Inspiration Corner: Embrace the 3Rs

Food for Thought: Monitoring and Reporting Post-Operative Pain in Rodent Models
Author: Annemarie Lang, DVM, PhD, Assistant Professor, Department of Orthopaedic Surgery, University of Michigan

Monitoring and accurately reporting post-operative pain in rodent studies remains a major challenge across biomedical research, and our field is no exception. Whether working with bone fracture models, vertebral injury models, OVX models, or mechanically induced osteoarthritis, we routinely operate within moderate-severity experimental frameworks that inherently involve perioperative pain. Yet the way this pain is measured, interpreted, and reported varies widely, making it difficult to compare studies, reproduce findings, or ensure that our models reflect clinically meaningful recovery trajectories.

A recent systematic review of post-operative pain models offers valuable insights with direct relevance to orthopedic and musculoskeletal research. By analyzing 674 preclinical studies, the authors highlighted persistent gaps in model choice, outcome measures, sex inclusion, methodological rigor, and reporting practices, issues that mirror patterns we also see in our own domain.

This review underscores an important message for our community:
Improving how we measure, manage, and report post-operative pain is not simply a matter of refinement, it is foundational to enhancing the translational relevance of our models.

Key Implications for Our Field

• Pain outcomes must reflect functional recovery. Heavy reliance on mechanical hypersensitivity overlooks non-evoked and movement-evoked pain, which are highly relevant for orthopedic models.
• Moderate-severity models demand clearer reporting. Details such as surgical regimens, housing conditions, enrichment, and experimenter sex remain underreported across fields but are especially critical in models involving tissue injury or bone healing.
• Sex-bias persists. With 83% of reviewed studies using only males, the review highlights a gap that also affects many orthopedic pain models.
• Rigor matters. Underuse of randomization, blinding, and sample-size justification contributes to variability and weakens translational impact.

Why This Matters

As a community working on injury- and degeneration-related pain, we rely heavily on robust and ethically optimized models. This systematic review serves as a reminder, and an opportunity, to reflect on our own practices. By adopting the recommended “minimum translational set,” we can improve reproducibility, strengthen our science, and better align our models with the complex reality of clinical perioperative pain.

Reference: Segelcke D, Jolmes J, Pradier B, Rosenberger DC, Macháček PA, Bakker R, Ritte A, Kartscher A, Graw C, Jurr H, Rosenbusch J, Ellerbrock M, Alnekitty N, Baumann L, Weseloh R, Oymak E, Schaefer CM, Sondermann JR, Schmidt M, Tappe-Theodor A, Hestehave S, Jirkof P, Zahn PK, Vollert J, Soliman N, Collazo A, Kniffert S, Pogatzki-Zahn EM. Systematic review and quantitative trend analysis of scientific quality in preclinical studies using rodent models of post-surgical pain. Neurosci Biobehav Rev. 2025 Dec;179:106422. doi: 10.1016/j.neubiorev.2025.106422. Epub 2025 Oct 20. PMID: 41115489.

Social Buffering for Stress Reduction in Rodents
Author: Kait Link, DVM, Wu Tsai Human Performance Alliance, University of Oregon

Alongside physical enrichment, social context plays a crucial role in rodent welfare. In their 2022 paper, Denommé and Mason highlight the use of social buffering as a powerful tool for improving rodent welfare. Social buffering refers to the phenomenon in which the presence of conspecifics reduces stress responses, thereby mitigating the impact of potentially aversive events. This mechanism operates through several pathways, including affiliative social contact, emotional contagion, distraction, comfort, and safety cues. Importantly, calm or bonded companions tend to provide the most effective buffering, whereas the presence of distressed associates can sometimes exacerbate negative outcomes.

In rodents, social buffering has been shown to lessen fear, pain, and stress reactions. The presence of companions can lead to lower corticosterone levels, faster wound healing, and greater resilience to common stressors such as handling, restraint, or cage cleaning. These benefits underscore the welfare costs of acute isolation and reinforce the importance of social housing as a baseline standard of care. While most animal welfare programs already mandate social housing for rodents, Denommé and Mason emphasize that buffering can be extended beyond housing conditions. For example, providing companions, or even indirect substitutes such as familiar odors, synthetic fur, or social cues, during stressful husbandry or research procedures can significantly reduce distress, yet this approach is not widely implemented across institutions.

The effects of social buffering are not uniform and may vary with species, strain, sex, age, the quality of the social relationship, and the intensity of the stressor. This variability highlights the importance of careful consideration when designing welfare strategies. Nevertheless, the weight of the evidence supports integrating social buffering into both housing and procedural planning. By integrating social buffering strategies with enrichment programs, research facilities can reduce stress, enhance well-being, and improve the reliability of scientific outcomes.

Reference: Denommé MR, Mason GJ. Social Buffering as a Tool for Improving Rodent Welfare. J Am Assoc Lab Anim Sci. 2022 Jan 1;61(1):5-14. doi: 10.30802/AALAS-JAALAS-21-000006. Epub 2021 Dec 16. PMID: 34915978; PMCID: PMC8786379.