Responses of the hypothalamic-pituitary-adrenal axis and pain threshold changes in the orofacial region upon cold pressor stimulation in normal volunteers

Aim: This study focused on the relationship between the HPA axis function and the heat pain threshold in the orofacial region upon cold pressor (CP) stimulation. Methods: Ten healthy male individuals participated in this study. CP stimulation was applied to each participant, and their peripheral blood was collected 5 min before, during and 5, 15, 30, 45, 60 min after receiving CP. In addition, 5 of those 10 participants were selected at random and they experienced a mock CP trial on different days. The heat pain thresholds on the facial skin about 10 mm anterior to the right external auditory canal (trigeminal V2 region) in each subject were simultaneously recorded 5 min before and 5, 30, 60 min after CP stimulation. The blood pressure and heart rate were continuously monitored throughout the course of the CP and mock trials using an electric blood pressure meter. Results: Significant increases in the plasma concentration of cortisol, β-endorphin and ACTH were induced by CP stimulation, while no significant increases were observed under the mock trial conditions. The blood pressure and heart rate showed concomitant increases during CP stimulation. In addition, the heat pain threshold in the orofacial region significantly increased after receiving CP stimulation. These results suggest that CP stimulation activated the HPA axis thereby increasing the heat pain threshold in the orofacial region in healthy individuals. Conclusions: This observed pain threshold increase might be due to the activation of an endogenous opioid system, such as increase in the circulating β-endorphin levels.