title: The relationship of allopregnanolone immunoreactivity and HPA-axis measures to experimental pain sensitivity: Evidence for ethnic differences.
abstract: In animal models, allopregnanolone (ALLO) negatively modulates the hypothalamic-pituitary-adrenal (HPA) axis and has been shown to exert analgesic effects. The purpose of this study was to assess the relationship between plasma ALLO immunoreactivity (ALLO-ir), HPA-axis measures, and pain sensitivity in humans. Forty-five African Americans (21 men, 24 women) and 39 non-Hispanic Whites (20 men, 19 women) were tested for pain sensitivity to tourniquet ischemia, thermal heat, and cold pressor tests. Plasma ALLO-ir, cortisol, and beta-endorphin concentrations were taken following an extended rest period. Lower concentrations of ALLO-ir were associated with increased pain tolerance to all three pain tests and increased pain threshold to the thermal heat pain task in the non-Hispanic Whites only (rs=-.35 to -.49, ps<.05). Also, only in the non-Hispanic Whites was cortisol associated with thermal heat tolerance (r=+.39, p<.05) and threshold (r=+.50, p<.01) and cold pressor tolerance (r=+.32, p<.05), and were beta-endorphin concentrations associated with cold pressor tolerance (r=+.33, p<.05). Mediational analyses revealed that higher cortisol levels mediated the relationship between lower ALLO-ir and increased thermal heat pain threshold in the non-Hispanic Whites only. These results suggest that lower ALLO-ir concentrations are associated with decreased pain sensitivity in humans, especially in non-Hispanic Whites, and that this relationship may be mediated by HPA-axis function.
authors.affiliation: Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Mechlin
authors.forename: A Leslie
authors.initials: AL
authors.lastname: Morrow
authors.forename: William
authors.initials: W
authors.lastname: Maixner
authors.forename: Susan S
authors.initials: SS
authors.lastname: Girdler
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D017288:Pain Threshold / Q000208:ethnology* / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000276:immunology*; D011280:Pregnanolone / Q000097:blood / Q000276:immunology*; D044465:White People
chemical_list: D011280:Pregnanolone