Operant Assays for Assessing Pain in Preclinical Rodent Models: Highlights from an Orofacial Assay

Abstract

Despite an immense investment of resources, pain remains at epidemic proportions. Given this, there has been an increased effort toward appraising the process by which new painkillers are developed, focusing specifically on why so few analgesics make it from the benchside to the bedside. The use of behavioral assays and animal modeling for the preclinical stages of analgesic development is being reexamined to determine whether they are truly relevant, meaningful, and predictive. Consequently, there is a strengthening consensus that the traditional reflex-based assays upon which several decades of preclinical pain research has been based are inadequate. Thus, investigators have recently turned to the development of new preclinical assays with improved face, content, and predictive validity. In this regard, operant pain assays show considerable promise, as they are more sensitive, present better validity, and, importantly, better encompass the psychological and affective dimensions of pain that trouble human pain sufferers. Here, we briefly compare and contrast reflex assays with operant assays, and we introduce a particular operant orofacial pain assay used in a variety of experiments to emphasize how operant pain assays can be applied to preclinical studies of pain.

Pain control through selective chemo-axotomy of centrally projecting TRPV1+ sensory neurons

“…Operant behavioral assessments provide outcomes that integrate sensory information with cerebral processing (37)(38)(39)(40). We used orofacial operant behavioral tasks to assess nociceptive sensitivity of rats pretreated with RTX.…”

Effects of cocoa‐enriched diet on orofacial pain in a murine model

“…We have developed operant assessments, such as the OPAD, that better reflect responses predicated on the integration of the nociceptive and central inputs . For a more in‐depth summary of the use of the OPAD in comparison with other pain measures, refer to a review by Murphy et al . The OPAD uses a reward‐conflict paradigm that, unlike for reflex‐based responses, involves assessment of higher‐level cognitive processing, whereby the animal must decide whether it will complete the task to obtain a reward, based on its pain level.…”

“…A bottle containing diluted (1:2 with water) sweetened condensed milk solution was positioned such that access to the reward was possible contingent on facial contact with the thermode. Reward‐licking events and facial‐stimulus‐contact events were recorded . Animals were considered trained (~2 weeks) on the OPAD when they achieved >1 000 licking events with the thermode set at 33°C.…”

Neurobiological studies of chronic pain and analgesia: Rationale and refinements

“…Finally, there is increasing consideration being given to refining pre-clinical assessment of chronic pain to include more affective or motivational aspects of the pain experience; for more discussion of these approaches the reader is referred to two recent, excellent reviews (King and Porreca, 2014;Murphy et al, 2014). In short, more complex behaviors are more frequently assessed in chronic pain models including, but not limited to, locomotor activity, depressed voluntary behaviors (Negus, 2013), facial expressions (Sotocinal et al, 2011), and motivation to pursue analgesics either through the conditioned place preference assay (King et al, 2009) or analgesic self-administration experiments (Gutierrez et al, 2011;Martin and Eisenach, 2001;Martin et al, 2007Martin et al, , 2006.…”