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Elevated resting blood pressure (BP) and spontaneous baroreflex sensitivity (BRS) are associated with hypoalgesia to acute pain. These associations are significantly altered in chronic pain. We investigated whether degree of wind-up (marker for central sensitization) is similarly influenced by BP and BRS, and whether these associations are altered by chronic pain.BP and BRS (sequence method) were assessed in 30 healthy and 26 chronic back pain subjects who then completed a standardized thermal stimulation protocol to assess wind-up. This protocol was performed under placebo and α-2 adrenergic (ADRA2) blockade with yohimbine in counterbalanced order to test for the influence of ADRA2 mechanisms.1) In healthy controls, higher systolic BP was associated with lower wind-up (P < 0.05) but this was reversed in chronic pain subjects (P < 0.05); 2) higher BRS was associated with lower wind-up in healthy controls (P < 0.05) but not in the chronic pain group; 3) higher systolic BP was associated with lower BRS only in the chronic pain group (P < 0.05); and 4) ADRA2 receptor blockade did not significantly affect wind-up.These findings suggest that hypoalgesia associated with elevated resting BP and BRS in healthy individuals involves both diminished central sensitization (reflected in wind-up) and enhanced descending inhibition. The presence of chronic pain significantly alters the nature of these interactions. The reversal of normal interactions between overlapping systems modulating cardiovascular systems and pain in chronic pain patients may shift the healthy buffering of BP and heart rate toward instability and eventual higher BP and cardiovascular morbidity.