Detection of Neuropathic Pain in a Rat Model of Peripheral Nerve Injury

Abstract

Background Behavioral criteria that confirm neuropathic pain in animal injury models are undefined. Therefore, the authors sought clinically relevant measures that distinguish pain behavior of rats with peripheral nerve injury from those with sham injury. Methods The authors examined mechanical and thermal sensory sensitivity, comparing responses at baseline to responses after spinal nerve ligation (SNL group), sham nerve injury (sham group), or skin incision alone (control group). Results Substantial variance was evident in all sensory tests at baseline. After surgery, tests using brush, cold, or heat stimulation showed minimal distinctions between surgical groups. Postsurgical thresholds for flexion withdrawal from mechanical stimulation with von Frey fibers were decreased bilaterally in SNL and sham groups. In contrast, the probability of a complex hyperalgesia-type response with prolonged elevation, shaking, or licking of the paw was selectively increased on the ipsilateral side in the SNL group. Nonetheless, the effect of SNL on behavior was inconsistent, regardless of the sensory test. The behavioral measure that best distinguishes between SNL and sham groups and thereby best identifies animals with successful SNL-induced neuropathic pain is increased ipsilateral postsurgical probability of a hyperalgesia-type response to noxious mechanical stimulation. Using receiver operating characteristics analysis, mechanical hyperalgesia identifies a local SNL effect in approximately 60% of animals when specificity is required to be 90% or higher. Conclusions Simple withdrawal from von Frey tactile stimulation, although frequently used, is not a valid measure of peripheral nerve injury pain in rats, whereas a complex hyperalgesic-type response is a specific neuropathy-induced behavior.