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, axonotmesis and neurotmesis) and degrees of nerve injury that occur as a result of exposure to various temperatures.
Cryoneurolysis treatments that use nitrous oxide (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, with Wallerian degeneration occurring distal to the site of injury. The axon and myelin sheath are affected, but all of the connective tissues (endoneurium, perineurium, 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 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.