Personality traits have been shown to interact with environmental cues to modulate biological responses including treatment responses, and potentially having a role in the formation of placebo effects. Here we used the Reinforcement Sensitivity Theory Personality Questionnaire (RST-PQ) to identify personality traits that predict placebo analgesic responding. Cardiac inter-beat (ReR) time series and electroencephalographic (EEG) band oscillations were recorded from healthy women in a cold-pain (Pain) and placebo analgesia (PA) condition. The measures of Hypnotizability, and self-reported ratings of Hypnotic Depth, Motivation, Pain Expectation, Involuntariness in PA responding, Pain and Distress intensity were obtained. Separate principal components factor analyses with varimax rotation were performed on summarized heart rate variability (HRV) measures of time, frequency, nonlinear Complexity, and EEG-band activity. Both analyses yielded a similar three-factor solution including Frequency HRV (factor-1), Complexity HRV dynamics (factor-2), and time HRV & EEG-delta activity (factor-3). Reward Interest sub-trait of the Behavioral Approach System (BAS-RI), Pain Expectation, Involuntariness in PA responding, and Hypnotic Depth were positively associated, whereas negative changes in time-HRV & EEG-delta scores were associated with Pain Reduction. Multiple mediation analyses disclosed that BAS-RI, potentially served by the dopaminergic system, through Involuntariness in PA responding can alter placebo responding to laboratory pain. Our results also show that a linear compound of HR slowing and higher EEG delta activity during PA explains a substantial proportion of the variance in placebo analgesic responses. Future studies should examine the potential role that these individual difference measures may play in patient responsiveness to treatments for clinical pain.