Differential behavioral outcomes in the sciatic cryoneurolysis model of neuropathic pain in rats

Abstract

We have previously introduced a novel animal model of neuropathic pain in rats following a peripheral mononeuropathy produced by freezing the common sciatic nerve, a technique termed sciatic cryoneurolysis (SCN). In this study, we have further characterized the temporal pattern of behavioral changes following SCN, including thermal hyperalgesia and mechanical allodynia. These behaviors were assessed using noxious thermal (radiant heat) and non-noxious tactile (von Frey filament) stimuli, respectively. Following unilateral SCN, animals exhibited significant ( P < 0.001) bilateral tactile hypersensitivity (allodynia) that persisted at least 10 weeks. However, this lesion did not result in thermal hypersensitivity (hyperalgesia). In fact, thermal sensitivity in the operated limb remained significantly suppressed throughout the 10 weeks ( P < 0.001). Furthermore, we observed autotomy in 76% of SCN-lesioned animals as well as transient weight loss and pale eye syndrome (PES), a phenomenon previously unreported in other neuropathic pain models. PES is a sustained, visibly distinct pallor of the normally pink eye color of the albino rat. We believe PES is a putative marker of heightened sympathetic efferent activity. The severity of autotomy following SCN correlated significantly with both weight loss ( P < 0.001) and the expression of PES ( P < 0.001). Autotomy behavior preceded the onset of allodynia; however, there was no correlation between the severity of expression of these behaviors. These behavioral sequelae are comparable to those seen in other animal models of neuropathic pain, but differ in respect to the increased frequency of autotomy and the lack of thermal hyperalgesia. Our findings support the hypothesis of a sensory basis for autotomy and provide further evidence of central sensitization or disinhibition as the basis for allodynia following peripheral nerve injury. However, the results also indicate independence between the genesis of autotomy and allodynia in animal pain models. The manifestation of sustained allodynia following SCN indicates that this model yields behavioral sequelae similar to those seen in neuropathic pain syndromes in humans.