自闭症谱系障碍个体的疼痛敏感性异常：来自元分析的证据

doi:10.3724/SP.J.1041.2021.00613

摘要/Abstract

摘要：

本研究采用元分析方法, 以疼痛阈限、疼痛诱发生理反应和疼痛评分为结果变量, 考察了自闭症谱系障碍个体(Autism Spectrum Disorder, ASD)的疼痛敏感性异常, 以期为ASD的诊断和干预提供参考。元分析共纳入16项研究(总样本量N = 822)。对于疼痛阈限, ASD组和对照组无显著差异, 但受到疼痛模态等变量的调节作用, 如ASD组的压力疼痛阈限显著低于对照组。对于疼痛诱发生理反应, ASD组对现实医疗疼痛的生理反应强于对照组。然而, ASD组和对照组在疼痛评分上无显著差异。将来研究应结合多模态疼痛刺激和多维度疼痛评估, 系统考察ASD个体的疼痛敏感性及其与临床核心症状之间的联系。

关键词: 自闭症谱系障碍, 疼痛敏感性, 元分析, 疼痛阈限, 疼痛诱发生理反应

Abstract:

Pain is defined as an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage. Pain is of vital functional significance, as it signals threat and initiates behavioral adaptations to avoid harm so as to protect the body. Previous studies have shown abnormalities in pain sensitivity among individuals with autism spectrum disorder (ASD), which have been associated with their clinical core symptoms, including restricted and repetitive behaviors as well as deficits in social behaviors. Evidence from case studies and surveys suggested the hyposensitivity to pain for individuals with ASD. Nevertheless, results from experimental studies that involved the application of noxious stimulations and psychophysical measurements were heterogeneous, e.g., some studies reported hypersensitivity to pain in ASD individuals, others reported their hyposensitivity or even normal sensitivity to pain.

These results suggest that the abnormalities of pain sensitivity among individuals with ASD were modality-dependent, with the abnormality selectively applicable to pressure pain or medical pain. Future studies should combine behavioral, physiological, and neuroimaging measures to comprehensively investigate the pain sensitivity profiles of individuals with ASD. The potential link between pain sensitivity and clinical core symptoms among individuals with ASD should be characterized. Relevant results would potentially expand our understanding of ASD neurobiological mechanisms and provide the theoretical basis for pain assessment among individuals with ASD.

In this study, we utilized a meta-analysis approach to systematically review experimental studies that investigated pain sensitivity among individuals with ASD and were published before August 10, 2020. The meta-analysis was performed according to the rigorous PRISMA Protocol. Studies were included in the analysis if they included both clearly diagnosed ASD individuals and healthy controls, reported data relevant to pain sensitivity, including pain threshold, pain tolerance, pain ratings, and pain-evoked physiological responses. Relevant studies were obtained from databases including China National Knowledge Infrastructure, Web of Science, PsycInfo, and PubMed by searching for keywords including pain, nociception, autis*, and Asperger. The meta-analysis was conducted in STATA 12, and the effect sizeHedge's g with ±95% confidence intervals (CIs) was calculated using a random effect statistical model. Further, we assessed possible moderating effects from variables of pain modality, pain site, the age of involved participants, the sample size of the ASD group and sample locations.

Sixteen experimental studies were included in the meta-analysis, with a total sample size N = 822. Pain threshold was not significantly different between ASD individuals and healthy controls (g = 0.34, 95% CI = [-0.14, 0.82]), and this estimate was moderated by variables of pain modality, the age of involved participants, and the sample size of the ASD group. Specifically, individuals with ASD exhibited lower pain thresholds than those of healthy controls selectively for pressure pain (g = 1.62, 95% CI = [0.46, 2.77]). For the outcome variable of pain evoked physiological response, individuals with ASD showed significantly greater physiological responses to medical procedures than those of healthy controls (g= 2.87, 95% CI = [1.07, 4.67]). Nevertheless, ASD and control groups had comparable pain ratings (g = -0.26, 95% CI = [-0.64, 0.11]).

