The Use of an FR1 Schedule Operant Approach-Avoidance Paradigm to Measure the Aversiveness of Neuropathic and Inflammatory Pain

Abstract

Pain is a subjective, private, yet universal phenomenon that depends on a unique combination of sensory, affective, and evaluative characteristics. Although preclinical models have been used to understand much of pain physiology, the inability to communicate with animals limits affective and evaluative feedback and has constrained traditional behavioral methods to adequately represent and study the multidimensional pain experience. Therefore, this study sought to characterize the affective component of pain within a novel operant approach-avoidance paradigm (AAP) to determine which type of pain (inflammatory and neuropathic) may be more aversive. To reveal the possible differences in pain aversiveness within the AAP paradigm, animals received bilateral inflammatory and neuropathic pain conditions and were given the choice to a) forgo appetitive reward by not receiving noxious stimulus of either inflammatory or neuropathic conditions or b) receive noxious stimulus in exchange for an appetitive reward. Although all pain conditions produced significant hypersensitivity, the AAP results revealed there was no preference in the stimulation of a specific paw in the bilateral pain conditions. The finding suggests that despite unique clinical pain characteristics for inflammatory and neuropathic conditions, the lack of observable differences in the pain conditions may not necessarily equate to the overall similarity in aversiveness, but rather that the fixed ratio (FR1) paradigm presentation allowed appetitive reward to be more salient, highlighting the complexities of competing motivational drives of pain and hunger when satiating hunger is always guaranteed. Thus, future studies should seek to further tease apart this relationship with a different schedule and food-controlled methodologies. The development of such preclinical approaches can thoroughly investigate the intricacy of competing drives and likely reveal important information regarding the complexity of pain, enhancing our understanding of pain perception in individuals suffering from comorbid pain states.

Keywords: approach; avoidance; inflammation; neuropathy; operant; pain.

Figure 1

The Med Associates Inc. operant chamber used for the approach-avoidance paradigm (AAP), designed with a wire mesh floor and levers located on the left and right sides of the food dispenser. Above each lever is a single stimulus light that serves as a cue to signal the active lever.

Figure 2

Mechanical paw withdrawal threshold (MPWT) by pain conditions for both left and right paws for baseline and test days using mean (±SEM) MWPT score for each condition. The left paw was associated with L5 spinal nerve ligation (SNL) or sham condition. SNL conditions were associated with a significant decrease in withdrawal threshold for test days compared to sham animals. The right paw was associated with carrageenan or saline condition. Carrageenan-treated conditions were associated with a significant decrease in the withdrawal threshold for test days compared to saline animals. *p < 0.001.

Figure 3

Percent success (±SEM) in lever-pressing for left and right levers and pooled left and right omissions across pain conditions for baseline (A) and test days (B). Success rates were quantified by using an individual number of lever-presses for the paradigm on test day and dividing by the total number of trials for each side (30). There were no differences in success rates for lever-pressing or omissions to the AAP.

Figure 4

Average latency in seconds (±SEM) to respond to the lever by pressing for the appetitive reward for left and right levers across baseline (A) and test days (B). There were no differences in latency to lever-press across conditions in the AAP.