Transcranial Direct Current Stimulation Alleviates Endometriosis-Related Pain by Inhibiting NLRP3 Inflammasome Activation

doi:10.12280/gjfckx.20260056

Abstract

Abstract:

Objective: To evaluate the therapeutic efficacy of transcranial direct current stimulation (tDCS) on endometriosis (EMs)-related pain and explore its potential mechanism involving the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3) inflammasome pathway. Methods: From January 2024 to June 2025, 40 patients with EMs-related chronic pelvic pain admitted to Beijing Chao-Yang Hospital, Capital Medical University were selected and randomly divided into a tDCS group (n=20) and a sham stimulation control group (n=20) using a random number table. The tDCS group received stimulation with the anode placed over the F3 area and the cathode over the contralateral supraorbital Fp2 area, with a current intensity of 2 mA, once daily for 20 minutes per session, for 10 consecutive days. The sham stimulation control group had electrode placed in identical position as the tDCS group, but with a current intensity of 0 mA. Pain levels were assessed using the visual analogue scale (VAS) before treatment and 10 days after treatment completion. Serum levels of the downstream factors of NLRP3 inflammasome activation, interleukin-1β (IL-1β), IL-18 and lactate dehydrogenase (LDH), were measured by enzyme-linked immunosorbent assay (ELISA) before and 10 days after treatment. Data analysis was performed using GraphPad Prism 5.0 software. Results: There were no statistically significant differences between the two groups in age, gravidity, parity, or baseline VAS scores (all P>0.05). After treatment, the VAS score in the tDCS group was significantly lower than that in the sham stimulation control group (t=8.953, P<0.001). ELISA results showed that serum levels of IL-1β, IL-18, and LDH in the tDCS group were significantly lower than those in the sham stimulation control group after treatment (all P<0.05). Correlation analysis revealed that in the tDCS group, the post-treatment VAS score was significantly positively correlated with serum IL-1β (r=0.512, P=0.021) and LDH levels (r=0.580, P=0.007), but not with IL-18 levels (P=0.073). No significant correlations were observed before treatment (all P>0.05). Conclusions: tDCS effectively alleviate EMs-related pain. Its mechanism may be related to the inhibition of NLRP3 inflammasome activation, reduction in the release of downstream pro-inflammatory cytokines, and attenuation of pyroptosis. Furthermore, the degree of pain relief after treatment is directly associated with the reduction in inflammatory factors and cellular damage indicatiors.

Key words: Transcranial direct current stimulation, Endometriosis, Dysmenorrhea, NLR family, pyrin domain-containing 3 protein, Interleukins

ZHENG Ping, ZHAO Li-ming, ZHANG Xue-fang, GU Bin, YOU Ai-hong, LANG Jing-he, LENG Jin-hua, LIU Chong-dong. Transcranial Direct Current Stimulation Alleviates Endometriosis-Related Pain by Inhibiting NLRP3 Inflammasome Activation[J]. Journal of International Obstetrics and Gynecology, 2026, 53(3): 352-356.

Figures/Tables 4

References 22

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组别	n	年龄（岁）	孕次	产次	VAS评分
组别	n	年龄（岁）	孕次	产次	基线	治疗后
tDCS组	20	38.0±2.3	2（1，3）	1（0，1）	7.45±0.32	3.80±0.26
假刺激对照组	20	37.0±2.1	2（1，3）	1（1，1）	7.35±0.30	7.35±0.30
t或Z		1.636	200.000	152.000	0.227	8.953
P		0.110	0.988	0.141	0.821	<0.001

组别	n	年龄（岁）	孕次	产次	VAS评分
组别	n	年龄（岁）	孕次	产次	基线	治疗后
tDCS组	20	38.0±2.3	2（1，3）	1（0，1）	7.45±0.32	3.80±0.26
假刺激对照组	20	37.0±2.1	2（1，3）	1（1，1）	7.35±0.30	7.35±0.30
t或Z		1.636	200.000	152.000	0.227	8.953
P		0.110	0.988	0.141	0.821	<0.001

组别	n	IL-1β（pg/mL）		IL-18（pg/mL）		LDH（U/L）
组别	n	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
tDCS组	20	20.74±0.80	10.30±0.69	253.20±12.62	151.10±9.09	496.80±17.02	241.00±17.54
假刺激对照组	20	19.73±0.89	18.18±0.83	260.70±11.05	247.50±13.11	539.30±26.69	531.20±25.68
t		0.887	7.295	0.449	6.042	1.345	9.332
P		0.381	<0.001	0.656	<0.001	0.187	<0.001

组别	n	IL-1β（pg/mL）		IL-18（pg/mL）		LDH（U/L）
组别	n	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
tDCS组	20	20.74±0.80	10.30±0.69	253.20±12.62	151.10±9.09	496.80±17.02	241.00±17.54
假刺激对照组	20	19.73±0.89	18.18±0.83	260.70±11.05	247.50±13.11	539.30±26.69	531.20±25.68
t		0.887	7.295	0.449	6.042	1.345	9.332
P		0.381	<0.001	0.656	<0.001	0.187	<0.001

时间点	VAS评分与血清炎症因子	r	P
治疗前	VAS与IL-1β	0.154	0.660
	VAS与IL-18	-0.003	0.991
	VAS与LDH	0.346	0.135
治疗后	VAS与IL-1β	0.512	0.021
	VAS与IL-18	0.410	0.073
	VAS与LDH	0.580	0.007