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

中图分类号:

R395

张文芸, 李晓云, 姚俊杰, 叶倩, 彭微微. (2021). 自闭症谱系障碍个体的疼痛敏感性异常：来自元分析的证据. 心理学报, 53(6), 613-628.

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.

图/表 7

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研究	ASD组样本量及年龄(岁)	对照组样本量及年龄(岁)	刺激模态	刺激位置	疼痛测量指标	地区	主要结果
Fan et al. 2014	n = 24 年龄：18.4 ± 2.8	n = 21 年龄：19.3 ± 3.4	压力疼痛	左右手(食指背侧近端指骨)	疼痛阈限	亚洲	ASD低疼痛阈限, 高疼痛敏感性↑
Chen et al. 2017	n = 37 年龄：18.2 ± 5.2	n = 34 年龄：19.3 ± 4.6	压力疼痛	左右手(食指背侧近端指骨)	疼痛阈限	亚洲	ASD低疼痛阈限, 高疼痛敏感性↑
Riquelme et al. 2016	n = 27 年龄：6.3 ± 3.2	n = 30 年龄：6.5 ± 3.4	压力疼痛	脸、手背和手掌	疼痛阈限	欧洲	ASD低疼痛阈限, 高疼痛敏感性↑
Chien et al. 2017	n = 31 年龄：20.5 ± 5.2	n = 22 年龄：21.4 ± 2.6	热痛	腿(外侧)	疼痛评分	亚洲	无显著差异?
Failla et al. 2018	n = 15 年龄：27.5 ± 10.3	n = 16 年龄：30.1 ± 10.9	热痛	腿(外侧)	疼痛阈限疼痛评分	美洲	无显著差异?
Dubois et al. 2020	n = 19 年龄：31.5 ± 8.5	n = 19 年龄：31.6 ± 8.4	热痛	手臂	疼痛评分	欧洲	无显著差异?
Cascio et al. 2008	n = 8 年龄：29.3 ± 10.5	n = 8 年龄：29.0 ± 9.7	冷痛热痛	前臂手掌	疼痛阈限	美洲	ASD低疼痛阈限, 高疼痛敏感性↑
Duerden et al. 2015	n = 20 年龄：14.6 ± 1.9	n = 55 年龄：15.7 ± 1.1	冷痛热痛	前臂	疼痛阈限	美洲	无显著差异?
Bird et al. 2010	n = 18 年龄：34.6 ± 13.3	n = 18 年龄：35 ± 12.8	电刺激疼痛	手背	疼痛阈限	欧洲	无显著差异?
Thaler et al. 2018	n = 16 年龄：25.5 ± 5.4	n = 16 年龄：24.5 ± 2.7	电刺激疼痛	手背	疼痛阈限疼痛评分	欧洲	无显著差异?
李晋等, 2015	n = 70 年龄：2~8	n = 71 年龄：2~8	电刺激疼痛	前臂	疼痛阈限	亚洲	ASD高疼痛阈限, 低疼痛敏感性↓
Yasuda et al. 2016	n = 15 年龄：25.8 ± 9.2	n = 15 年龄：26.3 ± 7.5	冷痛热痛电刺激疼痛	前臂	疼痛阈限耐受阈限疼痛评分	亚洲	疼痛阈限和耐受阈限：无显著差异? 疼痛评分： ASD低疼痛评分↓
Fründtet al. 2017	n = 13 年龄：31.7 ± 8.2	n = 13 年龄：32.1 ± 7.1	冷痛热痛压力疼痛机械疼痛	左右手背	疼痛阈限	欧洲	无显著差异?
Vaughan et al. 2019	n = 13 年龄：27.2 ± 9.2	n = 13 年龄：27.1 ± 8.1	冷痛热痛冷水压痛机械疼痛压力疼痛	手掌(压痛) 手部(冷水压痛) 手、脚和脸均值 (其他剩余模态)	疼痛阈限耐受阈限 (冷压痛)	美洲	无显著差异?
Tordjman et al. 2009	n = 63 年龄：11.7 ± 4.5	n = 11 年龄：12.7 ± 5.9	静脉穿刺	手臂	生理反应 (心率)	欧洲	ASD生理反应强烈↑, 心率变化大
Rattaz et al. 2013	n = 35 年龄：4.8	n = 36 年龄：3.7	静脉穿刺	手臂	生理反应 (心率)	欧洲	ASD生理反应强烈↑, 心率变化大
李晋等, 2015	n = 68 年龄：2~8	n = 64 年龄：2~8	静脉穿刺	手臂	生理反应 (心率)	亚洲	ASD生理反应强烈↑, 心率变化大

