A Closer Look at Neuroma in Pigs and Sex-Specific Pain Responses

At the forefront of translational large-animal research, our team has developed clinically relevant pig models to study nerve injury and pain. Recently, Dr. Sigal Meilin presented on our peripheral neuroma pig model at the International Congress on Neuropathic Pain 2025, highlighting innovative approaches that strengthen translational relevance in preclinical research.

Preclinical research on peripheral nerve injury and repair has primarily focused on rodent models, with limited studies in larger animals. However, a suitable large-animal model is crucial for the translational evaluation of new technologies. Göttingen Minipigs (GMP) were selected due to their physiological similarity to humans in terms of peripheral nerve structure, function, and repair, their acceptability in toxicological studies, and their suitability for long-term follow-up due to slower growth rates.

This model was established in Göttingen minipigs by creating a peroneal neuroma. In this model, the peroneal nerve is cut, and the neuroma develops over several months, with the onset of gradual pain. Both male and female animals were studied to examine potential sex differences in response to injury. In response to von Frey stimulation, there was no difference between males and females. Sensitivity develops quickly but resolves over time, demonstrating a reversible phenomenon. In contrast, thermal sensitivity shows clear sex differences: females are more sensitive, and this heightened response lasts longer and is more persistent than tactile allodynia.

Ensuring normal locomotor activity was important to confirm that animals could walk and withdraw from stimuli appropriately. To assess this, pigs were placed in a 3 × 3 meter arena and their movement was tracked for five minutes. Unlike rodents, pigs covered the entire arena, providing a robust measure of locomotor behavior. Over time, animals initially reduced their walking distance but gradually returned to normal after approximately six weeks, demonstrating that they retained the ability to move and respond to tactile or thermal stimuli.

Behavioral scores reflecting pain levels revealed additional sex differences. Higher scores indicated greater pain, and males tended to show a longer period of altered behavior, while females recovered more quickly. Differences were also observed in the types of behaviors monitored, depending on the sex of the animal, the parameter measured, and the day of measurement. Body weight changes provided another important measure: while normal animals gained weight rapidly, those undergoing neuroma surgery gained weight more slowly. This effect was particularly pronounced in females, although it was also observed in males.

Overall, this model allowed us to evaluate different neuroma treatments for both nerve repair and pain while accounting for sex-specific differences and clinically relevant behavioral and physiological endpoints.

View the poster here.

Watch the recording here.