What if knee pain could be treated by temporarily interrupting pain signals — without permanently destroying the nerve?
This is the concept behind cryoneurolysis, a technique that uses controlled low temperatures to target peripheral sensory nerves.
One of the best-known devices using this technology is iovera°.
In June 2026, Pacira BioSciences announced an agreement for Zimmer Biomet, one of the world’s leading companies in hip and knee arthroplasty, to acquire the iovera° business.
As an arthroplasty surgeon in Japan, I find this development particularly interesting.
I have been interested in peripheral nerve-targeted treatments for knee osteoarthritis (OA) for some time, because there remains an important treatment gap between conventional conservative care and joint replacement.
Cryoneurolysis may become one of the technologies capable of helping to fill that gap.
What You Will Learn in This Article
- What iovera° and cryoneurolysis are
- How cryoneurolysis temporarily interrupts pain signals
- Why Wallerian degeneration allows subsequent nerve regeneration
- Potential applications in knee osteoarthritis
- Potential applications before and after total knee arthroplasty (TKA)
- Why Zimmer Biomet’s move into cryoneurolysis is noteworthy
- Why this technology may be particularly relevant to the future of knee OA treatment
What Is iovera°?
iovera° is a medical device designed to perform cryoneurolysis.
The treatment targets peripheral sensory nerves involved in transmitting pain from the knee and applies controlled low temperatures through a specialized probe.
This temporarily interrupts nerve conduction and reduces the transmission of pain signals.
Conventional nonsurgical treatments for knee OA include:
- Analgesic medications
- Intra-articular injections
- Physical therapy and exercise
- Bracing
Cryoneurolysis takes a fundamentally different approach:
instead of treating the joint alone, it directly targets the peripheral nerves carrying the pain signal.
How Does Freezing a Nerve Reduce Pain?
Cryoneurolysis exposes a targeted peripheral nerve to controlled low temperatures, producing a temporary interruption of axonal conduction.
An important biological process involved is Wallerian degeneration.
When an axon is appropriately injured, the portion of the axon distal to the treatment site undergoes degeneration.
Importantly, with appropriately performed cryoneurolysis, the connective tissue framework surrounding the nerve can remain intact.
This preserved structure provides a pathway along which the axon can subsequently regenerate.
In other words, cryoneurolysis is not intended to permanently cut or destroy the nerve.
It is designed to produce a temporary interruption of nerve conduction, followed by gradual axonal regeneration and recovery of nerve function.
Reversibility Is One of the Most Interesting Features of Cryoneurolysis
Several technologies can target the sensory nerves responsible for knee pain, including radiofrequency ablation (RFA).
One reason I am particularly interested in cryoneurolysis is its concept of temporary nerve interruption followed by nerve regeneration.
Its effect is not intended to be permanent.
This may initially sound like a disadvantage, but in the treatment of a chronic condition such as knee OA, reversibility can also be an attractive characteristic.
Many patients with knee OA find themselves in an uncomfortable therapeutic gap:
“Conservative treatment is no longer controlling my pain, but I am not ready for knee replacement.”
This is precisely the clinical space in which peripheral nerve-targeted therapies deserve further investigation.
Cryotherapy Is Already Used Across Multiple Fields of Medicine
Using controlled low temperatures to modify biological tissue is not unique to orthopaedics.
Cryo-based technologies are already used across several areas of medicine.
In cardiology, cryoballoon ablation is an established technique for pulmonary vein isolation in patients with atrial fibrillation.
In otolaryngology, cryotherapy targeting the posterior nasal nerve has been developed for patients with chronic rhinitis.
In pain management and perioperative medicine, cryoneurolysis has also been investigated for applications including:
- Intercostal nerve treatment for pain associated with thoracic procedures
- Peripheral neuropathic pain
- Selected neuromas and other peripheral nerve pain conditions
These treatments are not equivalent: they target different tissues and have different therapeutic goals.
However, they demonstrate a broader principle:
controlled cold can be used as a therapeutic energy source to selectively modify tissue or nerve function.
Cryoneurolysis for knee pain represents another application of this broader cryotechnology platform.
What Does the Evidence Say About Knee Osteoarthritis?
Cryoneurolysis, including treatment with iovera°, has already been investigated in several clinical studies involving patients with knee osteoarthritis.
These include:
- Randomized controlled trials evaluating pain and function in knee OA
- Studies comparing cryoneurolysis with sham treatment
- Studies evaluating changes in pain, function and quality of life after treatment
Some studies have demonstrated meaningful improvements in pain and function.
However, results across the literature are not completely uniform.
At present, I believe the most appropriate interpretation is that cryoneurolysis is a promising treatment strategy, but important questions remain regarding patient selection, optimal nerve targets, procedural technique and duration of benefit.
Cryoneurolysis Is Also Being Studied Around Total Knee Arthroplasty
The potential role of cryoneurolysis is not limited to delaying or avoiding surgery.
