Table A1.
Characteristics of the experimental placebo–nocebo studies included in this paper.
| Paper ID | Sample Size (M, F, Not Analysed) * |
Population Type | Pain Type/Pain Induction | Investigated Outcome | Outcome Measure | Level of Significance |
|---|---|---|---|---|---|---|
| Amanzio and Benedetti, 1999 [20] | 229 (132, 97) | Healthy subjects | Experimental ischemic pain | Behavioral (Pharmacological) | Pain tolerance (min) | p < 0.05 |
| Amanzio et al., 2001 [21] | 364 (278 patients; 86 healthy controls) |
Patients (thoracic surgery) and healthy controls | Postoperative pain; experimental ischemic arm pain | Behavioral (Pharmacological) | NRS (0–10) | p < 0.05 |
| Benedetti et al., 1995 [40] | 93 (52, 41) | Patients (thoracotomy for lung surgery) | Post-surgery pain | Behavioral (Pharmacological) | NRS (0–10) | p < 0.02 |
| Benedetti et al., 1996 [39] | 340 (154, 186) | Healthy subjects | Experimental ischemic pain | Behavioral (Pharmacological) |
NRS (0–10) | p < 0.05 |
| Benedetti et al., 1997 [38] | 180 (119, 61) | Patients (video-assisted thoracoscopy) | Post-surgery pain | Behavioral (Pharmacological) | NRS (0–10) | p < 0.05 |
| Benedetti et al., 2006 [42] | 49 (23, 26) | Healthy subjects | Experimental ischemic pain | Behavioral (Pharmacological) | NRS (0–10) | p < 0.05 |
| Benedetti et al., 2006 [86] | 44 (28 patients (11, 17), 16 controls) | Patients (Alzheimer’s disease) and healthy subjects | Burning pain after venipuncture | Electrophysiological (EEG) | NRS (0–10) | p < 0.05 |
| Benedetti et al., 2010 [41] | 40 (20, 20) | Healthy subjects | Experimental ischemic pain | Behavioral (Pharmacological) | Tolerance time | p < 0.05 |
| Benedetti et al., 2011 [36] | 82 (41, 41) | Healthy subjects | Experimental ischemic pain | Behavioral (Pharmacological) | Tolerance time | 95%CI |
| Benedetti et al., 2014 [54] | 74 (30, 44) | Healthy subjects | Hypobaric hypoxia headache | Behavioral (Pharmacological) | NRS (0–10) | 95%CI |
| Benedetti et al., 2022 [37] | 149 (82, 67) | Healthy subjects | Experimental ischemic pain | Behavioral (Pharmacological) | 0–10 rating scale | p < 0.05 |
| Bingel et al. 2011 [85] | 22 (15, 7) | Healthy subjects | Heat pain | Neuroimaging (fMRI) | VAS (0–100) | p < 0.05 |
| Bingel et al., 2022 [100] | 22 (15, 7) | Healthy subjects | Heat pain | Neuroimaging; functional connectivity (fMRI) |
VAS (0–100) | p < 0.05 |
| Bush et al., 2021 [95] | 37 (12, 25) | Healthy subjects | Heat pain | Neuroimaging; functional connectivity (fMRI) |
VAS (0–100) | p < 0.05 |
| Camerone et al., 2021 [16] | 166 (78, 88, 9) | Healthy subjects | Electrical stimuli | Behavioral | NRS (0–10) | p < 0.05 |
| Camerone et al., 2021 [17] | 77 (24, 24, 29) | Healthy subjects | Cold pressor test (CPT) | Behavioral | Numerical Pain Intensity (0–100) | p < 0.05 |
| Camerone et al., 2022 [18] | 51 (24, 27, 10) | Healthy subjects | Cold pressor test (CPT) | Behavioral | NRS (0–10) | p < 0.05 |
