Alternative models for pain research: A translational, non-mammalian model with an ethical advantage

The use of analgesic drugs to provide relief from pain is one of the most heralded accomplishments of modern pharmacotherapy. However, there is still a great need for testing newer and potentially better analgesic agents using animal models. While the vast majority of pain research is done using mammalian models, primarily rodent species, this chapter briefly reviews the ethical issues as they pertain to non-mammalian pain models and summarizes the alternative models in use. An amphibian pain model that uses dilute acetic acid as the noxious stimulus developed by the author is described in greater detail. Data on the efficacy of opioid analgesics agents shows that the amphibian model has robust predictability for opioid testing and translates into analgesic efficacy in the clinic. Additionally, cloning of opioid receptors from amphibians and other non-mammalian species led to novel hypotheses on the evolution of opioid receptors. The amphibian model has been in use for the past twenty-five years and was developed as an adjunct or alternative animal model for the assessment of opioid analgesia.