Animals in Research: A painful conundrum

A recent article in Nature Reviews: Neuroscience by J. Mogil overviews animal models used in different kinds of pain research. (If you don’t have access let juniorprof bring you up to speed on pain research.) The NRN review is motivated by what the author describes as a perception of frustration with the progress made to date in translating seemingly promising research to the human clinical treatment of pain. I don’t know that I’d venture an opinion as to whether success has been good, bad or indifferent in this area- certainly there are many unsolved areas of pain management. Unsolved areas that cause unbelievable distress to individuals with attendant interference with their quality of life and vocational output. Nevertheless, the review puts on a good argument for the body of research using animals that has gone into our current understanding of pain and the ability we have to treat pain. It is worth a read.
Something that is worth discussion without being steeped in the pain research literature arises via a comment to the review that was written by A. D. Craig. [h/t: a reader who may or may not wish to self-identify]
A rat is not a monkey is not a human: comment on Mogil (Nature Rev. Neurosci. 10, 283-294 (2009))

The thesis of this commentary boils down to an assertion that animal models of human pain (or at least a subset of the subjective experiences grouped as pain) are insufficient because of species differences in brain structure and function.

One major reason why pain models in rodents have had little translational success that needs to be added to those mentioned in the article is that — in addition to the numerous genetic and neurochemical differences between rodents and humans, even in the spinal dorsal horn — rats and mice simply do not have the neuroanatomical pathway to the forebrain that is crucial for pain sensation in humans.

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In contrast to the situation for lamina I neurons, which can be studied in rodents (for example, see Ref. 20) because there are strong similarities (and also strong differences!) between rat and primate dorsal horns, the forebrain and the feelings of humans in pain cannot be studied in species that do not have the same neuroanatomical substrates. I submit that these points strongly recommend greater emphasis on studies of pain in humans.

What is fascinating here is that this is an example which would seemingly play right into the hands of the critic of animal research. Aha! Animal research cannot possibly contribute if the circuits are absent! Of course, the situation is complicated and clearly Craig is referring to only one subgroup of the investigations into things we group under the single descriptor of pain. The original review makes the breadth of phenomena and biological contributors to the experiences of pain fairly clear. It is also the case that even Craig refers to the fact that there may be some slight controversy to his substantive points about neurological architecture.
However, if we credit Craig’s points for argument’s sake it leads to another and more general observation about animal models. This passage is particularly striking.

Finally, and perhaps of the utmost significance, the re-representation of this pathway in the anterior insular cortex is crucial for subjective feelings of pain (or any other feeling) in humans and neither rodents nor monkeys seem to have a homologous structure. The inescapable truth is that pain in humans is indeed a subjective experience. The available evidence indicates that neither rodents nor monkeys can experience feelings in the same way that humans do.

One of the points of factual debate* between the animal research and ARA perspectives on the use of animals in research is on the capacity of animals to feel pain. Also the capacity to suffer which, although undefined in most cases, we might assume ties into the type of subjective experience that Craig is trying to delineate from primary tactile experiences of pain. You can think of your favorite points of debate in this area but IME in the more productive versions, the anti-animal research perspective asserts that animals are in “pain and distress” from some particular research protocol. The animal research side (and I am not just talking bull sessions in the cafe; serious investigation goes into making regulation and policy based on these questions) replies with an attempt to define measures that might reflect pain and distress and then to do studies to see if a particular research protocol leads to increases in those measures of pain and distress.
In those cases where the answer comes back “No, we cannot observe anything about this animal that is consistent with an increase in pain and distress”, sometimes the counter-argument is raised that scientists and veterinarians simply do not look at the right measures and there must really still be an increase. Why? Because through the technique of introspection the AR supporter has confidently concluded that what would be painful and/or distressful for him or herself must necessarily be painful and distressful to a rat.
Craig’s commentary seriously questions this confidence. If he is correct in his analysis of the data, it provides a very strong reason for why it is not viable to conclude that human introspection tells us much about the rodent experience of pain.
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*to the extent this every happens