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Modern cryoneurolysis is based upon controlled cooling via the expansion of highly pressurized and compressed gas (nitrous oxide or carbon dioxide) through a narrow slit aperture. Gas under high pressure (650-800 psig) passes between the two tubes and is released through a small orifice into the chamber of the tip of the probe. Compressed gas expands as it passes through the orifice, resulting in a rapid decrease in temperature at the probe tip (the Joule-Thomson effect). Absorption of heat from the surrounding tissues accompanies gas expansion and leads to the formation of an ice ball by freezing of intracellular and extracellular water.  The rapid cooling at the tip results in temperatures of approximately -70C. Ice balls vary in size as a function of probe size, freeze time, tissue permeability to water and the presence of vascular "heat sinks." Modern cryoprobes develop ice balls . Modern insulated cryoprobes and cryotherapy units have the ability for discriminative stimulation of sensory and motor nerves. Locating the precise "pain generator" with nerve stimulation is necessary because of the size of the ice ball that is generated and the need to avoid freezing of other nontargeted tissues and nerves.

Therefore, chronic painful conditions due to small localized lesions of peripheral nerves are usual indications for cryoneurolysis.