Characterization of a neuropathic pain model: sciatic cryoneurolysis in the rat

Abstract

Cryoanalgesia, the technique of freezing peripheral nerves, is used clinically for the treatment of postoperative and chronic pain. Paradoxically, this same technique produces characteristics in a rat model suggestive of neuropathic pain. We have developed a peripheral neuropathy model by freezing the proximal sciaticnerve (sciatic cryoneurolysis, SCN) using a cryoprobe cooled to −60°C in a 30/5/30 sec freeze-thaw-freeze sequence. Each freeze cycle produced a transient ice ball on the surface of the nerve. These studies provide behavioral evidence that SCN is a valid mononeuropathy animal model. All animals demonstrate some degree of autotomy following SCN. The average onset of autotomy occurs 4 days postopcratively and peaks in severity and incidence at 14 days. By examining the latency of responses to a noxious heat stimulus, we have shown there is no direct relationship between an hypoesthetic paw and autotomy i.e., autotomy did not occur immediately after the freeze lesion when the limb was dysfunctional. Rather, autotomy peaked when sensation was returning to the affected limb. The transient time course of certain behaviors including hypoesthesia and possible return of limb sensation, autotomy, touch-evoked allodynia, foot edema and the presence of spontaneous noeiceptive behaviors demonstrate a multiple phase nociceptive process. The temporary nature of these nociceptive behaviors is in sharp contrast to the prolonged bilateral mechanical allodynia evident when these behaviors subside. The surgical anesthetics used during the SCN procedure are shown to variably alter or suppress autotomy following SCN. These data support the use of autotomy as an early behavioral marker for neuropathic pain and provide further evidence of the afferent barrage theory following peripheral nerve injury. Experiments using this distinct model may advance our understanding of the neural mechanisms involved in neuropathic pain, while clarifying the clinical safety of cryoneurolysis.