An Animal Model Of Conditioned Placebo Analgesia

Abstract

Research on placebo analgesia (PA) has called for the further elucidation of underlying neural mechanisms. Animal models allow for experimental manipulations that are not possible or feasible in human research such as brain lesions. Therefore, an animal model would be ideally suited to expand upon human PA literature; however, there is currently no animal model of PA. This study used a classical conditioning paradigm in an effort to induce an analgesic response to placebo treatment in rats. Thirty eight female Sprague-Dawley rats underwent an L5 spinal nerve ligation (L5 SNL) to induce a chronic neuropathic pain condition. Animals were conditioned daily for 4 days with subcutaneous injections of saline or active analgesic (gabapentin), then tested for hypersensitivity with a mechanical paw withdrawal threshold test (MPWT). During conditioning, gabapentin effectively attenuated mechanical hypersensitivity as compared with saline controls (p < .001). Following the conditioning period, half of the animals switched treatments on an acquisition day. It was expected that animals conditioned with gabapentin would show a modest attenuation of pain threshold when later administered saline as a placebo, but there was no difference between the gabapentin/saline group and the saline/saline control at acquisition (p > .05). This study revealed crucial information in pursuit of an animal model of conditioned placebo analgesia, most notably the importance of contiguity between the unconditioned stimuli and the unconditioned response.