Fig. 1.

Operant conditioning tests for evaluation of SCI pain. (A) Place-escape avoidance paradigm (PEAP) pits aversion to light against aversion to a putatively noxious stimulus such as tactile, cold, or heat. In this test, the painful stimulus is presented in (for mechanical stimuli) or makes up the flooring of (for thermal stimuli) only the dark side of the chamber, whereas in the light chamber the stimulus is applied to a potentially nonpainful body region or not at all. (B) Increased time spent in the light side of the chamber is indicative of aversion to the sensory stimulus, suggesting that the rat perceived it as being painful [33]. (C) In the Mechanical Conflict Avoidance System, a light chamber is connected to a dark chamber by noxious flooring consisting of spikes that can be raised to different heights. When the light is turned on, the rat crosses the floor to reach the dark chamber. Rats with pain exhibit a longer latency to exit the light chamber and begin crossing the noxious flooring [35]. (D) Conditioned place preference (CPP) testing can also use a light/dark chamber setup [42], or two neutrally lit chambers with distinctive flooring and walls [36]. In conditioning trials, the dark side of the chamber is paired with vehicle administration, whereas the light side of the chamber is paired with administration of a drug that may alleviate pain. Chamber preference is evaluated during a subsequent session when the drug is not administered. (E) Increased time spent in the light side of the chamber indicates that the subject experienced pain relief in response to drug administration