Classify as category D or E? Does it matter to the rats or to USDA? No. For any given manipulation of the rats, the pain category classification will have no impact on them whatsoever. The USDA regulations exclude rats of the genus Rattus that are bred for research. So we can assume that the IACUC's policy is simply to apply the same requirements to all species—a laudable, even if unnecessary, goal.
It matters not whether pain is artificially provoked or unprovoked; it is pain either way. Whether hypersensitivity to cold or heat is painful could be argued, depending on degree of the cold or heat, the duration of exposure and the ability of the animal to freely move away from the source of the cold or heat. Given that at Subaraman's former institution, only the animals that experienced clinical neuropathy were placed in category E, we can assume that the hypersensitivity, and its detection, in this case does not involve more than slight or momentary discomfort—that is, it is not significant.
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