Stress Promotes Skin-Healing in Mice

Everyone has experienced the effects of stress: fidgeting, sweating, inability to focus, gain or loss of appetite, racing heartbeat, and so on. All of these things can happen to us when the adrenal system releases "stress hormones," a process that often disrupts many aspects of daily life. We don't like it. Our aversion to stress has sparked a cottage industry of self-help books, seminars, podcasts, videos, and various therapies that claim to teach us how to chill out and stay calm.


Although the "symptoms" of stress make us uncomfortable, there should be some benefit that has encouraged the body to keep doing this to us, generation after generation, right? The adrenal system is a complicated machine, and it seems unlikely that responding to stress by throwing our hormones out of kilter is just an arbitrary (and unkind) evolutionary dalliance. Although stress can be psychologically disturbing, the body does indeed mount these responses for a reason: to physiologically boost us in times of need. So in reality, the typical stress response is like nasty medicine that the body subjects us to for our own good.

For example, glucocorticoids (GCs) are steroidal "stress hormones" with anti-inflammatory properties. One reason that we think of stress as a negative phenomenon is that chronic elevation of GCs can exacerbate the severity of inflammatory disorders, ranging from cardiac disease and inflammatory bowel syndrome to skin conditions and wound recovery.

There is more and more evidence that short-term spikes in GCs can be beneficial, however--and a stressful situation is typically the stimulus for a GC boost from the adrenal system. In a study recently published in the Journal of Investigative Dermatology (Lin et al. 2014), a group of researchers led by Dr. Peter Elias asked the question of whether these GC boosts, although psychologically unpleasant for humans, may actually have observable health benefits. Dr. Elias and his group at the San Francisco VA Medical Center have done previous research demonstrating that extended exposure to endogenous steroids is harmful to a variety of organs--including the skin--and yet in this study they address the effects of short-term stress.

To assess the effects of acute yet brief stress on healing, the researchers tested whether 1) short-term stress would affect healing rates in mice, and 2) whether GCs appear to be the cause of differences in healing rates between the stressed and control groups. Irritating liquids applied to the mice's skin to induce abrasions, and healing rates were then quantified by measuring epidermal thickness, proliferation, and inflammatory cell density at the wound sites. The stress treatment used in this study was enclosure in a very confined space for 18 hours a day over four days after the skin was damaged. The researchers used both male and female hairless mice, presumably to avoid dealing with fur when applying the skin irritants.


Being a hairless lab mouse just seems like a stressful condition in general.


To summarize, these were the three types of experimental treatments:

  1. Mice with irritated ears that did not undergo the stress treatment
  2. Mice with irritated ears that did undergo the stress treatment
  3. Mice with irritated ears that underwent the stress treatment as well as being given mifepristone, a synthetic steroid that blocks GC activity.

It could be argued that the control group still had to undergo the stress of the skin irritation, but those mice did objectively experience much less distress than did the group that was put in close confinement chambers for days afterward.

The results of the experiment confirm that stress isn’t always bad: the stressed mice healed more quickly than those that did not undergo the stress treatments. In other words, being wounded and then stressed out yielded better outcomes that being wounded but then being left to recover in peace.

In addition, the mice that were given both the stress treatment and the GC-blocking hormone did not heal any faster than the unstressed mice. The mifepristone essentially canceled out the healing benefits of the stress treatment. These mice really were the losers in the experiment, it seems. This part is key, however, because it verifies that GCs released during the stress treatment were indeed the factors responsible for the faster healing responses.



(Click to embiggen)


So, why is this study news-worthy? First, the results validate that immune cells aren’t the only helpers during wound-healing—endogenous, anti-inflammatory steroids can provide significant curative benefits as well. Second, the study demonstrates that acute stress can actually be beneficial in some situations.

Our bodies often react in ways that seem inconvenient or even nonsensical in the context of modern life (did sweaty palms help any of us on dates as teenagers? Evolutionary fitness FAIL). Still, this doesn't mean that the body is completely betraying us--our ancestors couldn't swallow a few Advil to reduce swelling after a knock on the head, and a stress response that involves a spike in GCs was a useful way to achieve the same effect endogenously. Of course, the issue of chronic stress is still a whole different world of health problems, but the new study by Elias and colleagues shows that we shouldn't see stress as the enemy--we should just try not to let it become a constant in our lives.


To summarize this Lin et al. 2014 in meme form.
Lin TK, Man MQ, Santiago JL, Scharschmidt TC, Hupe M, Martin-Ezquerra G, Youm JK, Zhai Y, Trullas C, Feingold KR, & Elias PM (2014). Paradoxical Benefits of Psychological Stress in Inflammatory Dermatoses Models Are Glucocorticoid Mediated. The Journal of investigative dermatology PMID: 24991965
Image Sources

Stress Free Zone Sign
Hairless mouse

Dermatology slides: Lin et al. 2014

If you have no idea where the "Keep Calm" bit came from, improve your meme knowledge here.

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