The magnitude of nocebo effects in pain: A meta-analysis

doi:10.1016/j.pain.2014.04.016

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Pain. Author manuscript; available in PMC 2014 Dec 1.

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Pain. 2014 Aug; 155(8): 1426–1434.

Published online 2014 Apr 26. doi: 10.1016/j.pain.2014.04.016

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Table 3

Induction of nocebo effects by verbal suggestions alone, verbal suggestions and conditioning or social observation.

Study	Pain measure	Time of pain measurement	Cohen’s d lowest (CI 95%^{^*2})	Cohen’s d highest (CI 95%^{^*2})	Hedges’ g ^{^3} lowest (CI 95%^{^2})	Hedges’ g ^{^3} highest (CI 95%^{^2})
*Verbal suggestions alone*

Benedetti et al. (1997)	NRS	Before the injection and after 30 min	2.10 (1.29-2.91)	2.10 (1.29-2.91)	2.05 (1.26-2.85)	2.05 (1.26-2.85)
Benedetti et al. (2003)	Tolerance^{^*1}	From last squeeze to unbearable pain	1.12 (0.29-1.95)	1.12 (0.29-1.95)	1.09 (0.28-1.89)	1.09 (0.28-1.89)
Colloca et al. (2008) ^{^*4}	NRS	After each stimulation	0.62 (−0.35-1.60)	0.62 (−0.35-1.60)	0.59 (−0.33-1.50)	0.59 (−0.33-1.51)
Johansen et al. (2003)	VAS	5 and 10 min after pain had reached 7 on a VAS	−0.45 (−1.13-0.24)	0.59 (−0.18-1.36)	−0.43 (−1.1-0.23)	0.58 (−0.17-1.32)
Vase et al. (2003)	M-VAS	After each stimulation	−0.04 (−0.83-0.76)	0.48 (−0.26-1.23)	−0.03 (−0.78-0.71)	0.45 (−0.25-1.15)
Vögtle et al. (2013) ^{^*5}	NRS	After each stimulation		0.60 (0.05-1.14)		0.59 (0.05-.113)

*Average d and g*			0.66 (−0.26-1.59)	0.90 (0.42-1.38)	0.64 (−0.25-1.53)	0.87 (0.40-1.34)

*Verbal suggestions and conditioning*

Benedetti et al. (2006)	NRS	Every minute for 10 min	1.40 (0.53-2.28)	4.19 (2.79-5.59)	1.35 (0.51-2.20)	4.05 (2.70-5.41)
Colloca et al. (2008) ^{^*4}	NRS	After each stimulation	1.13 (0.61-1.64)	1.13 (0.61-1.64)	1.06 (0.57-1.55)	1.06 (0.57-1.55)
Colloca et al. (2010)	VAS	After each trial	0.53 (0.20-0.85)	0.82 (0.48-1.17)	0.51 (0.20-0.82)	0.79 (0.46-1.13)
Elsenbruch et al. (2012)	VAS	After each stimulation	0.11 (−0.59-0.80)	0.23 (−0.47-0.92)	0.11 (−0.57-0.78)	0.22 (−0.46-0.90)
Kong et al. (2008)	VAS	After each stimulation	1.03 (0.45-1.61)	1.03 (0.45-1.61)	0.96 (0.42-1.50)	0.96 (0.42-1.50)

*Average d and g*			0.80 (0.41-1.20)	1.22 (0.55-1.90)	0.76 (0.39-1.14)	1.17 (0.52-1.81)

*Social observation*

Vögtle et al. (2013) ^{^*5}	NRS	After each stimulation	0.36 (−0.19-0.90)	0.36 (−0.19-0.90)	0.35 (−0.18-0.89)	0.35 (−0.18-0.89)

TOTAL d and g			0.65 (0.35-0.95)	0.79 (0.47-1.10)	0.63 (0.34-0.92)	0.77 (0.46-1.07)

^*1Pain was measured via tolerance and thus the sign of the effect sizes was changed.

^*2CI = confidence intervals.

^*3Effect sizes were weighted according to the number of subjects in each study (Hedges’ g) [30,31].

^*4Total d and g vary from the overall magnitude of nocebo effects (Table 2) as both verbal suggestions alone and verbal suggestions and conditioning are measured in Colloca et al. [21] and therefore the study is represented in both categories.

^*5In Vögtle et al. [65], the lowest effect size is induced by means of social observation and thus the effect size is only represented once (i.e., in the category of social observation).