that sort of thing.
[Dr. Alexa Levey]
Sure. That's all these super important topics. Number one, everybody's a candidate. There's always something you could potentially do for someone, and if I can't do it, I know who can. I still have connections with other anesthesiologists, PMNR colleagues, neurology, where I can send the patient somewhere else if there's something that I can't do. Becoming a person who is known for doing pain, if you don't do it all, then you need to know people who can and you need to be able to get them in and be able to network them out because that is your patient. That is the most important thing. You take care of that patient like your mother or your brother, somebody you actually like in your family and treat them like family because there is nothing worse than to be in pain and there's nothing a patient wants more than to be heard and to be understood. Hearing them out and evaluating. There's nothing more than a doctor who wants to. Your patient's in pain and they're terrible, they can't manage it? Let me help you. I will talk to them. If they need something else, I'll discuss it with you and I will get them referred out so they can get their problem fixed. That is the best thing you can do and say to refer and to build your practice. That's the first thing.
My phone is always on for my referrers. All my patients have my email address. I am constantly checking it. If I had a second phone, my patients would have my phone. Being accessible is super important. When I'm evaluating a patient for pain, imagine, is it chronic or is it cancer related? Let's talk about cancer related. I had one that got referred to me over the weekend that I looked at today, a patient who has metastatic cancer of an unknown primary and just has this diffuse nonspecific abdominal pain. Normally what you want to do is read the patient's history, find out if it's acute, if it's chronic, if they have cancer. You want to look at some type of cross-sectional imaging and you want to see first, is there anything on that imaging that looks like it could cause the pain described in the note, some kind of general pain in one area or not? Is there a mass encasing the femoral nerve that's causing pain to shoot down their leg? Do they have a cervical cancer that's invading their obturator or pudendal nerves, something that you could target? Is there something that is in the splanchnic bed that is causing pain, or is there nothing and maybe you just try a splanchnic block to get something general? Look at the notes, number one. Look at cross-sectional imaging, number two, to try to determine some potential targets.
For this particular patient, generalized abdominal pain, it was the most unimpressive CT I've ever seen, retroperitoneal adenopathy, and just diffuse abdominal pain, which she was describing. I looked up a little higher and I realized just inferior to the right where the celiac plexus is coming off at the celiac axis retrocrural is this massive node. Then, I look a little more cranial and there's a lot of dirt in the fat, and I'm like, "Gosh, this node is invading the splanchnic plexus and it's probably contributing to her abdominal pain." What if I planned after I talked to her to treat the splanchnic plexus and then try to treat that little node and cause some regression back from the diaphragm and from the crura and see if that helps a little bit? That's a thought process of things I go through.
Next most importantly, go see the patient, go see the patient yourself. I had people ask me, "This patient has 8 out of 10 pain here. What would you do?" I said, "Where? Can they point to it with one finger? Is it sharp? Is it stabbing? Is it burning? Does it radiate? Does anything make it better? Does anything make it worse? How does it feel when they take pain meds? Does it regress at all? Is there anything that exacerbates it?" You really have to get incredibly granular with pain patients because what you'll find is often you will help pretty much every single patient but not to the degree that they would normally think about it, if that makes sense. You can make a change and impact everybody's pain, who you treat, but it will be in one certain sector of what they categorize as their pain. They'll get less crampy. They'll be able to eat more. They'll still get a crescendo of their pain, but it will be to a five or six versus a 9 out of 10, and it will go away faster. The more granular you can be with your patient interview, the better you will be at helping your patients succeed in getting their pain under control and realize that they are making progress.
That also being said, the first thing I say to patients when I see them, and it's the hardest thing to say to somebody is, "I'm sorry, but there's no way I'm going to be able to make your pain zero. That's not possible. If anybody tells you that, they're lying to you. That's a hard truth to accept that you're always going to have some level of pain, but I am here to help you manage it. I am here to help you get through it. I am here to hopefully reduce it by 50%, if not more. I am here to hopefully get you on a lower dose of opioids so that you can be more active in your life, you can get out, you can drive, you're not sleeping all day, you don't feel constipated, and you don't feel nauseous. If that doesn't work, here's plan B." I think having a very honest and real conversation with the patient is the most important thing. There are no magic wands for pain. It is always going to be multimodal in management. A big part of what I do is therapy, 100%. I would say that my initial clinic visits are usually about 35 to 40 minutes and the follow-ups are much faster. That's actually for any patient I see. That's just the way I am. I like to describe things, everything, and be very thorough so that if anything comes up, they can feel free to ask me. My subsequent visits actually end up being a lot shorter.
With pain too, when you do that, you can actually help patients identify what kind of pain they're having, get those granular things, and then you have something to compare to. Then, you could show them their progress. I can say my complex regional pain syndrome patients I've treated, they actually continued to improve. I think that's just because of learning to accept that this is their new baseline and their new normal, not because I didn't do anything, I usually get them a decent amount of pain relief, but them willing to adapt, being able to do more physical therapy, and learning to do some cognitive restructuring about what their current life is. That's so important. That's how you maintain a practice. That's why I can say I love my pain patients. They're amazing. People are like, "Are you crazy? They're so hard." It's like, no, they just want to be heard. They need little goals, little things to say, "Look, this is what you said before. This is what's happening. That's good. Not to say that your current pain is not important, but look where we have made strides and made improvements."
Those are things I really focus on in the clinic visit. Of course, I talked about that in my physical exam, asking about history, blood thinners, typical procedural things, chronic health issues, and then I plan for a procedure if I have something to target. Usually I have multiple steps after that.
