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July 03, 2014 | By:  Luke De
Aa Aa Aa

Of Mice Pain and Man Treatment

The Relationship between Males and Pain.

BASED ON THE ARTICLE IN NATURE METHODS

Sorge, R. E., Martin, L. J., Isbester, K. a, Sotocinal, S. G., Rosen, S., Tuttle, A. H., … Mogil, J. S. (2014). Olfactory exposure to males, including men, causes stress and related analgesia in rodents.

I would have loved to have been the person that proposed this idea: Imagine a group of scientists eating lunch together. After a strange science joke, one hesitantly offers, “oh, I get it a talking sausage[a]. . . so talking about pain, I think that mice make fewer ouchie faces when there is a male in the room.”


And that is exactly why I love science. From a statement like that, foundations are shaken. What if the gender of a person running an experiment on pain mattered? What would happen if a single experiment was run by alternating scientists (male and female) on alternating days? Can a pain experiment done by a male be compared to a similar pain experiment done by a female.

This experiment started anecdotally from the something like the reference above. Mice make faces and somebody has been watching them very closely.

Mice grimace less in response to pain when there is a male in the room.

The basic experiment:

There are three basic parts to this experiment. The thing causing the pain, Zymosan A or Formalin injection. The measure of the pain, the mouse’s facial expression, specifically its grimace. The treatment, in this case the presence of a male.

The initial experiments were done with Zymosan A injections in the paw. This causes pain. The pain then can be measured by the grimace of the mouse. In this case, when there was a male (human) in the room there was less of a grimace.

Do you need the whole male?

Nope, it turns out you just need the smell of a male. When the experiment was repeated with a male’s t-shirt, the result was similar. Interestingly, the presence of a female t-shirt reversed the effect, and the effect of the male shirt gradually lessened over time. If the

male shirt was left in the room, the effect decreased over time. If, however, the male shirt was removed and reintroduced the next day, the effect was seen.

When bedding was used from different male animals, the result was similar, unless the males were castrated. This led the group to believe that the effect was the result of male pheromones.

So how does it work?

To figure this out, the scientists switched to formalin as the pain-causing-agent. The pain generated by formalin falls in to two phases, one following the other. Phase 1 isn’t affected by anti-inflammatories (e.g. Advil) but both phases are affected by opiates.1,2 Male-stench affected both phases.

Now, using the premise that male-stench was affecting a neurological pathway instead of just reducing inflammation, the group suspected SIA, stress-induced analgesia[b]. This is a decrease in the transmittance of pain as a result of stress, and of course male-stench-stressed[c] mice showed a rise in corticosterone.

Is it like drugs?

There are different forms of stress-induced analgesia. Some use the opiate pathways and some do not, and some use a combination.3 It turns out that the male-stench induced SIA is at least partially blocked when the opioid system is blocked.

Fancy wording.

The last paragraph of scientific articles is often what I like to call the grant appeal.[d] They generally go something like this: “and this may pave the way for a new treatment of (insert disease that has reached epidemiological proportions here).”

The authors made the following statement at the end of their article. “[this] may represent a confound of much existing animal research, extending even to non-behavioral studies in which tissues were obtained from live rodents euthanized by either male or female personnel.” What it means: “well, oh crap, we now have to look at who did any experiment involving pain, opioid systems, and stress.”

This article may pave the way for a new treatment of really, really poor experimental design being conducted by students (mostly mine) everywhere.

Sincerely,

Luke De

Edited by Krista Maxwell
Special Thanks to Teddy Leithead (Dingbat Student) for bringing this article to my attention.

[a] So there are two sausages in a frying pan. The first says “Is it getting hot in here?” The second says, “Holy crap, a talking sausage!”

[b] pain relief

[c] They also looked at progression of hypothermia, and increases in fecal boli.

[d] Cake just wrote a song about this. Federal Funding, I hear he is going to follow this with a song about Fecal boli (the last part is not true)

Copyedited by Krista Maxwell

Refrences

1. Hunskaar, S. & Hole, K. The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain 30, 103–114 (1987).

2. Tjolsen, A., Berge, O. G., Hunskaar, S., Rosland, J. H. & Hole, K. The formalin test: An evaluation of the method. Pain 51, 5–17 (1992).

3. Sorge, R. E. et al. Olfactory exposure to males, including men, causes stress and related analgesia in rodents. Nat. Methods (2014). doi:10.1038/nmeth.2935

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