Axonal viability and the persistence of thermal hyperalgesia after partial freeze lesions of nerve

Partial freeze injuries of rat sciatic nerve have been used to investigate the relationship between the amount of tissue injured and the magnitude and duration of the resulting thermal hyperalgesia. Complete freeze injury of peripheral nerve produces temporary anesthesia to peripheral stimuli and is a useful neurolytic technique. The present study examined the hypothesis that incomplete nerve lesions, in which some fibers survive while others undergo Wallerian (axonal) degeneration, lead to development of thermal hyperalgesia. In this study, performed on rats, one sciatic nerve was frozen with a cryoprobe (-60 degrees C) for periods ranging from 2 to 60 s. The behavioral response to thermal stimulation of the hind footpad was tested pre- and postoperatively at days 3, 5, 7, 9, 13, 15, 19, 22, 26, and 32. In separate, groups of animals with similar lesions, nerves were removed and processed for electron microscopy. Light and electron microscopy were used to determine the nature of injury to nerve fibers and its extent. There was a direct relationship between the duration of the freeze lesion and: (1) the number of nerve fibers injured; and (2) the magnitude of the resulting Wallerian degeneration. Following partial sciatic nerve injury with axonal degeneration, hyperalgesia developed within several days, peaked at approximately 1 week postinjury, and resolved during the next several weeks. Both the magnitude of the hyperalgesic response and its persistence were directly related to the duration of the freeze lesion, except in those animals in which all nerve fibers were damaged. These animals were anesthetic to thermal stimulation of the experimental footpad. This relationship helps explain the pathogenesis of painful syndromes associated with failed cryoneurolysis and may be useful in itself as a model of neuropathic pain.