| Carlino et al., 2015 [73] | 34 (20, 14) | Healthy subjects | Laser stimulation | Electrophysiology (EEG) | NRS (0–10) | p < 0.05 |
| Carlino et al., 2016 [26] | 80 (34, 46) | Healthy subjects | Electrical stimuli | Behavioral | NRS (0–10) | p < 0.05 |
| Colloca et al., 2006 [24] | 30 (5, 25) | Healthy subjects | Electrical stimuli | Behavioral | NRS (0–10) | p < 0.05 |
| Colloca et al., 2008 [21] | 116 (0, 116) | Healthy subjects | Electrical stimuli | Behavioral | NRS (0–10) | p < 0.05 |
| Colloca et al., 2010 [25] | 46 (16, 30) | Healthy subjects | Electrical stimuli | Behavioral | VAS (0–10 | p < 0.05 |
| Colloca et al., 2016 [50] | 109 (55, 54, 1) | Healthy subjects | Electrical stimuli | Behavioral | VAS (0–10) | p < 0.05 |
| Colloca et al., 2019 [105] | 160 (58, 102) | Healthy subjects | Electrical and heat stimuli | DNA genotyping; epistasis | VAS (0–10) | p < 0.001 |
| Colloca et al., 2020 [121] | 763 (363 patients (85, 278); 400 healthy controls (162; 238) | Patients (chronic orofacial pain) and healthy subjects | Heat stimuli | Behavioral | VAS | p < 0.05 |
| Disley et al., 2021 [30] | 104 (10, 65, 29) | Healthy subjects | Cold pressor test (CPT) | Behavioral | VAS (0–100) | p = 0.05 |
| Eippert et al., 2009 [34] | 48 (48, -, 8) | Healthy subjects | Heat pain | Neuroimaging (fMRI) | VAS (0–100) | p ≤ 0.05 |
| Eippert et al., 2009 [92] | 15 (15, 0) | Healthy subjects | Heat pain | Neuroimaging (fMRI) | VAS (0–100) | p < 0.05 |
| Ellerbrock et al., 2015 [35] | 40 (20, 20, 1) | Healthy subjects | Heat pain | Neuroimaging; functional connectivity (fMRI) | VAS (0–100) | p < 0.05 |
| Fuentes et al., 2014 [164] | 117 | Patients (chronic low back pain) | - | Behavioral | NRS (0–10) | p < 0.05 |
| Hashmi et al., 2014 [91] | 42 | Patients (chronic knee osteoarthritis) | Heat pain | Neuroimaging (fMRI) | Gracely Sensory Scale (0–20) | p < 0.05 |
| Jarcho et al., 2016 [46] | 15 (0, 15) | Healthy subjects | Heat pain | Neuroimaging (PET; fMRI) | VAS (0–100) | p < 0.005 |
| Kaptchuk et al., 2008 [111] | 262 (63, 199) | Patients (irritable bowel syndrome) | - | Behavioral | Global improvement scale (range 1–7); adequate relief of symptoms; symptom severity | p < 0.01 |
| Kelley et al., 2009 [165] | 189 | Patients (irritable bowel syndrome) | - | Behavioral | Combined outcome (IBS Symptom Severity Scale; IBS Quality of Like Scale; IBS Global Improvement Scale; IBS Adequate Relief) | p < 0.05 |
| Kessner et al., 2013 [51] | 80 (80, 0) | Healthy subjects | Heat pain | Behavioral (Pharmacological) |
Visual Analogue Scale (0–100) | p < 0.05 |
| Klinger et al., 2017 [112] | 48 (12, 36) | Patients (chronic back pain) | Electrical stimuli | Behavioral | NRS (0–10) | 95% CI |
| Kong et al., 2006 [57] | 24 (13, 11) | Healthy subjects | Heat pain | Neuroimaging (fMRI) | 0–20 Sensory Box Scale |
p < 0.0001 for ROI p = 0.05 |
| Kong et al., 2008 [71] | 20 (5, 8, 7) | Healthy subjects | Heat pain | Neuroimaging (fMRI) | Gracely Sensory and Affective Scales | p < 0.05 |
| Koyama et al., 2005 [70] | 10 (8, 2) | Healthy subjects | Heat pain | Neuroimaging (fMRI) | VAS | p < 0.01 |
