The study of pain and analgesia is an important area of biomedical research which has led to a number of significant advances in the treatment of acute and chronic pain in the clinic. This area of research examines the physiology of pain transmission and the pharmacology of analgesic drugs by employing a variety of in vitro and in vivo animal models. To date, the vast majority of in vivo models for pain research have used mammalian species, primarily rodents and, to a lesser extent, canines, felines, and primates. The present review summarizes the special considerations of animal use in pain research and the philosophic and scientific basis for developing adjunct models using lower vertebrates. Existent literature on pain research using non-mammalian vertebrates is reviewed, with a special focus on amphibian species. Given the ethical concerns of experimental animal use and the importance of a comparative approach to the basic understanding of pain-processing, the further development of non-mammalian models for pain research should be encouraged.