Sex differences in pain and hypothalamic-pituitary-adrenocortical responses to opioid blockade.
OBJECTIVE
Sex differences in pain sensitivity and stress reactivity have been well documented. Little is known about the role of the endogenous opioid system in these differences. This study was conducted to compare adrenocortical, pain sensitivity, and blood pressure responses to opioid blockade using naltrexone in men and women.


METHODS
Twenty-six participants completed 2 sessions during which placebo or 50 mg of naltrexone was administered, using a double-blind, counterbalanced design. Thermal pain threshold and heat tolerance were assessed. Participants also rated pain during a 90-second cold pressor test (CPT) and completed the McGill Pain Questionnaire (MPQ) after each pain challenge. Blood and saliva samples and cardiovascular and mood measures were obtained throughout the sessions.


RESULTS
Plasma cortisol, adrenocorticotropin, beta endorphin, prolactin, and salivary cortisol levels increased similarly in men and women after naltrexone administration compared with placebo. Women reported more pain during both pain procedures and had lower thermal pain tolerance. In response to naltrexone, women exhibited reduced blood pressure responses and reduced MPQ pain ratings after CPT. No effects of naltrexone on these measures were found in men.


CONCLUSIONS
Although men and women exhibited similar hormonal responses to opioid receptor blockade, women reported less pain and showed smaller blood pressure responses during CPT. Results suggest differential effects of the endogenous opioid system on pain perception and blood pressure in men and women.
al'Absi
Mustafa
M
Department of Behavioral Sciences, University of Minnesota School of Medicine, Duluth, Minnesota 55812, USA. malabsi@umn.edu
Wittmers
Lorentz E
LE
Ellestad
Deanna
D
Nordehn
Glenn
G
Kim
Suck Won
SW
Kirschbaum
Clemens
C
Grant
Jon E
JE
D000324:Adrenocorticotropic Hormone / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects* / Q000528:radiation effects; D004311:Double-Blind Method; D004723:Endorphins / Q000037:antagonists & inhibitors* / Q000502:physiology; D005260:Female; D006358:Hot Temperature; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis / Q000097:blood; D008297:Male; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010919:Placebos; D011388:Prolactin / Q000097:blood; D012463:Saliva / Q000737:chemistry; D012737:Sex Factors; D001615:beta-Endorphin / Q000097:blood
D004723:Endorphins; D009292:Narcotic Antagonists; D010919:Placebos; D009271:Naltrexone; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D006854:Hydrocortisone