| Krummenacher et al., 2010 [87] | 40 (40, 0) | Healthy subjects | Heat pain | rTMS | VAS (0–10) | p ≤ 0.05 |
| Kube et al., 2020 [29] | 117 (48, 53, 16) | Healthy subjects | Heat pain | Behavioral | Pain tolerance | p < 0.05 |
| Lieberman et al., 2004 [58] | 52 (29 active drug; 23 placebo condition) | Patients (irritable bowel syndrome) | - | Neuroimaging (PET) | Symptom diary (4 weeks) | p < 0.005 |
| Malfiet et al., 2019 [79] | 83 | Patients (chronic neck pain) | - | Behavioral | VAS (0–100) | p = 0.05 |
| Martins et al., 2022 [125] | 56 | Patients (chronic knee osteoarthritis) | - | Neuroimaging; functional connectivity (fMRI) | VAS (0–10) | p < 0.05 |
| Morton et al., 2010 [74] | 67 (21, 35, 11) | Healthy subjects | Laser stimulation | Electrophysiological (EEG) | 0–10 scale | p = 0.05 |
| Müller et al., 2016 [118] | 50 (27, 32, 1) | Patients (chronic pain) | Pressure-pain stimuli | Behavioral | VAS (0–100) | p < 0.05 |
| Olson et al., 2021 [113] | 280 (65, 215) | Patients (chronic orofacial pain) | Heat pain | Behavioral | VAS (0–100) | p < 0.05 |
| Peciña et al., 2015 [106] | 50 (21, 29) | Healthy subjects | 5% hypertonic saline | DNA genotyping; Neuroimaging (PET) | VAS (0–100) | p < 0.05 |
| Petrovic et al., 2002 [60] | 9 | Healthy subjects | Heat stimuli | Neuroimaging (PET) | VAS (0–100) | p = 0.005 |
| Petrovic et al., 2010 [59] | 24 (9, 15) | Healthy subjects | Heat stimuli | Neuroimaging (PET; fMRI) | VAS (0–100) | p < 0.05 |
| Piedimonte et al., 2017 [23] | 34(16, 18, -) | Healthy subject | Electrical stimuli | Electrophysiological (EEG) | NRS (0–10) | p < 0.05 |
| Ploghaus et al., 1999 [67] | 12 (7, 5) | Healthy subjects | Heat stimuli | Neuroimaging (fMRI) | VAS (0–10) | p < 0.05 |
| Pollo et al., 2001 [81] | 38 | Patients (thoracotomized patients) | - | Behavioral | NRS (0–10) | p < 0.01 |
| Porro et al., 2002 [69] | 30 (10, 16, 4) | Healthy subjects | Acid solution injection | Neuroimaging (fMRI) | 0–100 scale rating | p < 0.05 |
| Price et al., 1999 [162] | 40 (16, 24) | Healthy subjects | Heat pain | Behavioral | VAS (0–10) | p < 0.05 |
| Price et al., 2007 [61] | 9 | Patients (irritable bowel syndrome) | Barostat balloon distension—pressure stimuli | Neuroimaging (fMRI) | 100-unit rating scale | p < 0.05 |
| Prossin et al., 2022 [55] | 37 (12, 25) | Healthy subjects | Hypertonic saline injection | Neuroimaging (PET, MRI) | VAS (0–100) | p < 0.05 |
| Rief et al., 2012 [168] | 144 (50, 904) | Healthy participants | Heat pain | Behavioral | Pain threshold change in °C | p < 0.05 |
| Ruscheweyh et al., 2014 [98] | 60 (30 patients, 30 controls) | Patients (cerebellum infarction) and healthy subjects | Heat; pressure; pinprick pain | Behavioral | NRS (0–10) | p < 0.05 |
| Sawamoto et al., 2000 [83] | 10 (10, 0) | Healthy subjects | Laser thermal stimulation | Neuroimaging (fMRI) | 0–100 scale | p < 0.05 |
| Schmid et al., 2015 [84] | 44 (22, 22) | Healthy subjects | Rectal distension | Neuroimaging (fMRI) | VAS (0–100) | p < 0.05 |
