Animal models of pain: progress and challenges

• Published in: Nature reviews. Neuroscience Vol. 10; no. 4; pp. 283 - 294
• Main Author: Mogil, Jeffrey S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2009; Nature Publishing Group
• Subjects: Analgesics; Animal Genetics and Genomics; Animal models in research; Animals; Animals, Genetically Modified; Behavioral Sciences; Biological and medical sciences; Biological Techniques; Biomarkers; Biomedical and Life Sciences; Biomedicine; Brain Ischemia - physiopathology; Disease Models, Animal; Drug dosages; Drug therapy; Evolution, Molecular; Fundamental and applied biological sciences. Psychology; General aspects. Methods; Health aspects; Humans; Laboratory animals; Medical research; Medical sciences; Models, Animal; Neurobiology; Neurosciences; Pain; Pain - pathology; Pain - physiopathology; Pain Measurement - standards; review-article; Risk factors; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Toxicology; Transgenic animals; Vertebrates: nervous system and sense organs; Canada; Animal model; Pain; Sex; Genotype; Review; Communication; Complexity
• ISSN: 1471-003X; 1471-0048; 1471-0048; 1469-3178
• DOI: 10.1038/nrn2606

Key Points Animal models of pain are crucially important for progress in the field, but the poor translation record of pain research has led to a re-evaluation of the appropriateness of current models. The accuracy and relevance of data obtained using current animal pain assays can be improved by choosing subjects and conditions that have more in common, epidemiologically and contextually, with pain patients: both sexes, multiple strains, a wider age range, and with attention paid to social factors. Pain assays have been developed in four successive and overlapping 'waves': acute assays, inflammatory assays, neuropathic assays and the modelling of diseases featuring pain. Current animal models of pain are overly reliant on innate reflexes as dependent measures. Recently developed operant assays may provide a superior alternative. Pain researchers seriously under-study spontaneous pain, and are overly reliant on the measurement of hypersensitivity states. A consensus as to which spontaneously emitted behaviours truly reflect pain in laboratory rodents is sorely needed. Current animal studies of pain largely neglect to measure complex states comorbid with, affected by, and/or contributing to pain. Difficulties in translating basic research findings into safe and effective analgesics have called into question the usefulness of current animal models of pain. Jeffrey Mogil discusses the factors that must be considered when selecting subjects, assays and measures for pain studies. Many are frustrated with the lack of translational progress in the pain field, in which huge gains in basic science knowledge obtained using animal models have not led to the development of many new clinically effective compounds. A careful re-examination of animal models of pain is therefore warranted. Pain researchers now have at their disposal a much wider range of mutant animals to study, assays that more closely resemble clinical pain states, and dependent measures beyond simple reflexive withdrawal. However, the complexity of the phenomenon of pain has made it difficult to assess the true value of these advances. In addition, pain studies are importantly affected by a wide range of modulatory factors, including sex, genotype and social communication, all of which must be taken into account when using an animal model.