研究	ASD组样本量及年龄(岁)	对照组样本量及年龄(岁)	刺激模态	刺激位置	疼痛测量指标	地区	主要结果
Fan et al. 2014	n = 24 年龄：18.4 ± 2.8	n = 21 年龄：19.3 ± 3.4	压力疼痛	左右手(食指背侧近端指骨)	疼痛阈限	亚洲	ASD低疼痛阈限, 高疼痛敏感性↑
Chen et al. 2017	n = 37 年龄：18.2 ± 5.2	n = 34 年龄：19.3 ± 4.6	压力疼痛	左右手(食指背侧近端指骨)	疼痛阈限	亚洲	ASD低疼痛阈限, 高疼痛敏感性↑
Riquelme et al. 2016	n = 27 年龄：6.3 ± 3.2	n = 30 年龄：6.5 ± 3.4	压力疼痛	脸、手背和手掌	疼痛阈限	欧洲	ASD低疼痛阈限, 高疼痛敏感性↑
Chien et al. 2017	n = 31 年龄：20.5 ± 5.2	n = 22 年龄：21.4 ± 2.6	热痛	腿(外侧)	疼痛评分	亚洲	无显著差异?
Failla et al. 2018	n = 15 年龄：27.5 ± 10.3	n = 16 年龄：30.1 ± 10.9	热痛	腿(外侧)	疼痛阈限疼痛评分	美洲	无显著差异?
Dubois et al. 2020	n = 19 年龄：31.5 ± 8.5	n = 19 年龄：31.6 ± 8.4	热痛	手臂	疼痛评分	欧洲	无显著差异?
Cascio et al. 2008	n = 8 年龄：29.3 ± 10.5	n = 8 年龄：29.0 ± 9.7	冷痛热痛	前臂手掌	疼痛阈限	美洲	ASD低疼痛阈限, 高疼痛敏感性↑
Duerden et al. 2015	n = 20 年龄：14.6 ± 1.9	n = 55 年龄：15.7 ± 1.1	冷痛热痛	前臂	疼痛阈限	美洲	无显著差异?
Bird et al. 2010	n = 18 年龄：34.6 ± 13.3	n = 18 年龄：35 ± 12.8	电刺激疼痛	手背	疼痛阈限	欧洲	无显著差异?
Thaler et al. 2018	n = 16 年龄：25.5 ± 5.4	n = 16 年龄：24.5 ± 2.7	电刺激疼痛	手背	疼痛阈限疼痛评分	欧洲	无显著差异?
李晋等, 2015	n = 70 年龄：2~8	n = 71 年龄：2~8	电刺激疼痛	前臂	疼痛阈限	亚洲	ASD高疼痛阈限, 低疼痛敏感性↓
Yasuda et al. 2016	n = 15 年龄：25.8 ± 9.2	n = 15 年龄：26.3 ± 7.5	冷痛热痛电刺激疼痛	前臂	疼痛阈限耐受阈限疼痛评分	亚洲	疼痛阈限和耐受阈限：无显著差异? 疼痛评分： ASD低疼痛评分↓
Fründtet al. 2017	n = 13 年龄：31.7 ± 8.2	n = 13 年龄：32.1 ± 7.1	冷痛热痛压力疼痛机械疼痛	左右手背	疼痛阈限	欧洲	无显著差异?
Vaughan et al. 2019	n = 13 年龄：27.2 ± 9.2	n = 13 年龄：27.1 ± 8.1	冷痛热痛冷水压痛机械疼痛压力疼痛	手掌(压痛) 手部(冷水压痛) 手、脚和脸均值 (其他剩余模态)	疼痛阈限耐受阈限 (冷压痛)	美洲	无显著差异?
Tordjman et al. 2009	n = 63 年龄：11.7 ± 4.5	n = 11 年龄：12.7 ± 5.9	静脉穿刺	手臂	生理反应 (心率)	欧洲	ASD生理反应强烈↑, 心率变化大
Rattaz et al. 2013	n = 35 年龄：4.8	n = 36 年龄：3.7	静脉穿刺	手臂	生理反应 (心率)	欧洲	ASD生理反应强烈↑, 心率变化大
李晋等, 2015	n = 68 年龄：2~8	n = 64 年龄：2~8	静脉穿刺	手臂	生理反应 (心率)	亚洲	ASD生理反应强烈↑, 心率变化大

