The added value of pathology in animal experiments

To help doctor/researcher Elise Brakkee (Plastic Surgery, UMC Utrecht) with her research on an effective treatment for neuralgia in humans, the Animal Welfare Body Utrecht put her in touch with veterinary pathologist Judith van den Brand (Veterinary Medicine, Utrecht University). We spoke with the two of them about their fruitful collaboration.

What was the reason for you to work together?

Van den Brand: “Pathology often doesn’t play a big enough part in animal experiments, and some-times not until quite a late stage in the game, even the point where the experiments are finished and the materials are already in jars. That’s why we at Veterinary Medicine started a pilot together with the AWB, so we can help the researchers plan their project early in the process, and look at the proposal together.”

Brakkee: “Since I’m setting up my study on my own, it’s important that I draw on as much expert knowledge as possible. I look at who has the necessary expertise and who can help me with each part of my study. You need to do animal experiments to find the cause of neuralgia and to test pos-sible new treatments. When I submitted my project proposal to the IvD (Animal Welfare Body Utrecht, ed.), they recommended I talk with Judith so I could get even more useful information out of my research.”

“If the basis of animal testing isn’t good, you can overlook things”

Van den Brand: “I use my expertise to advise researchers on how to get the most information pos-sible from the lab animals they’re using. Making optimal use of animal pathology is part of good re-search. I look from a pathologist’s perspective to see what additional research method might be suitable for the study. As pathologists we’re not doing this with the goal of ticking all the boxes our-selves: we don’t take over anybody’s work, but we like to get involved in the process thinking about what else you might find, and what additional aspects could be important. Our aim is to help the researchers take the quality to a higher level, which will give the research greater impact.”

“The way pathological research is done is very structured and specialised. You always look first at the tissue from the outside. Then you look at it under the microscope using the normal H&E (hema-toxylin and eosin, ed.) stain. After that you use any additional stains to study particular details. Since many researchers are focused on just one facet in their research, they don’t always use the structured method that pathologists are supposed to use. Then they’re not looking at the big picture, and they can miss something important.”

Brakkee: “My research involves initiating a neuroma – a growth in the nerve tissue – in one leg of a mouse. A neuroma causes some pain, and we’re looking at new therapies to eliminate that pain.”

Van den Brand: “The basic setup of research like this is very important. If it’s not good from the start, the outcomes may not produce the desired results.”

What does your working relationship look like?

Brakkee: “Our collaboration mainly consists of me getting advice from Judith. Since I wanted to stain a neuroma for microscopic research, the question was how I could do that with a mouse or rat. Initially, I was going to surgically cut out only the neuroma from the dead animal, but when I consulted Judith and her colleagues, they suggested I fix the whole leg and examine it. That way you can study how a neuroma interacts with its environment, for example, how it’s grown into the surrounding tissues.”

Brakkee: “We remove other tissues besides the neuroma: the sciatic nerve, the spinal cord, and the large cell body next to the spinal cord, that says something about sensory abilities. What’s new is the way we cut and stain a neuroma.”

What is your wish?

Brakkee: “We want the collaboration to enable us to get as much information as we can from the lab animals. In my situation, that means information that has some bearing on finding an effective treatment for neuralgia. We can publish articles about the insights we’ve gained, and in the long term we’ll be using these insights to treat people.”

Van den Brand: “Exactly what Elise said. The goal is to advise researchers that, if they’re intending to use laboratory animals in their research, they should really ask themselves how they’re going to use them. And if they really are going to use all the opportunities that presents. A veterinary pathologist is a specialised veterinarian who uses knowledge of veterinary medicine and veterinary pathology to help researchers from all kinds of backgrounds look at the big picture and set up their studies correctly and in a structured way. That also applies to researchers in human medicine. We’re also used to working with a range of animal species. That knowledge can be important when translating information from animals to humans.”

And what comes after the pilot?

Van den Brand: “There are only a few people specialised in animal pathology. I‘d like it if we could join forces, perhaps in the form of a platform, and within that we could also work with human pathologists. Second: giving advice in animal experiments is something we’re doing as a pilot in addition to our regular work, but to be able to keep on doing it, we’ll have to look at ways to fund it.”

Would you also like advice from a veterinary pathologist?

You can get it even before you write a project proposal or work protocol. Ask us about it.

Judith van den Brand is a veterinary pathologist and a member of the faculty of Veterinary Medi-cine. She works in research, diagnostics and teaching. She received her PhD at the Erasmus Med-ical Centre and does research on zoonotic viruses, such as SARS, MERS, and the new Corona-virus (COVID-19).

Elise Brakkee is a doctor-researcher with the Plastic Surgery department of the UMC Utrecht. She researches neuropathic pain (neuralgia) caused by nerve damage and neuroma growth. She hopes that animal experiments will help her to discover what causes neuralgia and what treatment works best.