Abnormalities in pain sensitivity among individuals with autism spectrum disorder: Evidence from meta-analysis

doi:10.3724/SP.J.1041.2021.00613

Abstract

Abstract:

A meta-analysis was conducted to assess the abnormalities of pain sensitivity among individuals with autism spectrum disorder (ASD), which were characterized as pain threshold, pain-evoked physiological responses, and pain intensity ratings. This understanding has the potential to provide evidence-based guidelines for early diagnosis and intervention of ASD. Sixteen experimental studies were included in the meta-analysis, with a total sample size of N = 822. Pain thresholds were not significantly different between ASD and control groups, but this estimate was moderated by the variable of pain modality, such that individuals with ASD exhibited lower pressure pain thresholds than the controls. Pain-evoked physiological responses were significantly greater among individuals with ASD than the controls, but pain intensity ratings were comparable between ASD and control groups. Future studies should combine multi-modal painful stimulations and multi-dimensional measures to comprehensively investigate the pain sensitivity profiles for individuals with ASD and establish the link between their pain sensitivity and clinical core symptoms.

Key words: autism spectrum disorder, pain sensitivity, meta-analysis, pain threshold, pain-evoked physiological responses

ZHANG Wenyun, LI Xiaoyun, YAO Junjie, YE Qian, PENG Weiwei. (2021). Abnormalities in pain sensitivity among individuals with autism spectrum disorder: Evidence from meta-analysis. Acta Psychologica Sinica, 53(6), 613-628.

Figures/Tables 7

References 89

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Research	Sample size and age of ASD group	Sample size and age of control group	Pain modality	Pain location	Outcomes	Region	Results
Fan et al., 2014	n = 24 age：18.4 ± 2.8	n = 21 age：19.3 ± 3.4	pressure pain	left and right hands (proximal phalanx dorsally of index finger)	pain threshold	Asia	ASD low pain threshold, high pain sensitivity↑
Chen et al., 2017	n = 37 age：18.2 ± 5.2	n = 34 age：19.3 ± 4.6	pressure pain	left and right hands (proximal phalanx dorsally of index finger)	pain threshold	Asia	ASD low pain threshold, high pain sensitivity↑
Riquelme et al., 2016	n = 27 age：6.3 ± 3.2	n = 30 age：6.5 ± 3.4	pressure pain	Face dorsum of hand palm	pain threshold	Europe	ASD low pain threshold, high pain sensitivity↑
Chien et al., 2017	n = 31 age：20.5 ± 5.2	n = 22 age：21.4 ± 2.6	heat pain	leg (lateral)	pain intensity rating	Asia	no significant difference?
Failla et al., 2018	n = 15 age：27.5 ± 10.3	n = 16 age：30.1 ± 10.9	heat pain	leg (lateral)	pain threshold pain intensity rating	America	no significant difference?
Dubois et al., 2020	n = 19 age：31.5 ± 8.5	n = 19 age：31.6 ± 8.4	heat pain	forearm	pain intensity rating	Europe	no significant difference?
Cascio et al., 2008	n = 8 age：29.3 ± 10.5	n = 8 age：29.0 ± 9.7	cold pain heat pain	forearm palm	pain threshold	America	ASD low pain threshold, high pain sensitivity↑
Duerden et al., 2015	n = 20 age：14.6 ± 1.9	n = 55 age：15.7 ± 1.1	cold pain heat pain	forearm	pain threshold	America	no significant difference?
Bird et al., 2010	n = 18 age：34.6 ± 13.3	n = 18 age：35 ± 12.8	electrical pain	dorsum of hand	pain threshold	Europe	no significant difference?
Thaler et al., 2018	n = 16 age：25.5 ± 5.4	n = 16 age：24.5 ± 2.7	electrical pain	dorsum of hand	pain threshold pain intensity rating	Europe	no significant difference?
Li Jin et al., 2015	n = 70 age：2~8	n = 71 age：2~8	electrical pain	forearm	pain threshold	Asia	ASD high pain threshold, low pain sensitivity↓
Yasuda et al., 2016	n = 15 age：25.8 ± 9.2	n = 15 age：26.3 ± 7.5	cold pain heat pain electrical pain	forearm	pain threshold pain tolerance pain intensity rating	Asia	Pain threshold and tolerance: no significant difference? Pain intensity rating: ASD low pain intensity rating ↓
Fründt et al., 2017	n = 13 age：31.7 ± 8.2	n = 13 age：32.1 ± 7.1	cold pain heat pain pressure pain mechanical pain	dorsum of the right and left hands	pain threshold	Europe	no significant difference?
Vaughan et al., 2019	n = 13 age：27.2 ± 9.2	n = 13 age：27.1 ± 8.1	cold pain heat pain pressure pain mechanical pain cold pressure pain	palm (pressure pain) hand (cold pressure pain) mean of hand, foot and face (other modality)	pain threshold pain tolerance (cold pressure pain)	America	no significant difference?
Tordjman et al., 2009	n = 63 age：11.7 ± 4.5	n = 11 age：12.7 ± 5.9	venipuncture	arm	physiological response (heart rate)	Europe	ASD showed significantly greater physiological responses↑
Rattaz et al., 2013	n = 35 age：4.8	n = 36 age：3.7	venipuncture	arm	physiological response (heart rate)	Europe	ASD showed significantly greater physiological responses↑
Li Jin et al., 2015	n = 68 age：2~8	n = 64 age：2~8	venipuncture	arm	physiological response (heart rate)	Asia	ASD showed significantly greater physiological responses↑

