I suppose it has been a topic that researchers have wondered about over the years, as they pray over the latest results of the experiment that has to work so they can get that next chunk of grant money; but it has not been shown that human presence can affect the results of laboratory experiments.

Until now.

Researchers reporting in the April 28th online edition of Nature Methods describe producing pain in mice by administering ankle injections of an inflammatory agent, and placing these otherwise experimentally naïve mice into clear Plexiglas cubicles—this allowing for the observation and recording of facial expressions of pain. Using the Mouse Grimace Scale, the researchers were able to compare facial grimacing in mice tested in the presence of an experimenter to that of mice tested in an empty room.

It was found that four different male experimenters produced robust and significant decreases in facial grimacing relative to no observer; in contrast, none of the four adult female experimenters produced significant changes in facial grimacing. Both male and female mice displayed the ‘male observer’ effect, but it was displayed to a much greater degree by the female mice. This phenomenon appeared to the authors of the report to be olfactory in nature, as the same degree of grimacing was noted if T-shirts worn the night before by male or female experimenters were placed in close proximity to the mice: While the male-worn T-shirt produced the maximal pain-relieving effect, it was abolished by the simultaneous presence of a female-worn T-shirt. Chemicals from underarm secretions appear responsible (other pheromones or novel food smells had no impact).

Interestingly, bedding material from unfamiliar male mice, nonpredator male guinea pigs and rats, cats, and dogs, all produced decreases in facial grimacing when mice were exposed to these. However, bedding from castrated male mice, cats and dogs did not produce the effect—suggesting the necessity of male hormones to decrease facial grimacing.

The researchers provide possible explanations for the decrease in pain behaviors observed:

• Mice might be consciously inhibiting outward signs of pain, so as not to appear weak in the presence of potentially aggressive males.

• The stimuli might be producing stress-induced analgesia, the innate response whereby the processing of pain is inhibited in the spinal cord by signals sent down by the brain. (Prior research had shown that predator odors and odors of males of the same species also produce stress-induced analgesia.)

The pain-dampening effect of stress can have a painful effect on the study of pain: Such reactions affect the rodents’ behavior and potentially confound the results of animal studies, the study suggests. How should experimenters address this potentially powerful confounding factor? At the very least, researchers should report the gender of experimenters in their publications, and if the experimenters change mid-stream, to include their gender as a variable in the analysis.

We do have gender-discrimination laws in this country, so I won’t make any comments regarding hiring.

Suddenly, lab animals are not just research tools in a cage, but creatures with the ability to sense (via smell) the presence of the male of many species—that mammalian half that is responsible for much of the aggression in the world—and NOT feel their pain, or your pain.

One cannot help but wonder how many potentially effective pain-relieving drugs have been tossed aside after the lack of an impressive reduction in facial grimacing compared to placebo—all because a male was in the room.

And that girlfriend of yours with whom you had lunch today, who never seems to get headaches: well, maybe that boyfriend of hers stresses her out. What a choice for some: a man, or an Advil.

(photo from Nature.com)

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