Electroacupuncture Intensity and Chronic Pain in Knee OA

Table 1. Baseline characteristics of participants
Variable	Strong EA (n = 145)	Weak EA (n = 72)	Sham EA (n = 75)
Female, no. (%)	106 (73.1)	57 (79.2)	60 (80.0)
Age, mean (SD), years	64.6 (10.2)	63.7 (9.3)	61.9 (9.5)
Symptom duration, years (%)
< 0.5 years	51 (35.2)	27 (37.5)	27 (36.0)
0.5 to 3 years	60 (41.4)	27 (37.5)	23 (30.7)
3 to 5 years	14 (9.7)	8 (11.1)	15 (20.0)
≥ 5 years	20 (13.8)	10 (13.9)	10 (13.3)
Height, mean (SD), m	1.62 (0.07)	1.62 (0.07)	1.64 (0.08)
Weight, mean (SD), kg	59.8 (7.8)	59.4 (7.5)	61.8 (8.5)
BMI, mean (SD)	22.67 (2.22)	22.46 (1.87)	22.93 (1.86)
Previous treatment, no. of patients (%)
Physical therapy	25 (17.2)	11 (15.3)	12 (16.0)
Corticosteroid injections	5 (3.5)	2 (2.8)	2 (2.7)
Acupuncture	21 (14.5)	8 (10.8)	10 (13.3)
Exercise	36 (24.8)	15 (20.3)	16 (21.3)

BMI body mass index

Table 2. Primary and secondary outcome measurements of intention-to-treat analysis during the entire study
Outcome	Strong EA	Weak EA	Sham EA	Pairwise comparison
				Strong EA vs. sham EA		Weak EA vs. sham EA		Strong EA vs. weak EA
				Effect size (95% CI)	P value	Effect size (95% CI)	P value	Effect size (95% CI)	P value
Primary outcome
CPM, mean (SD)^a
Weeks 0–1	0.64 (0.16)	0.12 (0.27)	0.44 (0.24)	0 (0 to 0)	.33	0 (− 0.31 to 0.32)	0.98	0.15 (− 0.13 to 0.42)	.29
Weeks 0–2	14.85 (0.16)	4.75 (0.28)	1.43 (0.24)	13.54 (13.23 to 13.85)	< .01	3.80 (3.45 to 4.15)	< .01	9.73 (9.44 to 10.02)	< .01
VAS, mean (SD)^b
Weeks 0–1	− 1.34 (0.10)	− 1.52 (0.14)	0.65 (0.14)	− 0.58 (− 0.71 to − 0.44)	< .01	− 0.77 (− 0.93 to − 0.62)	< .01	0.19 (0.04 to 0.35)	.01
Weeks 0–2	− 2.97 (0.10)	− 2.75 (0.15)	1.19 (0.14)	− 1.58 (− 1.75 to − 1.4)	< .01	− 1.36 (− 1.57 to − 1.16)	< .01	− 0.22 (− 0.42 to − 0.03)	.03
WOMAC, mean (SD)^c
Weeks 0–1	− 13.03 (0.56)	− 13.06 (0.87)	− 3.47 (0.80)	− 9.35 (− 10.75 to − 7.96)	< .01	− 9.66 (− 11.26 to − 8.07)	< .01	0.18 (− 1.23 to 1.59)	.80
Weeks 0–2	− 20.92 (0.56)	− 20.55 (0.89)	− 8.87 (0.81)	− 11.70 (− 12.52 to − 10.89)	< .01	− 11.55 (− 12.52 to − 10.58)	< .01	− 0.15 (− 1.06 to 0.75)	.74
Secondary outcome
NPRS, mean (SD)^c
Weeks 0–1	− 1.59 (0.10)	1.12 (0.14)	0.72 (0.14)	− 0.93 (− 1.1 to − 0.76)	< .01	− 0.69 (− 0.9 to − 0.49)	< .01	− 0.11 (− 0.3 to − 0.07)	.24
Weeks 0–2	− 2.97 (0.11)	2.48 (0.14)	1.40 (0.14)	− 1.55 (− 1.76 to − 1.33)	< .01	− 1.07 (− 1.31 to − 0.83)	< .01	− 0.47 (− 0.7 to − 0.24)	< .01
ES, mean (SD)^c
Weeks 0–1	− 1.69 (0.12)	− 1.36 (0.16)	0.71 (0.13)	− 0.91 (− 1.09 to − 0.73)	< .01	− 0.67 (− 0.88 to − 0.45)	< .01	− 0.3 (− 0.5 to − 0.1)	< .01
Weeks 0–2	− 3.28 (0.13)	− 2.56 (0.16)	1.24 (0.13)	− 1.88 (− 2.12 to − 1.65)	< .01	− 1.22 (− 1.49 to − 0.95)	< .01	− 0.67 (− 0.92 to − 0.42)	< .01
PPI, mean (SD)^c
Weeks 0–1	− 0.70 (0.07)	− 0.68 (0.09)	0.29 (0.09)	− 0.44 (− 0.58 to − 0.29)	< .01	− 0.45 (− 0.62 to − 0.28)	< .01	0.04 (− 0.11 to 0.19)	.59
Weeks 0–2	− 1.46 (0.07)	− 1.39 (0.09)	0.65 (0.09)	− 0.78 (− 0.96 to − 0.6)	< .01	− 0.82 (− 1.03 to − 0.6)	< .01	0.04 (− 0.16 to 0.24)	.72

