Dr Alexis Gaudin on studying pulpitis on animal models

Iveta Ramonaite, Dental Tribune International

Tue. 19. April 2022

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Dr Alexis Gaudin is an associate professor in the Department of Endodontics at Nantes Université in France. In 2021, together with five other researchers, he published a review article that sought to provide a thorough understanding of the different animal models used in dental research to study pulp inflammation. In this interview with Dental Tribune International, Dr Gaudin discusses the ideal animal model for studying pulpitis, talks about the increasing popularity of non-animal methods in dental research and considers the possibility of studying artificially generated caries-inducing models in the future.

Dr Gaudin, why is it important to choose the most appropriate animal model in dental research, and how would you describe the ideal animal model for studying pulp inflammation?
As in other medical fields, both dental research and the pharmaceutical industry aim to identify therapeutic strategies that can decrease pain, that can make dental therapeutics more efficient, faster and more comfortable, and that can make more predictable results possible. The use of animal models can accurately replicate many oral diseases and dental issues. Their use makes it possible for scientists to conduct research into the effect of new drugs and therapeutic proposals.

The correct choice of an animal model is vital in order to minimise suffering and cost while maximising efficiency and the success of the research. Scientific and practical decisions govern the selection of the animal model. For example, the animal model used must be as close as possible to humans from an anatomical, biological and physiological point of view. The operating conditions for inducing pulpitis, including accessibility and dental dam installation, must be technically simple, and the inflammatory conditions obtained must be equivalent to those found in humans.

The animal model should give the most precise and scientifically interpretable results while presenting the least serious biological risk for the research team. The results should be reproducible, and the animal model should be available and have reasonable acquisition and care costs. The choice should also be directed towards the species requiring the fewest animals. Finally, the research should be conducted on the minimum number of animals to provide the maximum amount of information.

What are some of the hurdles in choosing the correct animal model to study dental pulp?
Among the animal kingdom, rodents, rabbits, ferrets, swine, dogs and non-human primates have been used to model human pulpitis. The diversity of animals found in studies indicates the difficulty of choosing the correct and most efficient model. Each animal model has its own characteristics that may be either advantageous or limiting, depending on the study parameters.

Non-human primate models have certain limitations such as zoonotic risks, supply difficulties and a high cost of purchase and maintenance.

The correct choice of an animal model is vital in order to minimise suffering and cost while maximising efficiency and the success of the research

It is generally accepted that the immune systems of rats and mice are comparable; however, much more information is available for the mouse. Moreover, there are differences between the results obtained in mice and rats. For instance, several studies have shown that the immune parameters in mice are more sensitive to the effects of stress (as measured by corticosterone) compared with those in rats. Even if rodents are the mainstay of in vivo immunological experimentation, it is important to point out that the immune systems of mice/rats and humans are quite similar but also present some differences, especially when it comes to development, activation and response to aggression. It is, therefore, necessary to consider the possibility that a given murine model response may not occur in exactly the same way in humans.

There are higher costs involved with the use of larger animals such as swine and dogs.

How is pulpitis typically induced in animal models?
There are three main dental pulp induction techniques found in the literature, varying according to the causal agent. The first technique consists of making cavities with burs under water spray until pulp exposure. The second method involves creating cavities under the same conditions as previously described, with or without pulp exposure. Once the cavity has been made, an exogenous supply of toxins, such as lipopolysaccharide or human carious dentine, is placed either directly in contact with the pulp or at the bottom of the cavity so that the toxins diffuse through the dentinal tubules.

The third induction technique consists of using transgenic animal models.

What are some of the disadvantages of choosing an animal approach to studying pulpitis?
The use of animal models in research is still debated from an ethical point of view. There is not an ideal animal model since they all have advantages and drawbacks.

In the future, it might be possible to consider artificially generated caries-inducing models

How effective are in vitro experiments and other experimental alternatives for studying pulpitis, and are they gaining increasing popularity in dental research?
Alternative methods are gaining popularity since they are becoming increasingly accurate. They involve 3D experiments and can combine new knowledge to implement the experiment. The overall aim is to limit animal suffering and to protect the welfare of animals.

What changes do you see in dental research on animals in terms of legislation, ethicality and the validity of findings?
The rule of the three Rs was developed by Russel and Burch in 1959 and forms the basis of the regulation and the ethical foundation of the use of animals for scientific purposes. It stands for replacement, refinement and reduction (in the number of animals). More recently, a fourth R, responsibility, was added in order to focus on the integrity and honesty of scientists regarding the proper and reasonable use of laboratory animals. However, legislation differs from country to country.

In your opinion, how will dental pulp be studied in the future? Will there be novel methods that will help researchers better understand the physiology of dental pulp?
In the future, it might be possible to consider artificially generated caries-inducing models that would represent a more elegant and closer-to-reality alternative to mechanical injury and lipopolysaccharide stimulation. This would also help to avoid off-target effects of the transgenic models.

Additionally, biological markers and other novel diagnostic tools could help to successfully visualise pulp morphology, vitality and regeneration.

Editorial note:

More information about the review article can be found here.