Men Trigger Stress in Mice
Of course I tweeted Hiring opportunities for #StemWomen when I saw the headlines. Jokes ensued. Could the gender of the researcher really have a noticeable effect on experimental outcomes with animals? This was a #journalclub worthy post, so here goes.
Don’t Stress Me Bro: Experimenters from a Montreal-based lab noticed anecdotally, that pain response in mice was less in human presence. Blunting of pain happens not when one has warm and fuzzy feelings, it turns out, but under stress. So an experiment was set up to measure pain response using a highly sensitive measure known as “mouse grimace scale”. Mice were anesthetized and injected in the leg with some yeast cell wall extract (zymosan) known to cause inflammatory pain. Their expressions were recorded by video and scored by a “blinded” observer, either in an empty room, or in the presence of a male or female lab person sitting quietly half a meter away. The grimace response was lower when a male was in the room. It didn’t matter if a female was present or not. Both male and female mice showed statistically significant response to guys, but the effect was larger in female mice!
Bros and BO: Rodents have a keen sense of smell, so the researchers tested if a T-shirt worn overnight by a male and place 0.5 m away would have the same effect. Yep, male BO was stressful, but female smells were ignored (oddly, the female shirt also cancelled out the effect of the male shirt. Why?). Males produce androgens and these are conserved in other animals. Pure samples of these chemicals had the same effect. Male cats and dogs had the same effect. So the researchers were on to something real.
Stress induced analgesia is an evolutionary adaptation thought to protect us in times of fight or flight. In the figure shown, panel a shows a rise in rodent stress hormone (corticosterone) levels by the mere presence of males, or their T-shirts. The stress response was similar to other unpleasant experiences such as being confined in a closed space or forced to swim! Actually, the animals were sh** scared (to be more scientific, they deposited more fecal boli; panel b). They became hot and bothered, as seen by the rise in body temperature (panel c).
What convinced me were the data in panel d. When triggered, pain-sensing neurons are known to produce a protein known as Fos. As you can see, Fos production after zymosan injection was significantly lowered by male presence. The rest of the paper showed that the effect could be blocked using drugs that reversed known opioid and non-opioid pain pathways. The study also examined other behavioral indicators of pain and stress and confirmed these findings.
Cause for Paws Pause: I can see that this gender-specific effect would add noise to data, but is it large enough to skew the overall conclusion? It is impressive that the effect could be mimicked by androgens, but they were used at very high, non-natural concentrations. Also, chemical effects ought to show a “dose response” and these were found to be weak. Still, I found the results in the attached figure to be convincing; how about you? Also, it gave me an excuse to post the cute mouse image.
REF: R.E. Sorge et al., “Olfactory exposure to males, including men, causes stress and related analgesia in rodents,” Nature Methods, doi:10.1038/nmeth.2935, 2014. http://goo.gl/9qpNh9