Research	Sample size and age of ASD group	Sample size and age of control group	Pain modality	Pain location	Outcomes	Region	Results
Fan et al., 2014	n = 24 age：18.4 ± 2.8	n = 21 age：19.3 ± 3.4	pressure pain	left and right hands (proximal phalanx dorsally of index finger)	pain threshold	Asia	ASD low pain threshold, high pain sensitivity↑
Chen et al., 2017	n = 37 age：18.2 ± 5.2	n = 34 age：19.3 ± 4.6	pressure pain	left and right hands (proximal phalanx dorsally of index finger)	pain threshold	Asia	ASD low pain threshold, high pain sensitivity↑
Riquelme et al., 2016	n = 27 age：6.3 ± 3.2	n = 30 age：6.5 ± 3.4	pressure pain	Face dorsum of hand palm	pain threshold	Europe	ASD low pain threshold, high pain sensitivity↑
Chien et al., 2017	n = 31 age：20.5 ± 5.2	n = 22 age：21.4 ± 2.6	heat pain	leg (lateral)	pain intensity rating	Asia	no significant difference?
Failla et al., 2018	n = 15 age：27.5 ± 10.3	n = 16 age：30.1 ± 10.9	heat pain	leg (lateral)	pain threshold pain intensity rating	America	no significant difference?
Dubois et al., 2020	n = 19 age：31.5 ± 8.5	n = 19 age：31.6 ± 8.4	heat pain	forearm	pain intensity rating	Europe	no significant difference?
Cascio et al., 2008	n = 8 age：29.3 ± 10.5	n = 8 age：29.0 ± 9.7	cold pain heat pain	forearm palm	pain threshold	America	ASD low pain threshold, high pain sensitivity↑
Duerden et al., 2015	n = 20 age：14.6 ± 1.9	n = 55 age：15.7 ± 1.1	cold pain heat pain	forearm	pain threshold	America	no significant difference?
Bird et al., 2010	n = 18 age：34.6 ± 13.3	n = 18 age：35 ± 12.8	electrical pain	dorsum of hand	pain threshold	Europe	no significant difference?
Thaler et al., 2018	n = 16 age：25.5 ± 5.4	n = 16 age：24.5 ± 2.7	electrical pain	dorsum of hand	pain threshold pain intensity rating	Europe	no significant difference?
Li Jin et al., 2015	n = 70 age：2~8	n = 71 age：2~8	electrical pain	forearm	pain threshold	Asia	ASD high pain threshold, low pain sensitivity↓
Yasuda et al., 2016	n = 15 age：25.8 ± 9.2	n = 15 age：26.3 ± 7.5	cold pain heat pain electrical pain	forearm	pain threshold pain tolerance pain intensity rating	Asia	Pain threshold and tolerance: no significant difference? Pain intensity rating: ASD low pain intensity rating ↓
Fründt et al., 2017	n = 13 age：31.7 ± 8.2	n = 13 age：32.1 ± 7.1	cold pain heat pain pressure pain mechanical pain	dorsum of the right and left hands	pain threshold	Europe	no significant difference?
Vaughan et al., 2019	n = 13 age：27.2 ± 9.2	n = 13 age：27.1 ± 8.1	cold pain heat pain pressure pain mechanical pain cold pressure pain	palm (pressure pain) hand (cold pressure pain) mean of hand, foot and face (other modality)	pain threshold pain tolerance (cold pressure pain)	America	no significant difference?
Tordjman et al., 2009	n = 63 age：11.7 ± 4.5	n = 11 age：12.7 ± 5.9	venipuncture	arm	physiological response (heart rate)	Europe	ASD showed significantly greater physiological responses↑
Rattaz et al., 2013	n = 35 age：4.8	n = 36 age：3.7	venipuncture	arm	physiological response (heart rate)	Europe	ASD showed significantly greater physiological responses↑
Li Jin et al., 2015	n = 68 age：2~8	n = 64 age：2~8	venipuncture	arm	physiological response (heart rate)	Asia	ASD showed significantly greater physiological responses↑

