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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&lt;.05). Also, only in the non-Hispanic Whites was cortisol associated with thermal heat tolerance (r=+.39, p&lt;.05) and threshold (r=+.50, p&lt;.01) and cold pressor tolerance (r=+.32, p&lt;.05), and were beta-endorphin concentrations associated with cold pressor tolerance (r=+.33, p&lt;.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.

The relationship of allopregnanolone immunoreactivity and HPA-axis measures to experimental pain sensitivity: Evidence for ethnic differences ☆