Sex differences in pain perception.
BACKGROUND
A number of studies have demonstrated a higher prevalence of chronic pain states and greater pain sensitivity among women compared with men. Pain sensitivity is thought to be mediated by sociocultural, psychological, and biological factors.


OBJECTIVE
This article reviews laboratory studies that provide evidence of sex differences in pain sensitivity and the response to analgesic drugs in animals and humans. The biological basis of such differences is emphasized.


METHODS
The literature from this relatively new field was surveyed, and studies that clearly illustrate the differences in pain mechanisms between the sexes are presented. Using the search terms sex, gender, and pain, a review was conducted of English-language literature published on MEDLINE between January 1980 and August 2004.


RESULTS
Although differences in pain sensitivity between women and men are partly attributable to social conditioning and to psychosocial factors, many laboratory studies of humans have described sex differences in sensitivity to noxious stimuli, suggesting that biological mechanisms underlie such differences. In addition, sex hormones influence pain sensitivity; pain threshold and pain tolerance in women vary with the stage of the menstrual cycle. Imaging studies of the brain have shown differences between men and women in the spatial pattern and intensity of response to acute pain. Among rodents, females are more sensitive than males to noxious stimuli and have lower levels of stress-induced analgesia. Male rodents generally have stronger analgesic response to mu-opioid receptor agonists than females. Research on transgenic mice suggests that normal males have a higher level of activity in the endogenous analgesic system compared with normal females, and a human study has found that mu-receptors in the healthy female brain are activated differently from those in the healthy male brain. The response to kappa-opioids, which is mediated by the melanocortin-1 receptor gene in both mice and humans, is also different for each sex.


CONCLUSIONS
Continued research at the genetic and receptor levels may support the need to develop gender-specific drug therapies.
Wiesenfeld-Hallin
Zsuzsanna
Z
Division of Clinical Neurophysiology, Karolinska Institutet, Stockholm, Sweden. Zsuzsanna.Wiesenfeld-Hallin@labmed.ki.se
D000700:Analgesics / Q000627:therapeutic use; D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy; D017288:Pain Threshold; D051381:Rats; D011957:Receptors, Opioid / Q000235:genetics; D012737:Sex Factors; D016896:Treatment Outcome
D000700:Analgesics; D011957:Receptors, Opioid