Placebo-induced analgesia in an operant pain model in rats

College of Dentistry, Department of Orthodontics, University of Florida, Gainesville, FL, USA.
Pain (Impact Factor: 5.21). 08/2012; 153(10):2009-16. DOI: 10.1016/j.pain.2012.04.026
Source: PubMed


Analgesia is particularly susceptible to placebo responses. Recent studies in humans have provided important insights into the neurobiology underlying placebo-induced analgesia. However, human studies provide incomplete mechanistic explanations of placebo analgesia because of limited capacity to use cellular, molecular, and genetic manipulations. To address this shortcoming, this article describes the development of a rat model of conditioned analgesia in an operant pain assay. Specifically, rats were conditioned to associate a placebo manipulation with the analgesic effect of 1mg/kg morphine (subcutaneously) on facial thermal pain. We found that conditioned (placebo) responding bore 3 of the hallmarks of placebo-induced analgesia: (1) strong interanimal variability in the response, (2) suppression by the opiate antagonist naloxone (5mg/kg subcutaneously), and (3) a positive predictive relationship between the unconditioned analgesic effect and the conditioned (placebo) effect. Because of the operant nature of the assay and the use of only a mild noxious thermal stimulus, we suggest that these results provide evidence of placebo-induced analgesia in a preclinical model that utilizes an affective behavioral end point. This finding may provide opportunities for invasive preclinical studies allowing greater understanding of placebo-induced analgesia, thus paving the way for avenues to harness its benefits.

Download full-text


Available from: Robert Caudle, Jul 28, 2014
28 Reads
  • Source
    • "Support for an opioidergic pathway derives from a large body of literature reporting evidence of reversal of placebo analgesia with an opioid antagonist.20 This has been shown in a recent operant rat model based on conditioning of a placebo response21 and human studies22 Based on functional MRI, areas of the central nervous system have been identified which appear to be involved in placebo analgesia in response to rectal distention.23 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Ongoing efforts to improve clinical trial design in irritable bowel syndrome have been hindered by high placebo response rates and ineffective outcome measures. We assessed established strategies to minimize placebo effect as well as the various ap-proaches to placebo effect which can affect trial design. These include genetic markers such as catechol-O-methyltransferase, opioidergic and dopaminergic neurobiologic theory, pre-cebo effect centered on expectancy theory, and side effect unblinding grounded on conditioning theory. We reviewed endpoints used in the study of IBS over the past decade including adequate relief and subjective global relief, emphasizing their weaknesses in fully evaluating the IBS condition, specifically their motility effects based on functional net value and relative benefit-harm based on dropouts due to adverse events. The focus of this review is to highlight ongoing efforts to improve clinical trial design which can lead to better outcomes in a real-world setting.
    Journal of neurogastroenterology and motility 04/2014; 20(2):163-170. DOI:10.5056/jnm.2014.20.2.163 · 2.30 Impact Factor
  • Pain 12/2012; 154(3). DOI:10.1016/j.pain.2012.12.011 · 5.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We present an operant system for the detection of pain in awake, conscious rodents. The Orofacial Pain Assessment Device (OPAD) assesses pain behaviors in a more clinically relevant way by not relying on reflex-based measures of nociception. Food fasted, hairless (or shaved) rodents are placed into a Plexiglas chamber which has two Peltier-based thermodes that can be programmed to any temperature between 7 °C and 60 °C. The rodent is trained to make contact with these in order to access a reward bottle. During a session, a number of behavioral pain outcomes are automatically recorded and saved. These measures include the number of reward bottle activations (licks) and facial contact stimuli (face contacts), but custom measures like the lick/face ratio (total number of licks per session/total number of contacts) can also be created. The stimulus temperature can be set to a single temperature or multiple temperatures within a session. The OPAD is a high-throughput, easy to use operant assay which will lead to better translation of pain research in the future as it includes cortical input instead of relying on spinal reflex-based nociceptive assays.
    Journal of Visualized Experiments 06/2013; DOI:10.3791/50336 · 1.33 Impact Factor
Show more