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Cryoneurolysis, also referred to as cryoanalgesia, is a medical procedure that temporarily blocks nerve conduction along peripheral nerve pathways. The procedure, which inserts a small probe to freeze the target nerve, can facilitate complete regeneration of the structure and function of the affected nerve. Cryoneurolysis has been used to treat a variety of painful conditions.


Medical uses

A similar procedure that uses
radiofrequency Radio frequency (RF) is the oscillation rate of an alternating electric current or voltage or of a magnetic, electric or electromagnetic field or mechanical system in the frequency range from around to around . This is roughly between the upper ...
energy for
back pain Back pain is pain felt in the back. It may be classified as neck pain (cervical), middle back pain (thoracic), lower back pain (lumbar) or coccydynia (tailbone or sacral pain) based on the segment affected. The lumbar area is the most common ...
appears to have short-term benefit, but it is unclear if it has a long-term effect.


Mechanisms of action


Nerve anatomy

Each nerve is composed of a bundle of
axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...
s. Each axon is surrounded by the
endoneurium The endoneurium (also called endoneurial channel, endoneurial sheath, endoneurial tube, or Henle's sheath) is a layer of delicate connective tissue around the myelin sheath of each myelinated nerve fiber in the peripheral nervous system. Its com ...
connective tissue layer. These axons are bundled into fascicles surrounded by the
perineurium The perineurium is a protective sheath that surrounds a nerve fascicle. This bundles together axons targeting the same anatomical location. The perineurium is composed from fibroblasts. In the peripheral nervous system, the myelin sheath of each ...
connective tissue layer. Multiple fascicles are then surrounded by the epineurium, which is the outermost connective tissue layer of the nerve. The axons of myelinated nerves have a
myelin Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be ...
sheath made up of
Schwann cells Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory en ...
that coat the axon.


Nerve injury classification

Classification of nerve damage was well-defined by Sir Herbert Seddon and Sunderland in a system that remains in use. The adjacent table details the forms (
neurapraxia Neurapraxia is a disorder of the peripheral nervous system in which there is a temporary loss of motor and sensory function due to blockage of nerve conduction, usually lasting an average of six to eight weeks before full recovery. Neurapraxia is ...
, axonotmesis and
neurotmesis Neurotmesis (in Greek tmesis signifies "to cut") is part of Seddon's classification scheme used to classify nerve damage. It is the most serious nerve injury in the scheme. In this type of injury, both the nerve and the nerve sheath are disrupted. ...
) and degrees of nerve injury that occur as a result of exposure to various temperatures. Cryoneurolysis treatments that use
nitrous oxide Nitrous oxide (dinitrogen oxide or dinitrogen monoxide), commonly known as laughing gas, nitrous, or nos, is a chemical compound, an oxide of nitrogen with the formula . At room temperature, it is a colourless non-flammable gas, and has ...
(boiling point of −88.5 °C) as the coolant fall in the range of an axonotmesis injury, or 2nd degree injury, according to the Sunderland classification system. Treatments of the nerve in this temperature range are reversible. Nerves treated in this temperature range experience a disruption of the
axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...
, with Wallerian degeneration occurring distal to the site of injury. The axon and
myelin sheath Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be l ...
are affected, but all of the connective tissues (
endoneurium The endoneurium (also called endoneurial channel, endoneurial sheath, endoneurial tube, or Henle's sheath) is a layer of delicate connective tissue around the myelin sheath of each myelinated nerve fiber in the peripheral nervous system. Its com ...
,
perineurium The perineurium is a protective sheath that surrounds a nerve fascicle. This bundles together axons targeting the same anatomical location. The perineurium is composed from fibroblasts. In the peripheral nervous system, the myelin sheath of each ...
, and epineurium) remain intact. Following Wallerian degeneration, the axon regenerates along the original nerve path at a rate of approximately 1–2 mm per day. Cryoneurolysis differs from cryoablation in that cryoablation treatments utilize liquid nitrogen (boiling point of −195.8 °C) as the coolant, and therefore, fall into the range of a
neurotmesis Neurotmesis (in Greek tmesis signifies "to cut") is part of Seddon's classification scheme used to classify nerve damage. It is the most serious nerve injury in the scheme. In this type of injury, both the nerve and the nerve sheath are disrupted. ...
injury, or 3rd degree injury according to the Sunderland classification. Treatments of the nerve in this temperature range are irreversible. Nerves treated in this temperature range experience a disruption of both the axon and the endoneurium connective tissue layer.


