In our April 2012 TMJ News Bites, we reported on a study by Chinese scientists suggesting that estrogen increases pain sensitivity in the jaw by stimulating a brain center (the hippocampus) to express receptors for acid, heat and other noxious stimuli. The experiment used female rats with inflamed jaws whose ovaries had been removed. When rates were given replacement estrogen hormones, they displayed behaviors indicating pain in response to normally mild pressure in comparison to females without ovaries that were not given replacement hormones.
Now comes a report out of Brazil, again using rats but with opposite results. Estrogen decreased inflammation (and thus the pain associated with inflammation) in rats in which one temporomandibular joint was injected with formalin to model TMJ disease.
The investigators noted that formalin injection results in a leaking of blood plasma into the joint space (swelling the tissues) and also induces the migration of particular immune cells, neutrophils, to the site, which is associated with tissue injury. They did a series of experiments with both male and female rats, either with ovaries or testes intact or removed. Sometimes the scientists added estrogen or testosterone to the animals whose sex organs had been removed, also sometimes adding chemicals that would block the action of the hormones. In the case of females with ovaries intact, they varied the time of their formalin injections to coincide with the times in the rats’ reproductive cycle when estrogen levels were either at the highest (just prior to ovulation) or lowest levels (equivalent to just before menstruation in women).
No matter how they sliced and diced the experimental procedures, the level of inflammation as measured by blood plasma leaking into the joint and the level of immune cells found there, was lower when estrogen levels were high. Thus, in intact females, if formalin was injected at the pre-ovulatory phase of the reproductive cycle (when estrogen is high) the anti-inflammatory effects were greater than when formalin was injected at the phase of the cycle when estrogen levels are lowest. Similarly, when female rats without ovaries were injected with replacement estrogen the anti-inflammatory effects were restored, compared to females without ovaries who did not receive replacement estrogen. Even injections of testosterone at somewhat higher doses than would be normally present, had anti-inflammatory effects in male rats whose testes had been removed. These restorative effects in both female and males without sex organs were blocked when the animals were injected with hormone-blocking compounds.
We know that the Chinese and Brazilian scientists were looking at different models of TM disease, different measures of pain, different behavioral indicators, and so on. Given these contradictory results we can best conclude that the jury on estrogen is still out (and also that it is not unusual for science to chart a contradictory course before arriving at a resolution of findings).
We would be interested in having your input on this issue. Do you notice any difference in the level of TMD pain and discomfort you experience depending on where you are in your menstrual cycle? (Click here to read the patient responses we received from this request.)
Source: Torres-Chávez, K.E., Sanfins, J.M., Clemente-Napimoga, J.T., Pelegrini-Da-Silva, A., Parada, C.A., Fischer, L. and Tambeli, C.H. (2012), Effect of gonadal steroid hormones on formalin-induced temporomandibular joint inflammation. European Journal of Pain, 16: 204–216.doi: 10.1016/ j.ejpain.2011.06.007