Translational pain assessment: could natural animal models be the missing link?

Failure of analgesic drugs in clinical development is common. Along with the current "reproducibility crisis" in pain research, this has led some to question the use of animal models. Experimental models tend to comprise genetically homogeneous groups of young, male rodents in restricted and unvarying environments, and pain-producing assays that may not closely mimic the natural condition of interest. In addition, typical experimental outcome measures using thresholds or latencies for withdrawal may not adequately reflect clinical pain phenomena pertinent to human patients. It has been suggested that naturally occurring disease in veterinary patients may provide more valid models for the study of painful disease. Many painful conditions in animals resemble those in people. Like humans, veterinary patients are genetically diverse, often live to old age, and enjoy a complex environment, often the same as their owners. There is increasing interest in the development and validation of outcome measures for detecting pain in veterinary patients; these include objective (eg, locomotor activity monitoring, kinetic evaluation, quantitative sensory testing, and bioimaging) and subjective (eg, pain scales and quality of life scales) measures. Veterinary subject diversity, pathophysiological similarities to humans, and diverse outcome measures could yield better generalizability of findings and improved translation potential, potentially benefiting both humans and animals. The Comparative Oncology Trial Consortium in dogs has pawed the way for translational research, surmounting the challenges inherent in veterinary clinical trials. This review describes numerous conditions similarly applicable to pain research, with potential mutual benefits for human and veterinary clinicians, and their respective patients.