Responses of Hypothalamic-Pituitary-Adrenal Axis to Cold Pressor Stimulation

Objective: Functional abnormalities of Hypothalamic-Pituitary-Adrenal (HPA) axis have been known implicated in chronic pain conditions (e.g., fibromyalgia). The purpose of this study was to establish an appropriate measure for the HPA axis responses by using cold pressor (CP) stimulation in humans. Methods: In CP trials, ten healthy males (mean age: 25.3+/-1.3 yrs) immersed their right hands for 2 minutes in 4 degree C cold water. Mock trials were also done without the cold water. Whole blood samples were collected 5 minutes before, during, and 5, 15, 30, 45, 60 minutes after CP and mock stimulation for measuring Corticotropin-Releasing-Factor (CRF), Adrenocorticotropic hormone (ACTH) and cortisol. These samples were drawn from an anterocubital vein of each subject. Whole blood was centrifuged for plasma separation, then frozen (-20 degree c) for later assay. Plasma CRF, ACTH and cortisol concentrations were determined using radioimmunoassay techniques. Blood pressure and heart rates were continuously monitored throughout the course of the CP and mock trials using an electric blood-pressure meter (Finapress BP monitor; Ohmeda, Louisville, USA). Results: Mean plasma ACTH levels significantly increased 5 minutes after cessation of CP stimulation and returned to the baseline in 60 minutes (p<0.01, One-way repeated measure ANOVA). Mean plasma cortisol levels also increased 30 minutes after cessation of CP stimulation (p<0.01), while no plasma CRF change was detectable (p=0.83). Blood pressure (p<0.01) and heart rate (p=0.01) significantly increased during CP stimulation. Meanwhile, no variables observed in this study showed a significant change in the mock trial. Conclusions: These results suggest that CP stimulation can be a good, uniform stimulator of HPA axis in healthy male subjects. This study was supported in part by Grant-In-Aid (No. 13672032) for Scientific Research from the Ministry of Education, Science and Culture, Japan.