Developing Improved Translational Models of Pain: A Role for the Behavioral Scientist

Abstract

The effective management of pain is a longstanding public health concern. Although opioids have been frontline analgesics for decades, they also have wellknown undesirable effects that limit their clinical utility, such as abuse liability and respiratory depression. The failure to develop better analgesics has, in some ways, contributed to the escalating opioid epidemic that has claimed tens of thousands of lives and has cost hundreds of billions of dollars in health-care expenses. A paradigm shift is needed in the pharmacotherapy of pain management that will require extensive efforts throughout biomedical science. The purpose of the present review is to highlight the critical role of the behavioral scientist to devise improved translational models of pain for drug development. Despite high heterogeneity of painful conditions that involve cortical-dependent pain processing, current models often feature an overreliance on simple reflex-based measures and an emphasis on the absence, rather than presence, of behavior as evidence of analgesic efficacy. Novel approaches should focus on the restoration of operant and other CNS-mediated behavior under painful conditions.

Current Methods to Investigate Nociception and Pain in Zebrafish

“…Even though both larvae and adult zebrafish have been applied to study nociception, further research is required how the response to noxious stimuli might change during development and which methods are best suited for a certain developmental stage. This data would also be important to gauge how well findings from larvae studies would translate to adult fish or even to humans, a prerequisite before screening efforts are wasted ( Mogil, 2019 ; Withey et al, 2020 ). In addition, it has to be considered that employing zebrafish larvae in pain models equals acknowledging their capacity for pain and even though most countries do not have legal protection for these early stages of development, it would be unethical denying them improved refinement in form of analgesics or otherwise when possible ( Sneddon, 2018 ; Kelly and Benson, 2020 ).…”

Unraveling the parameters and biological mechanisms of CO2 laser therapy for acute pain relief

“…Pain is an afflictive experience that is characterized as "An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage" (2). While opioids have long been considered frontline analgesics, their utility is limited due to undesirable side effects such as respiratory depression and abuse liability (3). Therefore, there remains a pressing need to identify alternative, less harmful approaches to pain relief.…”