EA electroacupuncture, VAS visual analog scale, CPM conditioned pain modulation, WOMAC Western Ontario and McMaster Universities Osteoarthritis Index, NPRS numeric pain rating scale, ES emotional scale, PPI present pain intensity
^aHigher values indicate better status
^bRating scales 0 to 10, with 0 being no pain and 10 being excruciating
^cLower values indicate better status

Table S1. Descriptive statistics of mean (SD) scores on outcome measures over time according to group.
Outcome	Strong EA	Weak EA	Sham EA
Primary outcome
CPM, mean (SD) ^a
Week 0 (Baseline)	9.49 (1.90)	9.86 (2.50)	9.46 (2.05)
Week 1	10.13 (0.97)	9.99 (1.02)	9.90 (1.00)
Week 2	24.34 (0.87)	14.61 (0.79)	10.89(1.07)
VAS, mean (SD) ^b
Week 0 (Baseline)	7.50 (0.91)	7.54 (0.99)	7.23 (0.97)
Week 1	6.16 (0.86)	6.02 (0.86)	6.58 (0.83)
Week 2	4.53 (0.84)	4.79 (0.66)	6.04 (0.75)
WOMAC, mean (SD) ^c
Week 0 (Baseline)	31.86 (4.67)	31.82 (5.96)	31.80 (5.49)
Week 1	18.83 (5.98)	18.76 (5.98)	28.33 (6.06)
Week 2	10.94 (2.93)	11.27 (2.79)	22.93 (2.04)
Secondary outcome
NPRS, mean (SD) ^c
Week 0 (Baseline)	6.83 (0.96)	6.69 (0.94)	6.91 (1.02)
Week 1	5.25 (0.82)	5.28 (0.75)	6.19 (0.80)
Week 2	3.87 (0.87)	4.22 (0.72)	5.51 (0.67)
ES, mean (SD) ^c
Week 0 (Baseline)	6.76 (1.16)	6.61 (1.03)	6.57 (0.92)
Week 1	5.07 (1.00)	5.25 (0.83)	5.87 (0.79)
Week 2	3.48 (0.98)	4.05 (0.93)	5.34 (0.67)
PPI, mean (SD) ^c
Week 0 (Baseline)	3.46 (0.59)	3.36 (0·54)	3.49 (0.53)
Week 1	2.75 (0.58)	2.68 (0.55)	3.20 (0.52)
Week 2	1.99 (0.65)	1.97 (0.50)	2.85 (0.55)

Abbreviations: EA, electroacupuncture; VAS, visual analog scale; CPM, conditioned pain modulation; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index; NPRS, numeric pain rating scale; ES, emotional scale; PPI, present pain intensity.
^a Higher values indicate better status.
^b Rating scale 0 to 10, with 0 being no pain and 10 being excruciating.
^c Lower values indicate better status.