研究	样本量	刺激模态	ASD 个体	普通个体	p
Yasuda et al. 2016	15 vs 15	接触式冷痛	2.50 ± 7.22 ℃	3.74 ± 11.24 ℃	0.66
		接触式热痛	46.12 ± 2.23 ℃	46.35 ± 3.16 ℃	0.66
		电刺激疼痛	104.48 ± 52.23 μA	92.86 ± 55.99 μA	0.47
Vaughan et al. 2019	13 vs 13	冷压痛	37.28 ± 45.49 s	28.24 ± 17.87 s	0.51

研究	样本量	刺激模态	ASD 个体	普通个体	p
Yasuda et al. 2016	15 vs 15	接触式冷痛	2.50 ± 7.22 ℃	3.74 ± 11.24 ℃	0.66
		接触式热痛	46.12 ± 2.23 ℃	46.35 ± 3.16 ℃	0.66
		电刺激疼痛	104.48 ± 52.23 μA	92.86 ± 55.99 μA	0.47
Vaughan et al. 2019	13 vs 13	冷压痛	37.28 ± 45.49 s	28.24 ± 17.87 s	0.51

调节变量	同质性分析			类别	独立样本	效应值及95%置信区间			双侧检验 p
调节变量	Q_B	df	p	类别	独立样本	点估计	下限	上限	双侧检验 p
刺激模态	10.90	4	p< 0.05	冷痛	6	0.17	-0.16	0.51	0.31
				热痛	6	-0.05	-0.58	0.49	0.86
				压力痛	5	1.62	0.46	2.77	0.006
				机械痛	2	-0.43	-0.98	0.12	0.13
				电刺激疼痛	4	-0.27	-1.37	0.82	0.63
刺激位置	3.46	3	0.33	手部	10	0.41	-0.24	1.06	0.22
				手臂	6	0.78	-0.34	2.2	0.43
				腿部	1	0.22	-0.98	0.42	0.54
				多部位均值	6	0.93	-0.49	0.93	0.15
ASD组样本量	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
被试群体	6.90	3	0.08	儿童	2	0.81	-3.94	5.55	0.74
				青少年	2	-0.28	-0.64	0.09	0.14
				青少年与成人	6	0.89	0.06	1.72	0.04
				成人	13	0.07	-0.26	0.40	0.66
地区	0.44	2	0.80	亚洲	6	0.57	-0.81	1.96	0.42
				美洲	10	0.14	-0.25	0.53	0.48
				欧洲	7	0.33	-0.58	1.23	0.48