How does animal research benefit humans?
Why animals are used to study pain
Research using animal models has provided invaluable insights into human health and disease, including advancements in our understanding of pain. Animal models help uncover fundamental biological processes, identify novel therapeutic targets and disease mechanisms, and model specific aspects of disease progression. Additionally, they are often required for safety and toxicology studies of potential new drugs before human clinical trials.
A wide range of species in pain studies
Animals across the evolutionary spectrum, from fruit flies (Drosophila) and zebrafish to rodents, dogs, and non-human primates, have contributed to different aspects of pain research. For example, Drosophila larvae have been used in genetic screens to identify genes involved in detecting noxious stimuli. Some dogs naturally develop osteoarthritis, and pain-relieving treatments developed for them have the potential to be adapted for human use. However, rodents—specifically mice and rats—are the primary species used in preclinical pain research. Their physiological and neuroanatomical similarities to humans, susceptibility to comparable diseases, low cost of maintenance, rapid breeding cycles, and short gestation periods make them ideal models. The rise of transgenic technologies, including optogenetics and chemogenetics, has further increased the importance of mice as a model organism for pain research.
What rodents teach us about pain
Rodent models have significantly advanced sensory neuroscience and pain research. They have helped map complex neuroanatomical pathways from peripheral tissues (e.g., the foot or stomach) to the spinal cord and brain. Additionally, rodent studies have identified key ion channels, receptors, and cell types that contribute to pain processing. Understanding these mechanisms lays the groundwork for developing new, non-opioid pain treatments. While cell culture, induced pluripotent stem cells, and organoids are important tools, they lack the complete physiological and behavioral complexity necessary to study pain and other complex disease mechanisms.
Are animal models still useful?
The limited development of new pain drugs over the past two decades has led to questions about the relevance of animal models. However, combining clinical data with findings from animal research provides a powerful strategy for discovering new therapeutic targets. Below are several examples that have led to a positive clinical impact. Calcitonin gene-related peptide (CGRP) antagonists for migraine and Nav1.8 sodium channel inhibitors for neuropathic pain are among the few new pain drugs approved in recent decades. Their development combined clinical observations, such as elevated CGRP levels in migraine patients or pain-related mutations in Nav1.8, with mechanistic studies in animal models. These models were essential for understanding how these molecules contribute to pain, providing the rationale for drug development.
When animal research leads to new treatments
The development of disease-modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis has used several animal models and has resulted in many successful drugs. While DMARDs were originally developed to reduce joint destruction in rheumatoid arthritis, they have also proven effective in alleviating arthritis-associated pain, which is the most common complain of rheumatoid arthritis patients. Rodent models played a crucial role in identifying the involvement of TNF, IL-1β, JAK/STAT signaling, and specific autoantibodies in both disease progression and pain. They are now all targets of DMARDs, which reduce rheumatoid arthritis and often improve pain.
New discoveries about fibromyalgia from mice
Mouse models have also helped identify novel mechanisms underlying fibromyalgia-associated pain. First, a role for pain-inducing antibodies in fibromyalgia was identified by transferring antibodies from fibromyalgia patients or pain-free controls into mice. The fibromyalgia antibodies, but not the control antibodies, cause mice to develop pain-like behaviour. This finding has potential implications for developing diagnostic tests and immunomodulatory treatments for fibromyalgia. Another study at McGill University showed that fibromyalgia patients have an altered gut microbiome. To test its causal role in pain, researchers transplanted the gut microbiota of fibromyalgia patients into germ-free mice. These mice developed pain-like behaviors, while those receiving microbiota from pain-free controls did not. This discovery provided the rationale for a pilot clinical trial, which found that fecal microbiota transfer from healthy donors improved fibromyalgia symptoms.
Looking ahead: animals still play a key role
Animal models remain an essential component of pain research, offering insights that cannot be obtained from human studies alone. While no model is perfect, combining animal research with clinical data enhances our ability to uncover disease mechanisms and develop effective treatments. Leveraging these models alongside human-based research will further our understanding of pain mechanisms and ultimately improve patient care.
References
Leung, C., Yana, W., M., K. T. & and Neely, G. G. Fruit Flies as a Powerful Model to Drive or Validate Pain Genomics Efforts.
Watkins, L. R. et al. Targeted interleukin-10 plasmid DNA therapy in the treatment of osteoarthritis: Toxicology and pain efficacy assessments.
Sadler, K. E., Mogil, J. S. & Stucky, C. L. Innovations and advances in modelling and measuring pain in animals.
Krock, E., Jurczak, A. & Svensson, C. I. Pain pathogenesis in rheumatoid arthritis-what have we learned from animal models?
Krock, E. et al. Fibromyalgia patients with high levels of anti-satellite glia cell IgG antibodies present with more severe symptoms.
Goebel, A. et al. Passive transfer of fibromyalgia symptoms from patients to mice.
Minerbi, A. et al. Altered microbiome composition in individuals with fibromyalgia.
Cai, W. et al. Gut microbiota promotes pain in fibromyalgia.
