Gender effects in placebo responses in experimental nausea

The placebo response (PR) is thought to be generated by two basic mechanisms, Pavlovian conditioning (PC) and manipulation of expectancies by suggestions (ES). Gender effects of the PR have rarely been dokumented and were studied in two experiments using a motion-sickness paradigm here. Experiment 1 (PC): 48 healthy male and female volunteers were investigated on three days 1 week apart using a standard rotations procedure (5×1min, eyes closed, 120 degrees/s). Subjects in the PC group received a salient oral stimulus (Cinnamon Listerine PocketPaks® breath strips, Pfizer, Morris Plains, NJ, USA) immediately prior to rotation, subjects of the control group received the stimulus 12h after the rotation on day 1 and 2; on day 3, all subjects received the stimulus prior to rotation. Experiment 2 (ES): 45 healthy male and female subjects were randomised to a placebogroup (PG), a nocebo group (NG), and a control group (CG); all were rotated once 5×1min only. All subjects received the same oral stimulus immediately prior to rotation; PG subjects were given the information, that a strong taste stimulus would improve nausea symptoms, NG subjects were suggested a worsening of symptoms by the stimulus, CG subjects did not receive additional information. In both experiments, rotation tolerance (RT) and symptom rating (SR) were determined as the main dependent measures. Experiment 1 showed a significant interaction group x gender (F=3.67, p=.034), according to which the conditioning occured predominantly in women. In Experiment 2, RT was significantly reduced in both PG and NG (F=4.06, p=.05), and men exhibited a significant reduction in RT (F=4.1, p=.049 and responded stronger to rotation and suggestions than women. SR was less effective in PC and ES. We conclude that PC and ES of nausea are both effective mechanisms of the PR, but PC is more effective in women, while ES of nausea shows a higher efficacy in men.

(Supported by DFG, EN 50/25 and KL 811//2)

Fig.1: Gender differences in nausea conditioning and suggestion: Rotation tolerance (RT) (in s, sum of 5 rotations of 60s each) in males (dotted) and females (solid line)