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Randomized Controlled Trial
. 2024 Feb 1;165(2):440-449.
doi: 10.1097/j.pain.0000000000003035. Epub 2023 Sep 8.

Placebo analgesia and nocebo hyperalgesia in patients with Alzheimer disease and healthy participants

Susan Tomczak Matthiesen  1 , Mette Sieg  1 , Stephanie Skøtt Andersen  1 , Martina Amanzio  2 , Nanna Brix Finnerup  3   4 , Troels Staehelin Jensen  3 , Hanne Gottrup  4 , Lene Vase  1
Affiliations
Randomized Controlled Trial

Placebo analgesia and nocebo hyperalgesia in patients with Alzheimer disease and healthy participants

Susan Tomczak Matthiesen et al. Pain. .

Abstract

The role of placebo analgesia and nocebo hyperalgesia in patients with Alzheimer disease (AD) is largely unknown, with only few studies in the area. Therefore, this study aims to investigate to which extent placebo analgesia and nocebo hyperalgesia effects are present in patients experiencing mild-to-moderate AD. Twenty-one patients with AD (test population) and 26 healthy participants (HP; design validation) were exposed to thermal pain stimulation on 3 test days: Lidocaine condition (open/hidden lidocaine administration), capsaicin condition (open/hidden capsaicin administration), and natural history (no treatment), in a randomized, within-subject design. Open lidocaine and open capsaicin were accompanied by verbal suggestions for pain relief and pain increase, respectively. Expected pain and actual pain intensity were measured on a numerical rating scale (0-10). Placebo and nocebo effects were calculated as pain differences in open-hidden lidocaine and capsaicin, respectively, controlled for no treatment. Healthy participants obtained a placebo effect ( P = 0.01) and a trend for a nocebo effect ( P = 0.07). Patients with AD did not obtain a placebo effect ( P = 0.44) nor a significant nocebo effect ( P = 0.86). Healthy participants expected lower and higher pain with open vs hidden lidocaine and capsaicin, respectively ( P < 0.001). The same expectation effects were seen in patients with AD (open vs hidden lidocaine, P = 0.008; open vs hidden capsaicin, P < 0.001). With a well-controlled experimental setting, this study suggests that patients with AD may not experience placebo analgesia effects. Nocebo hyperalgesia effects in patients with AD needs further research. These findings may have implications for the conduction of clinical trials and the treatment of patients with AD in clinical practice.

Trial registration: ClinicalTrials.gov NCT03709238.

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References

    1. Amanzio M, Benedetti F, Vase L. A systematic review of adverse events in the placebo arm of donepezil trials: the role of cognitive impairment. Int Psychogeriatrics 2012;24:698–707.
    1. Amanzio M, Pollo A, Maggi G, Benedetti F. Response variability to analgesics: a role for non-specific activation of endogenous opioids. PAIN 2001;90:205–15.
    1. Aslaksen PM, Flaten MA. The roles of physiological and subjective stress in the effectiveness of a placebo on experimentally induced pain. Psychosom Med 2008;70:811–8.
    1. Benedetti F. Placebo Effects. Oxford, United Kingdom: Oxford University Press, 2014.
    1. Benedetti F, Arduino C, Costa S, Vighetti S, Tarenzi L, Rainero I, Asteggiano G. Loss of expectation-related mechanisms in Alzheimer's disease makes analgesic therapies less effective. PAIN 2006;121:133–44.

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