Research	Sample size	Pain modality	ASD group	control group	p
Yasuda et al., 2016	15 vs 15	Contact cold pain	2.50 ± 7.22 ℃	3.74 ± 11.24 ℃	0.66
		Contact heat pain	46.12 ± 2.23 ℃	46.35 ± 3.16 ℃	0.66
		Electrical pain	104.48 ± 52.23 μA	92.86 ± 55.99 μA	0.47
Vaughan et al., 2019	13 vs 13	Cold pressure pain	37.28 ± 45.49 s	28.24 ± 17.87 s	0.51

Research	Sample size	Pain modality	ASD group	control group	p
Yasuda et al., 2016	15 vs 15	Contact cold pain	2.50 ± 7.22 ℃	3.74 ± 11.24 ℃	0.66
		Contact heat pain	46.12 ± 2.23 ℃	46.35 ± 3.16 ℃	0.66
		Electrical pain	104.48 ± 52.23 μA	92.86 ± 55.99 μA	0.47
Vaughan et al., 2019	13 vs 13	Cold pressure pain	37.28 ± 45.49 s	28.24 ± 17.87 s	0.51

Moderators	heterogeneity			Pain modality	sample	Effect value and 95% confidence interval			Bilateral examination p
Moderators	Q_B	df	p	Pain modality	sample	estimate	Lower	Upper	Bilateral examination p
Pain modality	10.90	4	p < 0.05	Cold Pain	6	0.17	-0.16	0.51	0.31
				Heat pain	6	-0.05	-0.58	0.49	0.86
				Pressure pain	5	1.62	0.46	2.77	0.006
				Mechanical pain	2	-0.43	-0.98	0.12	0.13
				Electrical pain	4	-0.27	-1.37	0.82	0.63
Pain location	3.46	3	0.33	Hand	10	0.41	-0.24	1.06	0.22
				Arm	6	0.78	-0.34	2.2	0.43
				Leg	1	0.22	-0.98	0.42	0.54
				Multiple body sites	6	0.93	-0.49	0.93	0.15
Sample size of ASD group	79.26	3	p < 0.001	n ≤ 10	2	1.54	0.72	2.36	p < 0.001
				10 < n ≤ 20	16	-0.04	-0.24	0.15	0.65
				20 < n ≤ 50	4	1.86	0.39	3.33	0.01
				n > 50	1	-1.61	-1.99	-1.23	p < 0.001
Age of the ASD group	6.90	3	0.08	Children only	2	0.81	-3.94	5.55	0.74
				Adolescents only	2	-0.28	-0.64	0.09	0.14
				Adolescents and adults	6	0.89	0.06	1.72	0.04
				Adults	13	0.07	-0.26	0.40	0.66
Region	0.44	2	0.80	Asia	6	0.57	-0.81	1.96	0.42
				America	10	0.14	-0.25	0.53	0.48
				Europe	7	0.33	-0.58	1.23	0.48