It has also been investigated as part of perioperative pain management for total knee arthroplasty (TKA).
Clinical studies have examined preoperative cryoneurolysis of sensory nerves around the knee and its potential effects on:
- Postoperative pain
- Analgesic and opioid requirements
- Functional recovery after TKA
For an arthroplasty surgeon, this is an important point.
The future of knee replacement is not only about improving implants, robotics or surgical technique.
Improving the entire patient journey — including pain management before, during and after surgery — is equally important.
Zimmer Biomet’s Agreement to Acquire the iovera° Business
On June 30, 2026, Pacira BioSciences announced an agreement to divest its iovera° business to Zimmer Biomet.
Zimmer Biomet is one of the world’s major orthopaedic companies, with a particularly strong presence in hip and knee reconstruction.
From an arthroplasty perspective, the addition of a peripheral nerve-targeted pain technology to such a portfolio is noteworthy.
Knee OA treatment should not be viewed simply as:
“The joint hurts, therefore replace the joint.”
There is an entire continuum of care between the onset of symptomatic osteoarthritis and joint replacement — as well as an important period of pain management before and after surgery.
Where cryoneurolysis ultimately fits within this continuum remains to be determined.
But this is precisely why the technology is interesting.
iovera° and Cryoneurolysis in Japan
As of August 2026, iovera°-based cryoneurolysis is not a routinely available treatment for knee osteoarthritis in Japan in the way it is used in the United States.
Our center does not currently provide iovera° as part of routine insured clinical care.
Nevertheless, several characteristics of cryoneurolysis make it particularly interesting:
- It is a non-pharmacological approach to pain modulation
- It can target specific peripheral sensory nerves
- Axonal regeneration provides the biological basis for reversibility
- It may have a role in patients who are not yet ready for joint replacement
- It may also have applications in perioperative TKA pain management
For these reasons, I believe cryoneurolysis deserves serious attention as the treatment landscape for knee OA continues to evolve.
A Perspective from a Japanese Arthroplasty Surgeon
As an arthroplasty surgeon, my primary role is to provide high-quality joint replacement when it is truly needed.
But treating knee osteoarthritis should not begin and end with arthroplasty.
I have long been interested in peripheral nerve-targeted approaches to knee pain, particularly the possibility of treating pain pathways more selectively rather than simply escalating medication, injections and ultimately surgery.
This interest has also extended to medical device innovation. I am currently an inventor on a patent application related to a novel technology for peripheral nerve-targeted treatment of knee pain.
The technology under patent application is independent of iovera° and is mentioned here to disclose my ongoing research and development interest in this field.
Cryoneurolysis is especially compelling because it combines two concepts:
targeted interruption of pain transmission and subsequent biological nerve regeneration.
There are still many questions to answer.
Which nerves should we target? Which patients are most likely to benefit? Can targeting strategies become more anatomically precise? How should cryoneurolysis be integrated with conservative treatment and arthroplasty?
These are not reasons to dismiss the technology.
They are the reasons this field is worth exploring.
Zimmer Biomet’s agreement to acquire the iovera° business makes this an especially interesting moment for cryoneurolysis.
I will be closely following how this technology develops globally — and particularly how peripheral nerve-targeted treatment for knee OA may eventually evolve in Japan.
Conclusion
iovera° is a cryoneurolysis system designed to temporarily interrupt pain transmission through targeted peripheral nerves using controlled low temperatures.
Through Wallerian degeneration, nerve conduction can be interrupted while the preserved connective tissue framework allows subsequent axonal regeneration.
This combination of targeted pain modulation and biological reversibility makes cryoneurolysis an intriguing technology.
Clinical research has already explored its use in knee osteoarthritis and around total knee arthroplasty, although further evidence is needed to determine optimal patient selection and treatment strategies.
For patients with knee OA, the future may not simply be about choosing between conservative treatment and joint replacement.
There may be an important therapeutic space between them.
Cryoneurolysis may become part of that space.
References
- Radnovich R, et al. Cryoneurolysis to treat the pain and symptoms of knee osteoarthritis: a multicenter, randomized, double-blind, sham-controlled trial. Osteoarthritis Cartilage. 2017;25(8):1247-1256.
- Mihalko WM, et al. 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. J Arthroplasty. 2021.
- U.S. Food and Drug Administration. iovera° System. 510(k) K220656.
- Pacira BioSciences. Pacira BioSciences Announces Agreement to Divest its iovera° Business to Zimmer Biomet. June 30, 2026.
About Our Joint Replacement Center
At Kyoto Renaissance Hospital Joint Replacement Center, we specialize in the treatment of hip and knee disorders, including total hip and total knee arthroplasty.
This article was written by Takashi Fujii, MD, Director of the Joint Replacement Center at Kyoto Renaissance Hospital, Japan, and a board-certified orthopaedic surgeon specializing in hip and knee arthroplasty.
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