| Schwartz et al., 2022 [161] | 44 (18, 26) | Patients (chronic low back pain) | - | Behavioral | NRS (0–10) | p < 0.05 |
| Scott et al., 2007 [49] | 48 (30 Study1; 16 Study2; 18 Male controls) | Healthy subjects | 5% hypertonic saline injection | Neuroimaging (Study1—PET, fMRI Study2—fMRI) |
VAS (0–100) | p < 0.05 |
| Scott et al., 2008 [43] | 20 (9, 11); 18 (18, 0) | Healthy subjects | Sustained muscle pain challenge | Neuroimaging (PET, MRI) | VAS (0–100) |
p < 0.0001 for ROI p = 0.05 |
| Skyt et al., 2018 [47] | 19 (10, 9) | Patients (neuropathic pain) | Pinprick-evoked pain; wind-up-like pain | Behavioral | VAS (0–10; 0–100) | p < 0.05 |
| Tétreault et al., 2016 [89] | 98 (17 Study1; 39 Study2; 42 Study3) | Patients (chronic knee osteoarthritis pain) | - | Neuroimaging (fMRI) | VAS (0–10); Western Ontario and McMaster Universities Osteoarthritis Index | p < 0.05 |
| Tinnermann et al., 2017 [99] | 57 (27, 22, 8) | Healthy subjects | Heat stimuli | Neuroimaging (fMRI) | VAS (0–100) | p < 0.05 |
| Tu et al., 2021 [88] | 81 (44, 37) | Healthy subjects | Heat stimuli | Neuroimaging (fMRI); tDCS | Gracely Sensory Scale (0–20) | p < 0.05 |
| Vachon-Presseau et al., 2018 [90] | 129 (43 placebo group, 20 controls, 66 excluded) | Patients (chronic back pain) | Back pain intensity | Neuroimaging (MRI, fMRI) | VAS (0–10) | p < 0.05 |
| Vachon-Presseau et al., 2022 [144] | 181 (94 randomized to 3 arms, 87 excluded) | Patients (chronic low back pain) | Back pain intensity | Neuroimaging (fMRI) | Likert Scale (twice a day) | p < 0.05 |
| Van der Meulen et al., 2017 [72] | 30 (13, 17) | Healthy subjects | Heat stimuli | Neuroimaging (fMRI) | VAS (0–100) | p < 0.05 |
| Vase et al., 2003 [82] | 13 | Patients (irritable bowel syndrome) | Evoked rectal distension; heat pain | Behavioral | VAS (0–10) | p < 0.05 |
| Vase et al., 2005 [110] | 26 (0, 26) | Patients (irritable bowel syndrome) | Rectal distension | Behavioral (Pharmacological) | VAS (0–10) | p < 0.05 |
| Vecchio et al., 2021 [77] | 63 (31, 32) | Healthy subjects | Electrical stimuli | Electrophysiological (EEG) | 7 point Likert scale | p = 0.05 |
| Wager et al., 2004 [64] | 47 | Healthy subjects | Shock pain; heat pain | Neuroimaging (fMRI) | 10 point scale | p < 0.05 |
| Wager et al., 2007 [65] | 15 (15, 0) | Healthy subjects | Heat stimuli | Neuroimaging (PET) | VAS (0–10) | p < 0.05 |
| Wager et al., 2011 [63] | 47 | Healthy subjects | Shock pain; heat pain | Neuroimaging (fMRI) | 10 point scale | p < 0.001 |
| Wanigasekera et al., 2018 [96] | 16 | Patients (Post-traumatic neuropathic pain) | - | Neuroimaging (MRI) | NRS (0–10) | p = 0.05 |
| Weimer et al., 2019 [108] | 39 (25 monozygotic; 14 dizygotic twin pairs) | Healthy subjects | Heat pain | Behavioral | NRS (0–10) | p < 0.05 |
| Wrobel et al., 2014 [48] | 50 (28, 32, 12) | Healthy subjects | Heat pain | Neuroimaging (fMRI); Pharmacological | VAS (0–100) | p < 0.05 |
* If not differently specified.