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Placebo and Nocebo Responses, Cortisol, and Circulating Beta-Endorphin

From the Departments of Orthopedic Surgery (O.J.) and Clinical Chemistry (J.B.), The University Hospital of North Norway, and the Department of Psychology (M.A.F.), University of Tromsø, Norway

Address all communications to: Magne Arve Flaten, Professor Dr. Psychol., Department of Psychology, SV-Fak., University of Tromsø, N-9037 Tromsø, Norway. Telephone: +47-77644344. Fax: +47-77645291. Email: magnef{at}psyk.uit.no

OBJECTIVE: The experiment tested whether the placebo and nocebo responses could be mediated via modulation of stress.

METHODS: Ischemic pain was induced in healthy volunteers (N = 59). When pain reached "7" on a 10-point scale, two groups of subjects received information that a pain relieving (the Placebo group) or a pain increasing (the Nocebo group) substance was injected. All injections contained physiological saline. A third group received no information and no injection (the Natural History group). Pain ratings and blood samples for analysis of cortisol and beta-endorphin were obtained every 5 minutes after pain equal to seven until the experiment was terminated.

RESULTS: Pain increased in all groups, but there were significantly lower pain ratings in the Placebo group at 15 minutes after the injection, compared with the other two groups. Cortisol increased in all groups, but mostly so in the Nocebo group. Circulating beta-endorphin increased in all groups. Pain-ratings were not correlated with beta-endorphins or cortisol.

CONCLUSIONS: A placebo response, ie, a reduced pain level, was seen in the Placebo group at 15 minutes after the injection. The placebo response was not related to stress or to beta-endorphin. Expectation of a pain increase in the Nocebo group led to an increase in cortisol, but the expectation of pain increase and the resultant cortisol increase had no effect on pain.

Key Words: Placebo analgesia, • nocebo, • ischemic pain, • stress, • cortisol, • beta-endorphin.

Abbreviations: ACTH = adrenocorticotropic hormone;; VAS = visual analog scale.

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