General risk with cryo, gosh, it depends. Is it going to be close to the skin and they can get frostbite? Depending on the pathophysiology of the disease, when I cryo a stellate ganglion for VTAC and for complex regional pain syndrome, they do great. Some get Horner's. When I do it for long COVID, a third of them get Horner's and they get a raging neuritis, which some describe as the worst pain in their life, which goes away after six weeks, very predictably. You have to talk to people about that and tell them how to manage it and guide them through it, have follow-up visits, tramadol for pain, lidoderm patches for the shooting neuritis, anti-inflammatories, bedroll dose pack. You have to be able to handle all those things.
Also, it brings up another really big important point. You should almost, I say almost never because there are situations I do, go straight to cryo. You do a block first. You need to make sure people have success with the block so that they can want to have longer lasting relief and see that it's actually efficacious. Especially, I have people coming to me and asking me questions now about just doing cryo for long COVID. Don't do that. Not a good idea to go straight there. Because of the side effects of having the cryo in that particular pathophysiology, you're not going to have any more patients after your first one.
Future Directions for Cryoneurolysis
To make cryoneurolysis more widely adopted in pain management, there is a need for comprehensive research and development of standardized codes. Overcoming the barriers to conducting good research requires significant support from the interventional community and is crucial for mainstream acceptance and accessibility for patients. Retrospective studies can help build the necessary literature to promote cryoneurolysis.
There is also a growing interest in non-surgical approaches for treating desmoid tumors, using TK inhibitors, cryoablation, and embolization, which could eventually become part of standard care guidelines. More research and collaboration among colleagues are essential to integrate these innovative treatments into established protocols and improve patient outcomes.
[Dr. Jacob Fleming]
My next question that I had written here as I'm looking at them, wow, this is really pretty unhelpfully vague is just future applications of cryo. We've talked about current applications of cryo and it almost seems science fiction.
I'm going to narrow that a little bit and just say, what are you excited to see happen with cryoneurolysis in the next couple of years in terms of maybe things being more widely adopted or trying out new targets? What's on your mind that you're really wanting to get into next?
[Dr. Alexa Levey]
Honestly, it's going to be having it be more widely adopted. For that, we need those codes. We need full-fledged codes. For that, we need research. That's something I know that I am personally trying to work on. It's so hard. There are so many barriers to doing good research right now, and you need a lot of support in order to do it. That's really going to be the key to getting and pushing things forward and making them become more mainstream and more acceptable and then more accessible to patients. I think that starting off with anything you can do retrospectively to just show and start to beef up the literature is really going to help it take off. I think that there's a lot of research to be done.
Actually, what I'm excited about, it took me three years at UT to beat into the like, "Oh my gosh, why are you resecting desmoids? We should cryo these. We should do TK inhibitors. We can do embolizations." Finally, something that's on the forefront. An oncologist I work with came up with a protocol where you can discuss TK inhibitor, and then after TK inhibitor, do you consider cryo or do you consider embolization? There's this really cool desmoid tumor of the foot I saw. I was like, "Gosh." It was previously resected and irradiated. I'm like, "Oh, well, if I cryo that, I'm going to destroy all those tendons and everything else, but I can try embolization. I can do embolization with doxorubicin, which is local, and then we'll go to the lung." Those are really responsive to doxorubicin, something else cool you can do. All these things we can do and get into this world of, say, for example, I guess something would be cool, more so see it more of a standard of care treatment in some desmoids in certain desmoid tumor treatments. I think I would like to see that start to pop up in the NCCN guidelines, especially since resectioning locally recur a lot.
I think that that is some things that are on the forefront right now that we're going to start seeing more of cryo, the treatment of desmoid tumors, cryoneurolysis, I think becoming more of a standard of care with cancer patients, especially once we start coming up with more data. Celiac blocks are already something that are looked at there, so I'm very excited to see that. I think those are probably the main things, but I think really it's going to take a lot more research, a lot more talking, and a lot more acceptance from people. It's going to take our colleagues helping to push for it to help get it more mainstream.
[Dr. Jacob Fleming]
It's definitely a team effort. I think the more that we can get the knowledge out there about what's even possible, and I have learned so much just being able to talk to you tonight about what is possible using this. This is something that I'm really into. Talking to some of this stuff, even to some of my colleagues who are physicians, they're like, "What?" It's like science fiction. IR has been that way for a long time. Now, some of the things that we have pioneered that used to be unthinkable are now common, done every day, and to the point that other specialties steal it. That's a little joke.
[Dr. Alexa Levey]
Or, we teach them, which is our own problem too, which we shouldn't be.
[Dr. Jacob Fleming]
Exactly. That's just a little joke. We're all about collaboration, right? We're all about collaboration.
[Dr. Alexa Levey]
Yes, but I will say people used to drill holes in people's heads to relieve pressure. Then, intrathecal cocaine was a real thing. The good old days, but all these things came from somewhere and you have to try and you have to see what it works. I think once, especially if you show people that you're collaborative and stuff, they'll be willing to let you try and let you work with them. Then slowly, things start becoming more mainstream and more accepted. Then things start coming out. Really, I think it does take, as I keep hammering on that collaborative nature for all this stuff to get published and become what is the new standard of care. I think cryo is well on the way for that, for pain management, as well as for treatment of certain syndromes.
Podcast Contributors
Dr. Alexa Levey
Dr. Alexa Levey is an interventional radiologist, interventional pain proceduralist, and assistant clinical professor in Houston, Texas.
Dr. Jacob Fleming
Dr. Jacob Fleming is a diagnostic radiology resident and future MSK interventional radiologist in Dallas, Texas.
Cite This Podcast
BackTable, LLC (Producer). (2023, December 18). Ep. 37 – Cryoneurolysis Pearls & Pitfalls [Audio podcast]. Retrieved from https://www.backtable.com
Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.
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