Cryoneurolysis, also referred to as cryoanalgesia, is a medical procedure that temporarily blocks

nerve conduction An action potential (also known as a nerve impulse or "spike" when in a neuron) is a series of quick changes in voltage across a cell membrane. An action potential occurs when the membrane potential of a specific cell rapidly rises and falls. T ...

along

peripheral nerve A nerve is an enclosed, cable-like bundle of nerve fibers (called axons). Nerves have historically been considered the basic units of the peripheral nervous system. A nerve provides a common pathway for the electrochemical nerve impulses called ...

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

Cryoneuralysis has been used to relieve pain after

thoracotomy A thoracotomy is a surgical procedure that involves cutting open the chest wall to gain access into the pleural cavity, It is mostly performed by specialist cardiothoracic surgeons, although emergency physicians or paramedics occasionally also ...

mastectomy Mastectomy is the medical term for the surgical removal of one or both breasts, partially or completely. A mastectomy is usually carried out to treat breast cancer. In some cases, women believed to be at high risk of breast cancer choose to have ...

, and knee or shoulder

arthroplasty Arthroplasty (literally " e-orming of joint") is an orthopedic surgical procedure where the articular surface of a musculoskeletal joint is replaced, remodeled, or realigned by osteotomy or some other procedure. It is an elective procedure that ...

. Combined with

ultrasound imaging Medical ultrasound includes diagnostic techniques (mainly imaging) using ultrasound, as well as therapeutic applications of ultrasound. In diagnosis, it is used to create an image of internal body structures such as tendons, muscles, join ...

, the procedure can be administered using a hand-held device in an office, and appears to provide an expedient, safe, and nonpharmacological option for treating various chronic pain conditions.

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 American and British English spelling differences#-re, -er, spelling differences) is a long, slender cellular extensions, projection of a nerve cell, or neuron, ...

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 comp ...

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 The epineurium is the outermost layer of dense irregular connective tissue surrounding a peripheral nerve. It usually surrounds multiple nerve fascicles as well as blood vessels which supply the nerve. Smaller branches of these blood vessels penet ...

, which is the outermost connective tissue layer of the nerve. The axons of myelinated nerves have a

myelin Myelin Sheath ( ) is a lipid-rich material that in most vertebrates surrounds the axons of neurons to insulate them and increase the rate at which electrical impulses (called action potentials) pass along the axon. The myelinated axon can be lik ...

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 glial cell, satellite ...

that coat the axon.

Classification and mechanism

Nerve injury classification table of temperatures required for injury

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 Axonotmesis is an injury to the peripheral nerve of one of the extremities of the body. The axons and their myelin sheath are damaged in this kind of injury, but the endoneurium, perineurium and epineurium remain intact. Motor and sensory function ...

and neurotmesis) and degrees of nerve injury that occur as a result of exposure to various temperatures, with the intent to interrupt nerve traffic and relieve pain. Cryoneurolysis treatments that use

nitrous oxide Nitrous oxide (dinitrogen oxide or dinitrogen monoxide), commonly known as laughing gas, nitrous, or factitious air, among others, is a chemical compound, an Nitrogen oxide, oxide of nitrogen with the Chemical formula, formula . At room te ...

(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, usually within a few months. Nerves treated in this temperature range experience a disruption of the

, with

Wallerian degeneration Wallerian degeneration is an active process of degeneration that results when a nerve fiber is cut or crushed and the part of the axon distal to the injury (which in most cases is farther from the neuron's cell body) degenerates. A related process ...

occurring distal to the site of injury. The axon and

myelin sheath Myelin Sheath ( ) is a lipid-rich material that in most vertebrates surrounds the axons of neurons to insulate them and increase the rate at which electrical impulses (called action potentials) pass along the axon. The myelinated axon can be lik ...

are affected, but all of the connective tissues (

, and

) 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 Cryoablation is a process that uses extreme cold to destroy tissue. Cryoablation is performed using hollow needles (cryoprobes) through which cooled, thermally conductive fluids are circulated. Cryoprobes are positioned adjacent to the target in ...

in that cryoablation treatments use

liquid nitrogen Liquid nitrogen (LN2) is nitrogen in a liquid state at cryogenics, low temperature. Liquid nitrogen has a boiling point of about . It is produced industrially by fractional distillation of liquid air. It is a colorless, mobile liquid whose vis ...

(boiling point of −195.8 °C) as the coolant, and therefore, fall into the range of a neurotmesis 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. The efficacy of cryoneuralysis procedures for pain relief depend on the proximity of the probe to the targeted nerve, surface area of tissue covered by the probe, the rate and duration of cold treatment, and the temperature applied.

History

The use of cold for pain relief and as an anti-inflammatory has been known since the time of

Hippocrates Hippocrates of Kos (; ; ), also known as Hippocrates II, was a Greek physician and philosopher of the Classical Greece, classical period who is considered one of the most outstanding figures in the history of medicine. He is traditionally referr ...

(460–377 BC). Since then there have been numerous accounts of ice used for pain relief including from the Ancient Egyptians and Avicenna of Persia (982–1070 AD). 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 Cryosurgery (with ''cryo'' from the Ancient Greek ) is the use of extreme cold in surgery to destroy abnormal or diseased tissue; thus, it is the surgical application of cryoablation. Cryosurgery has been historically used to treat a number of ...

, 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 In thermodynamics, the Joule–Thomson effect (also known as the Joule–Kelvin effect or Kelvin–Joule effect) describes the temperature change of a Real gas, ''real'' gas or liquid (as differentiated from an ideal gas) when it is expanding; ty ...

) 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 four 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

External links

*{{Commonscatinline, Cryoneurolysis Neurology procedures Cryobiology