Multilevel Pain Phenotyping (SIP2)

A full understanding of the mechanisms involved in chronic pain could make a significant difference in the quality of life of chronic pain patients, as well as healthcare costs and productivity. Previous clinical studies have found associations between pain conditions and levels of C-Reactive Protein (CRP), a general indicator of inflammation in the body. This study examined the relationship between underlying pain sensitivity and CRP and other inflammatory markers.

This study was a multi-level examination of the relationship between pain perception/sensitivity and exercise, weight, sleep, psychological stress, and inflammatory markers such as CRP. Twins were studied in order to see if there are genes that contribute to the association between pain sensitivity and CRP.

Two hundred (200) same-sex twin pairs, both male and female, took part in this study. Both members of each pair visited the University of Washington Medical Center together for a half-day of study activities. These included collection of blood samples, completion of pain and sensitivity tasks (hot pain, cold pain, pressure pain and vibration), and responses to questions about pain, mood, stress, and other pain-related factors.

We rely on self-reported information for many measures. For this study, we collected self-reported height and weight when the twins arrived, and then measured actual height and weight. This is helpful to determine how accurately people report their height and weight. The following graph shows the strong relationship between self-reported BMI and measured BMI for female twins and male twins, which means that our self-reported measures of height and weight are very close to actual height and weight.

Because this study recruited both identical and fraternal twins, we can see how the BMI for one twin correlates with the other. The correlation for identical males and identical females is fairly high, with 0.87 for males and 0.85 for females (1.0 would be perfect correlation). The correlation for fraternal females is moderately high at 0.51, and fairly low for fraternal males at 0.15. This shows that there is a strong genetic component to one’s BMI.


One of the tasks in this study involved placing the entire dominant arm into a bath of ice water. Participants were instructed to indicate when they first felt pain (threshold), rate their pain level, and then indicate when the pain was so great they wished to stop (tolerance), and rate their pain level. Participants rated their pain level on a scale from 0-100, with 100 being the worst pain ever.  The following graph shows the relationship between the tolerance pain level for twin A and twin B.


There is a moderately strong correlation between the pain rating for identical twins, with female twins having a stronger correlation (0.65) than male twins (0.56). Fraternal female twins have a fairly low correlation at 0.27, and fraternal male twins have no correlation at 0.00. Once again, this shows that there is a genetic component to the perceived amount of pain one feels when exposed to extreme cold temperature.

It is interesting to note that although there is a correlation between identical twins’ pain ratings when exposed to cold, this relationship goes away when exposed to hot pain. Another task that was completed by twins in this study involved having a thermode attached to the top of the arm or the top of the foot. This thermode gradually increased in temperature, and participants clicked a mouse to stop the machine at the point where they first felt pain, and then later at the point when the pain was so great they wished to stop. This test was done 6 times each for threshold and tolerance on both the arm and the foot. Participants rated their pain level on a scale from 0-100, with 100 being the worst pain ever.  The following graph shows the relationship between the average tolerance pain level for twin A and twin B.


While both identical male and female twins had a moderately strong correlation with cold pain, in the hot pain task only identical female twins still had a correlation, which was fairly low at 0.23. The correlation for identical males dropped to 0.08. Fraternal female twins also have a fairly low correlation at 0.16. The correlation for male twins was slightly higher than the cold pain task, but still almost non-existent at 0.03.

Published Research