Cryoanalgesia Treatment

History of CryoanalgesiaCold has been used to relieve pain since the days of Hippocrates in ancient Greece. Modern cold therapy, or cryoanalgesia, has been around since the 1950s and is a trusted technology for treating pain.

  • 400 BC

    400 BC

    Hippocrates uses cold to relieve swelling bleeding and pain.

  • 1050


    An Anglo-Saxon monk uses cold as a local anesthetic.

  • 1899


    campbell White is the first to employ refrigerants for medical use.

  • 1961


    Dr Irving S. Cooper develops device with hollow tube to deliver pressurized nitrogen and achieve -190°C at the tip.

  • 1967


    Setrag Zacarian introduces a hand-held self-pressurized cryogen spray device.

  • 1976


    Lloyd et al proposes that cryoanalgesia is superior to other methods of peripheral nerve destruction.

  • 2013


    The iovera° treatment system is launched. It delivers targeted cold to a peripheral nerve, immediately relieving pain.

Cryoanalgesia (also known as cryoneurolysis) is the destruction of the signal carrying parts of a nerve. It is a small subset of treatments under the broad umbrella of cryotherapy.

Until now, traditional cryotherapy treatments were invasive and used large complicated machines.

The iovera° system has revolutionized the delivery of cryoanalgesia.  With the iovera° system, healthcare providers are able to deliver precise, controlled doses of cold temperature only to the targeted nerve through a handheld device. This procedure is safe and does not damage or destroy the surrounding tissue.2

Cryoanalgesia with the iovera° system To understand how cryoanalgesia is achieved with the iovera° system, it is important to first understand the varying degrees of nerve injury and the temperatures at which they occur. Sunderland described and classified the basic types of nerve injuries to assist in the prognosis and treatment strategy for these injuries.3,4

Sunderland Nerve Injury Classification4-6


1st Degree +10oC to -20oC

Neuropraxia – interruption of conduction; Short recovery time

2nd Degree -20oC to -100oC

Axonotmesis – Loss of continuity of the axon; Wallerian degeneration; preservation of endo- peri- and epineurium

Non Reversible

3rd/4th Degree Colder than -140oC

Neurotmesis – Loss of continuity; some loss of continuity of epineurium and perineurium; endoneurium may or may not be disrupted (liquid nitrogen); Not possible with the iovera°

5th Degree

Transection (Severe Neurotmesis) – Gross loss of continuity; Not possible with the iovera°


Axonotmesis involves loss of the relative continuity of the axon and its covering of myelin but preserves the connective structure of the nerve (the endoneurium, epineurium and perineurium).

Other characteristics:

  • Wallerian degeneration occurs distal to the site of injury
  • When axonotmesis affects a sensory nerve, the sensory deficits occur distal to the site of lesion
  • Axonal regeneration occurs at a rate of 1 to 2 mm per day7, after which sensory signaling is restored
Nerve Anatomy


  1. Radnovich 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. Osteoarthritis Cartilage. 2017;25(8):1247-1256.
  2. Hsu M, Stevenson FF. Wallerian degeneration and recovery of motor nerves after multiple focused cold therapies. Muscle Nerve. 2015;51(2):268-275.
  3. Sunderland S. A classification of peripheral nerve injuries producing loss of function. Brain. 1951;74(4):491-516.
  4. Sunderland S. Nerves and Nerve Injuries. London, United Kingdom: Churchill Livingstone; 1968:180.
  5. Seddon HJ. Three types of nerve injury. Brain. 1943;66(4):237-288.
  6. Ilfeld BM, Preciado J, Trescot AM. Novel cryoneurolysis device for the treatment of sensory and motor peripheral nerves. Expert Rev Med Devices. 2016;13(8):713-725.
  7. Evans PJ. Cryoanalgesia: the application of low temperatures to nerves to produce anaesthesia or analgesia. Anaesthesia. 1981;36(11):1003-1013.

IndicationThe iovera° system is used to destroy tissue during surgical procedures by applying freezing cold. It can also be used to produce lesions in peripheral nervous tissue by the application of cold to the selected site for the blocking of pain. It is also indicated for the relief of pain and symptoms associated with osteoarthritis of the knee for up to 90 days. The iovera° system is not indicated for treatment of central nervous system tissue.

Important Safety Information

ContraindicationsThe iovera° system is contraindicated for use in patients with the following:

  • Cryoglobulinemia, paroxysmal cold hemoglobinuria, cold urticaria, Raynaud’s disease, and open and/or infected wounds at or near the treatment site

Potential ComplicationsAs with any surgical treatment that uses needle-based therapy and local anesthesia, there is a potential for site-specific reactions, including, but not limited to:

  • Ecchymosis, edema, erythema, local pain and/or tenderness, and localized dysesthesia

Proper use of the device as described in the User Guide can help reduce or prevent the following complications:

  • At the treatment site(s): injury to the skin related to application of cold or heat, hyper- or hypopigmentation, and skin dimpling
  • Outside the treatment site(s): loss of motor function