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The Journal of Neuroscience, May 15, 2003, 23(10):4315-4323
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Conscious Expectation and Unconscious Conditioning in Analgesic, Motor, and Hormonal Placebo/Nocebo Responses
Fabrizio Benedetti,1,2 Antonella Pollo,1,2 Leonardo Lopiano,1 Michele Lanotte,4 Sergio Vighetti,1 andInnocenzo Rainero1,3 1Department of Neuroscience, University of Turin Medical School, Turin, Italy 10125, 2Department of Clinical and Applied Physiology Program, University of Turin Medical School, Turin, Italy 10125, 3Department of Neurology III–Headache Center, University of Turin Medical School, Turin, Italy 10125, and 4Division of Neurosurgery, CTO Medical Center, Turin, Italy 10126
The placebo and nocebo effect is believed to be mediated by both cognitive and conditioning mechanisms, although little is known about their role in different circumstances. In this study, we first analyzed the effects of opposing verbal suggestions on experimental ischemic arm pain in healthy volunteers and on motor performance in Parkinsonian patients and found that verbally induced expectations of analgesia/hyperalgesia and motor improvement/worsening antagonized completely the effects of a conditioning procedure. We also measured the effects of opposing verbal suggestions on hormonal secretion and found that verbally induced expectations of increase/decrease of growth hormone (GH) and cortisol did not have any effect on the secretion of these hormones. However, if a preconditioning was performed with sumatriptan, a 5-HT1B/1D agonist that stimulates GH and inhibits cortisol secretion, a significant increase of GH and decrease of cortisol plasma concentrations were found after placebo administration, although opposite verbal suggestions were given. These findings indicate that verbally induced expectations have no effect on hormonal secretion, whereas they affect pain and motor performance. This suggests that placebo responses are mediated by conditioning when unconscious physiological functions such as hormonal secretion are involved, whereas they are mediated by expectation when conscious physiological processes such as pain and motor performance come into play, even though a conditioning procedure is performed.
Key words: expectation; conditioning; placebo; pain; Parkinson's disease; hormones
Received Dec. 2, 2002; revised Jan. 31, 2003; accepted Feb. 7, 2003.
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