History

The use of cold for pain relief and as an anti-inflammatory has been known since the time of
Hippocrates Hippocrates of Kos (; grc-gre, Ἱπποκράτης ὁ Κῷος, Hippokrátēs ho Kôios; ), also known as Hippocrates II, was a Greek physician of the classical period who is considered one of the most outstanding figures in the history o ...
(460-377 B.C). Since then there have been numerous accounts of ice used for pain relief including from the Ancient Egyptians and Avicenna of Persia (A.D.982–1070). In 1812 Napoleon's Surgeon General noted that half-frozen soldiers from the Moscow battle were able to tolerate amputations with reduced pain and in 1851, ice and salt mixtures were promoted by Arnott for the treatment of nerve pain. Campbell White, in 1899, was the first to use refrigerants medically, and Allington, in 1950, was the first to use liquid nitrogen for medical treatments. In 1961, Cooper et al. created an early cryoprobe that reached −190 °C using liquid nitrogen. Shortly thereafter, in 1967, an ophthalmic surgeon named Amoils used carbon dioxide and nitrous oxide to create a cryoprobe that reached −70 °C.


Devices


Cryoprobe

Cryoneurolysis is performed with a cryoprobe, which is composed of a hollow cannula that contains a smaller inner lumen. The pressurized coolant (nitrous oxide, carbon dioxide or liquid nitrogen) travels down the lumen and expands at the end of the lumen into the tip of the hollow cannula. No coolant exits the cryoprobe. The expansion of the pressurized liquid causes the surrounding area to cool (known as the Joule-Thomson effect) and the phase change of the liquid to gas also causes the surrounding area to cool. This causes a visible iceball to form and the tissue surrounding the end of the cryoprobe to freeze. The gas form of the coolant then travels up the length of the cryoprobe and is safely expelled. The tissue surrounding the end of the cryoprobe can reach as low as −88.5 °C with nitrous oxide as the coolant, and as low as −195.8 °C with liquid nitrogen. Temperatures below −100 °C are damaging to nerves. CRYO-S PAINLESS Cryoanalgesia device is the next generation of apparatus used by many experts in the field since 1992. The working medium for CRYO-S PAINLESS is carbon dioxide: (−78 °C) or nitrous oxide: (−89 °C), very efficient and easy to use gases.CRYO-S PAINLESS is controlled by a microprocessor and all the parameters are displayed and monitored on a LCD screen. Mode selection probe, cleaning and freezing can be performed automatically using footswitch or touch screen which allows to keep the site of a procedure under sterile conditions. Electronic communication (chip system) between the connected probe and device allows recognition of optimal operating parameters and auto-configures to cryoprobe characteristics. Pressure and gas flow are set automatically, any manual adjustment is not necessary. Cryoprobe temperature, cylinder pressure, gas flow inside of cryoprobe and procedure time are displayed during freezing. Built-in voice communication Built-in neurostimulation (sensory, motor).


Other Devices

The Endocare PerCryo Percutaneous Cryoablation device utilizes argon as a coolant and can be used with 4 different single cryoprobe configurations with a diameter of either 1.7 mm (~16 gauge) or 2.4 mm (~13 gauge) in diameter . The Myoscience Iovera° is a handheld device that uses nitrous oxide as a coolant and can be used with a three-probe configuration with a probe diameter of 0.4 mm (~27 gauge).


References

{{Reflist Neurology procedures Cryobiology