Table S2. Primary and Secondary Outcome Measurements of Per-protocol Analysis During the Entire Study.
Outcome	Pairwise Comparison
	Strong EA vs. Sham EA		Weak EA vs. Sham EA		Strong EA vs. Weak EA
	Effect Size (95% CI)	P value	Effect Size (95% CI)	P value	Effect Size (95% CI)	P value
Primary outcome
CPM, mean (SD) ^a
Week 0–1	0.36 (0.08 to 0.63)	.01	-0.19 (-0.12 to 0.51)	0.23	0.15 (-0.13 to 0.42)	.29
Week 0–2	13.54 (13.23 to 13.85)	<.01	3.80 (3.45 to 4.15)	<.01	9.73 (9.47 to 10.00)	<.01
VAS, mean (SD) ^b
Week 0–1	-0.65 (-0.79 to -0.51)	<.01	-0.83 (-0.99 to -0.67)	<.01	0.19 (0.04 to 0.35)	.01
Week 0–2	-1.58 (-1.75 to -1.4)	<.01	-1.36 (-1.57 to -1.16)	<.01	-0.25 (-0.44 to -0.07)	.01
WOMAC, mean (SD) ^c
Week 0–1	-9.47 (-10.83 to -8.10)	<.01	-9.79 (-11.37 to -8.20)	<.01	0.18 (-1.23 to 1.59)	.80
Week 0–2	-11.70 (-12.52 to -10.89)	<.01	-11.55 (-12.52 to -10.58)	<.01	-0.16 (-0.99 to 0.75)	.70
Secondary outcome
NPRS, mean (SD) ^c
Week 0–1	-0.98 (-1.15 to -0.82)	<.01	-0.82 (-1.01 to -0.63)	<.01	-0.11 (-0.30 to -0.07)	.24
Week 0–2	-1.55 (-1.76 to -1.33)	<.01	-1.07 (-1.31 to -0.83)	<.01	-0.48 (-0.70 to -0.27)	<.01
ES, mean (SD) ^c
Week 0–1	-0.94 (-1.11 to -0.77)	<.01	-0.66 (-0.86 to -0.46)	<.01	-0.30 (-0.50 to -0.1)	<.01
Week 0–2	-1.88 (-2.12 to -1.65)	<.01	-1.22 (-1.49 to -0.95)	<.01	-0.67 (-0.91 to -0.44)	<.01
PPI, mean (SD) ^c
Week 0–1	-0.57 (-0.72 to -0.42)	<.01	-0.56 (-0.74 to -0.39)	<.01	0.04 (-0.11 to 0.19)	.59
Week 0–2	-0.78 (-0.96 to -0.6)	<.01	-0.82 (-1.03 to -0.6)	<.01	0.05 (-0.13 to 0.24)	.58

Abbreviations: EA, electroacupuncture; VAS, visual analog scale; CPM, conditioned pain modulation; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index; NPRS, numeric pain rating scale; ES, emotional scale; PPI, present pain intensity.
^a Higher values indicate better status.
^b Rating scale 0 to 10, with 0 being no pain and 10 being excruciating.
^c Lower values indicate better status.

Authors and Disclosures

Zheng-tao Lv^1,2†, Lin-lin Shen^3†, Bing Zhu^4†, Zhao-qing Zhang^5†, Chao-yang Ma^6†, Guo-fu Huang^3†, Jing Yin^5†, Ling-ling Yu^1,3†, Si-yi Yu^7†, Ming-qiao Ding⁸, Jing Li⁹, Xiao-cui Yuan¹, Wei He⁴, Xiang-hong Jing⁴* and Man Li¹*

¹Department of Neurobiology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China. ²Department of Orthopedics, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China. ³Combined Traditional Chinese and Western Medicine Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China. ⁴Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, China. ⁵The Third Hospital of Wuhan, Wuhan 430060, China. ⁶Central Hospital of Wuhan, Wuhan 430014, China. ⁷School of Acupuncture and Moxibustion, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China. ⁸The Fifth Hospital of Wuhan, Wuhan 430050, China. ⁹Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
^†Zheng-tao Lv, Lin-lin Shen, Bing Zhu, Zhao-qing Zhang, Chao-yang Ma,
Guo-fu Huang, Jing Yin, Ling-ling Yu, and Si-yi Yu contributed equally to this work and should be considered co-first authors.

* Correspondence
jxhtjb@263.net; liman73@mails.tjmu.edu.cn

Authors' contributions
ML had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. ZTL, SYY, BZ, and LLS participated in the data collection and drafting of the manuscript. ZQZ, CYM, and GFH participated in the data collection and oversaw the recruitment and treatment of participants in each center. JY and LLY were responsible for the statistical analysis and acquisition of the data. MQD and JL oversaw the details of the study, including its accuracy and integrity. XCY and WH critically revised the manuscript. ML and XHJ participated in the conception and design and critical revision of the manuscript. All authors read and approved the final manuscript.

Competing interests
The authors declare that they have no competing interests.