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Last updated January 1, 2014

Pain and Gender: Is There A Difference?

Fibromyalgia Network, June 1998

An NIH conference on April 7-8 provided a variety of speakers who all attempted to answer the question, "Is there a difference in how men and women process pain?" "We know that men's and women's brains are different," joked one presenter, "because women have a large processing center for chocolate cravings while men have one for sex!"

On a scientific level, genetics expert Jeffrey Mogil, Ph.D., from the University of Illinois at Urbana-Champaign commented: "One thing that should be kept in mind, in addition to sex differences that are a result of hormonal status, is that males and females have different brains from the start." Specific brain findings by Dr. Mogil and others are given below, followed by sections of other data presented at this two-day conference held in Bethesda, MD.


Brain Matters
"At this point in time, we have absolutely no idea what genes are relevant to pain," says Mogil. By birth, the vast majority of decisions have already been made about the structure and function of your brain as well as other body systems. These decisions, including whether you would turn out to be a boy or a girl, were based on the genetic inputs from your parents. So, it should come as no surprise that researchers such as Dr. Mogil are trying to pin down which genes are involved in processing pain and to better identify the differences that exist between males and females.

Many complicated gender-specific differences in the pain system of rodents have been documented, but what remains unknown is the genetic basis for these findings. Mogil thinks he has found a section on chromosome 4 in male mice that could explain why most studies have shown that women have lower pain thresholds than men. This particular section of the gene controls part of the opioid system in male mice, but it has no effect in female mice. This opioid receptor is present in the brain, spinal cord and other neurons, and Mogil suspects that it is responsible for regulating baseline pain sensitivity.

David Borsook, M.D., Ph.D., at Massachusetts General Hospital in Boston, is attempting to look at differences in brain function of humans when a painful stimulus is applied to a person's body. The procedure is called functional magnetic resonance imaging (fMRI). Borsook has divided his healthy female subjects according to where they are in their menstrual cycle: the mid-folicular phase which is around day 7 and the mid-luteal phase which is around day 22. He has found that women in the first phase of their cycle (folicular) and men look the same on fMRI measurements. However, there are distinct pain processing differences cropping up in women who are in the second half of their menstrual cycle.

"We think that these data provide the beginnings for implications of pain processing in the brain as a result of the estrogen and progesterone phases," says Borsook. He added that his fMRI technique could provide an objective way to measure responses to pain medications and, perhaps, pinpoint the brain processing centers that may be functioning differently between men and women.


Serotonin and Hormonal Variability
Studies show that FMS/CFS is more prevalent in women. Could this be due to the effects of estrogen, progesterone and testosterone on the pain system? Karen Berkley, Ph.D., of Florida State University in Tallahassee, says: "There are huge differences between males and females in serotonin within the spinal column." Serotonin is the chemical that is supposed to help "fight" the impact of the pain signals reaching the spinal cord. In fact, drugs such as antidepressants are often prescribed to people with FMS/CFS to help combat the pain because they are supposed to increase the effect of serotonin in the spinal cord and brain.

So what are the differences between males and females? The serotonin concentration in the spinal cord of lab animals is much higher in males than females. "This suggests," says Berkley, "that the serotonergic influences on the processing of information (including pain signals) would be greater in males than females."

Berkley says that there is a large shift in the way the central nervous system chemicals are produced (including serotonin) with response to the different stages of the female cycle. In addition, estrogen causes a cyclic growth of neurons. "We are beginning to see the variability in females that is not seen in males structurally," says Berkley.

Some research might indicate that women are just more likely than men to call a stimulus painful, but Berkley says that this is not the true picture, that there are many other factors involved. She conducted a study involving three sets of people: (1) healthy men, (2) healthy women, and (3) women with dysmenorrhea (painful menstruation). Berkley provided a pain stimulus to the skin of the arms and legs, as well as a deep tissue stimulus to the muscles of the abdomen. The healthy men and women responded the same to the skin tests. So on the surface, there seems to be no gender differences.

What about the abdomen? The pain threshold for women with dysmenorrhea was much lower (e.g., they were more sensitive to the pain) than for those women who were healthy. How did the men respond to the deep muscular stimulus to the abdomen compared to the women? "The men wouldn't let us near their abdomen!" says Berkley. Regardless of whether the examiners were male or female, the men in the study just dashed out of the room at the thought of touching their abdomen. The bottom line according to Berkley is that the presence of a disease condition (dysmenorrhea) made the women in the study more sensitive to pain and enhanced the cyclic nature of the pain all over the body (i.e., more pain when estrogen is low).


Chest Pain and Exercise
Women have been reported in studies to have a higher incidence of false positive stress tests for coronary artery disease compared to men, says David Sheps, M.D., of East Tennessee State University. What this means is that women who have already been documented to have coronary disease seemed more likely to return to their doctor when they experienced chest pain during daily living activities. When the males and females enrolled in Sheps' study were tested on a treadmill, which should precipitate chest pain indicative of coronary disease, few positive tests occurred in the women despite their chest pain complaints.

At first glance, it would be easy to say: "Well, women just seem more likely to complain than men." While it may appear this way, blood analyses of the body's natural pain killer, beta-endorphin, tell a different story. The beta-endorphin levels at rest were significantly lower for the women in the study.

In addition, Sheps' physiology colleague, David Sheffield, Ph.D., has been analyzing the blood levels of beta-endorphin in both men and women during the treadmill test. Ordinarily, the body pours out beta-endorphins during exercise and other stressful situations as a natural way to help combat the potential onslaught of pain. According to Dr. Sheffield, the amazing finding was that when women exercised, their beta-endorphin levels did not rise as high as their male counterparts-regardless of any diagnosis.

Are women just louder complainers, or is something else going on? Sheffield says that the pain fighting systems are physiologically different between men and women, and that this could explain why women sense more pain.


Sensory Differences
"There are sensory differences between the genders" says Jill Becker, Ph.D., of the University of Michigan at Ann Arbor. "Females tend to have greater taste preferences, greater odor detection, higher visual acuity and increased locomotor activity than do males. Estrogen tends to enhance these sex differences."

How this information applies to FMS/CFS was not addressed, but it is interesting to note that multiple chemical sensitivities and difficulty handling bright lights is a problem for many people with FMS/CFS. Although FMS is often thought of as a pain syndrome, the sensory detectors in patients might be more sensitive, not just for detecting pain, but also for sensing odors and other inputs to the nervous system.

"In addition to there being sex differences to naturally occurring behaviors, there are also sex differences to drug induced behaviors," says Becker. She points out that women are far more sensitive to stimulants such as amphetamines. So if you are a women with FMS/CFS and you need something to boost your energy level (who doesn't?), then you might want to think twice before consuming too many stimulants, such as coffee, tea, and other caffeine-containing beverages.


The Vulnerability Factor
Karen Berkley, Ph.D., points out that there is a female vulnerability factor that may increase a women 5 risk of activating the body's pain mechanisms. It's a variable that is easy to overlook, but it shouldn't be. "The vagina," says Berkley, "may provide an additional route in women for internal trauma, infection and invasion by pathological agents that puts them at greater risk for developing pain in multiple body regions."




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