A direct comparison of affective pain processing underlying two traditional pain modalities in rodents

In the preclinical study of pain, two commonly used pain models are the L5 spinal nerve ligation (SNL) and the injection of carrageenan. Using a modified place escape/avoidance paradigm (mPEAP), a novel behavioral test that quantifies aversive behavior evoked by painful stimuli, we directly compared the affective component of the SNL and inflammation models. Fifty three Sprague-Dawley rats underwent baseline mechanical paw withdrawal threshold (MPWT) and mPEAP testing followed by an L5 SNL or sham surgery for the left paw and then a carrageenan or saline injection for the right paw. After recovering, animals underwent post-manipulation MPWT and mPEAP tests. Both pain conditions produced mechanical hypersensitivity, and animals with a single-paw condition demonstrated escape/avoidance behavior in response to stimulation of the affected paw. Animals with the bilateral pain condition did not show a preference for stimulation of one paw versus the other paw, and the avoidance behavior was not significantly different from the sham/saline control. The results indicate that the pain models are associated with significant avoidance behavior and that they produce comparable degrees of pain affect. These findings advance the preclinical study of pain by validating the simultaneous utilization of the SNL and inflammation models and will allow future studies that combine pain conditions to more closely resemble clinical conditions.

► The first study to compare pain affect in 2 simultaneously present pain conditions. ► The first study to utilize the modified place escape avoidance paradigm (mPEAP). ► Behavior with 2 simultaneous pain conditions is distinct from behavior with only 1. ► Carrageenan injection and L5 spinal nerve ligation are equally aversive.