Learned Avoidance From Noxious Mechanical Simulation But Not Threshold Semmes Weinstein Filament Stimulation After Nerve Injury in Rats

Noxious mechanical stimulation evokes a complex and sustained hyperalgesic motor response after peripheral nerve injury that contrasts with a brief and simple withdrawal seen after noxious stimulation in control animals or after threshold punctate mechanical stimulation by the von Frey technique. To test which of these behaviors indicate pain, the aversiveness of the experience associated with each was determined using a passive avoidance test in rats after sciatic nerve ligation (SNL) or skin incision alone. After 18 days, step-down latency was measured during 9 sequential trials at 10-minute intervals. At each trial, rats received either no stimulus, needle stimuli, or threshold Semmes Weinstein (SW) filament stimuli after stepping down. Reactions were either a hyperalgesic response or a brief reflexive withdrawal. In SNL animals, needle stimulation produced substantial learned avoidance when animals showed hyperalgesic responses but produced minimal prolonged latency in SNL animals that showed only simple withdrawal responses. No learned avoidance developed using threshold SW testing in SNL animals. These findings show that needle stimulation is aversive in rats responding with hyperalgesic behavior. In contrast, SW stimulation, as well as needle stimulation that produced mere withdrawal, is minimally aversive. Perspective: The validity of measures of pain in animals is open to question. We demonstrated that needle stimulation is aversive in rats that respond with hyperalgesic-type behavior and is therefore a valid indicator of pain. Stimulation by SW is minimally aversive and is a problematic indicator of pain. Published by Elsevier Inc. on behalf of the American Pain Society