Mechanism research of cryoanalgesia

Abstract

The sciatic nerves of rabbits were frozen at different temperatures (-20 degrees C, -60 degrees C, -100 degrees C, -140 degrees C, and -180 degrees C). The morphology and function of the frozen nerves were examined with light microscopy (hematoxylin and eosinophilin stain and a histochemical thiocholine method) and electron microscopy. The function of the nerve after freezing was assessed using short latency somatosensory evoked potentials, sensory conduction velocity, and electromyogram at various intervals after freezing. There were no changes in morphology or function of nerves cryolesioned at -20 degrees C. The nerve fibers cryolesioned at -60 degrees C showed signs of freezing degeneration and lost their conductive function although, these nerves all recovered. Approximately half of nerve fibers cryolesioned at -100 degrees C showed Wallerian degeneration, and although the time to remyelination was delayed, nerve regeneration was still complete. At -140 degrees C and -180 degrees C the nerve fibers showed immediate necrosis, with destruction of basal membranes and proliferation of collagen fibers. The results explained the mechanism of cryoanalgesia. Our study demonstrates that cryo-temperatures lower than -140 degrees C will cause permanent alterations in nerve morphology and function, whereas warmer temperatures do not result in permanent nerve damage and are therefore not likely to provide long-term analgesia to patients.

Significance of Clinical Treatments on Peripheral Nerve and its Effect on Nerve Regeneration

“…Histological studies have shown that for treatment of nerves with temperatures from -20° to -60°C Wallerian degeneration occurs while leaving the endoneurium intact [53]. Additionally, a comparative study between crush lesion (a common model of Wallerian degeneration) and cryoneuromodulation treatment on a rat sciatic nerve showed comparable histological results of second degree injury [54].…”

Novel cryoneurolysis device for the treatment of sensory and motor peripheral nerves

“…published a 3-point nerve injury scale in 1943 [4], and in 1951, Sir Sydney Sunderland published a 5-point scale which gave more resolution to Seddon's scale (Table 1) [5]. These scales classify nerve injury as a function of temperature [6,7]:…”

“…Cryoneurolysis is the direct application of cold temperatures, resulting in a second-degree injury to the peripheral sensory nerve [7]. Treatment in this temperature range causes a reversible degeneration of the axon beginning at the site of treatment and proceeding distally [8].…”

“…Treatment in this temperature range causes a reversible degeneration of the axon beginning at the site of treatment and proceeding distally [8]. Wallerian degeneration (axonal and myelin degeneration) occurs when the nerve is exposed to temperatures below −20°C [7]. Upon injury, the axon begins a degeneration process at the injury site and progresses distally.…”

“…In contrast, third-, fourth-, and fifth-degree injuries (which occur at temperatures colder than −100°C, transection, or thermal heat lesions) cause irreversible nerve injury, disrupting the acellular nerve structures, and sometimes causing neuroma formation and aberrant axon regeneration [7,23].…”