Efficacy and Proposed Mechanisms of Electroacupuncture in Animal Models of Chemotherapy-Induced Peripheral Neuropathy: A Systematic Review and Meta-Analysis

Mingjie Tang; Hang Xu; Shiyi Zheng; Yinghong Li; Tianyi Zhu; Zhongqi Xie; Zhaoming Chen

doi:10.2147/JPR.S641678

. 2026 Sep 29;19:641678. doi: 10.2147/JPR.S641678

Efficacy and Proposed Mechanisms of Electroacupuncture in Animal Models of Chemotherapy-Induced Peripheral Neuropathy: A Systematic Review and Meta-Analysis

Mingjie Tang ^1,^2,^*, Hang Xu ^1,^*, Shiyi Zheng ^1,^*, Yinghong Li ², Tianyi Zhu ¹, Zhongqi Xie ¹, Zhaoming Chen ^1,^✉

PMCID: PMC13635300 PMID: 42835105

Abstract

Background

Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting toxicity of chemotherapy with few effective treatment options. Electroacupuncture (EA) has demonstrated promising clinical efficacy, yet its preclinical evidence remains fragmented, limiting mechanistic understanding and translational application. This systematic review and meta-analysis evaluated the efficacy of EA in animal models of CIPN and synthesized the underlying mechanisms.

Methods

Seven databases were systematically searched from inception to June 24, 2026, for controlled animal studies investigating EA for CIPN. The primary outcome was mechanical withdrawal threshold (MWT); secondary outcomes included thermal withdrawal latency (PWL), adhesive removal test (ART) responsive time, sciatic nerve conduction velocity (SNCV), and intra-epidermal nerve fiber density (IENFs). Methodological quality was assessed using SYRCLE, and reporting quality using ARRIVE 2.0. Meta-analyses were conducted by Stata 18.0 and R 4.5.2.

Results

21 studies involving 451 animals were included. SYRCLE scores ranged from 6 to 7, and ARRIVE scores from 9.5 to 15.5, indicating moderate quality. Meta-analysis revealed that EA significantly increased MWT (standardized mean difference [SMD] = 4.34, 95% confidence interval [CI]: 3.34 to 5.34, I² = 78.5%) and PWL (SMD = 5.86, 95% CI: 3.97 to 7.75, I² = 78.2%) compared to model group. EA also significantly shortened ART responsive time (SMD = −3.76, 95% CI: −6.69 to −0.83, I² = 88.0%), improved SNCV (SMD = 5.56, 95% CI: 4.10 to 7.02, I² = 0%) and preserved IENFs (SMD = 3.39, 95% CI: 2.34 to 4.45, I² = 0%). Mechanistically, EA attenuated neuroinflammation, modulated ion channels, activated antioxidant pathways, and regulated neurotransmitter release.

Conclusion

Preclinical evidence demonstrates that EA effectively alleviates pain-like behaviors, improves sensory recovery, and enhances neurological function in CIPN models through multi-target mechanisms. These findings support EA as a promising intervention warranting further research.

Keywords: peripheral nervous system diseases, electroacupuncture, oxaliplatin, complementary therapies, inflammation

Introduction

In 2022, approximately 20 million new cancer cases and nearly 10 million cancer-related deaths were recorded globally.¹ While the therapeutic landscape for cancer is increasingly diverse, chemotherapy remains a key component in the management of a broad range of malignancies.² Chemotherapy acts by targeting rapidly dividing cells with cytotoxic chemicals, thereby controlling tumor progression and extending patient survival.³ Nevertheless, its clinical utility is often offset by a spectrum of adverse effects that may compromise treatment adherence, tolerance, and patient well-being.⁴ As a prevalent and dose-limiting adverse effect, chemotherapy-induced peripheral neuropathy (CIPN) is frequently linked to taxanes, platinum agents, and vinca alkaloids.⁵ CIPN typically presents as a symmetrical, length-dependent sensorimotor neuropathy, with symptoms including pain, tingling, numbness, and hypersensitivity in the distal extremities.⁶ Epidemiologically, it affects 30–85% of patients undergoing treatment, significantly impairing daily function and often necessitating dose reduction or premature cessation of potentially life-prolonging therapy.^7–9

Currently, there is a notable lack of effective pharmacological agents for preventing or treating CIPN.¹⁰ Duloxetine is the only drug recommended for painful CIPN by the American Society of Clinical Oncology (ASCO) clinical practice guideline; however, its efficacy is often limited and associated with substantial adverse effects.¹¹ Therefore, there is a clear unmet need for more effective therapeutic strategies for managing CIPN. Electroacupuncture (EA) has emerged as a promising intervention for neuropathic pain conditions. Accumulating clinical evidence suggests that EA may alleviate neuropathic pain and improve neurological function in cancer patients suffering from CIPN.^12–14 Preclinical evidence indicates that EA ameliorates CIPN through some mechanisms, particularly suppression of neuroinflammation and modulation of ion channel function.¹⁵^,¹⁶

Animal models are indispensable for investigating the pathophysiology of CIPN because they enable controlled mechanistic investigations that cannot be performed in patients. In preclinical research, animal models of CIPN induced by paclitaxel or cisplatin via clinically relevant administration routes have demonstrated high translational value.¹⁷ Importantly, clinically relevant CIPN models induced by commonly used chemotherapeutic agents closely reproduce the pathological alterations and pain-related phenotypes observed in patients, providing an essential platform for evaluating therapeutic efficacy and exploring disease mechanisms.¹⁸ Consequently, evidence generated from these models serves as a critical bridge between mechanistic discovery and subsequent clinical translation.¹⁹

Although accumulating studies have demonstrated beneficial effects of EA in CIPN,²⁰^,²¹ substantial heterogeneity has limited direct comparison across studies. Consequently, the overall efficacy of EA, the consistency of its biological mechanisms, and the potential sources of heterogeneity remain incompletely understood. A comprehensive synthesis of the available preclinical evidence is therefore needed to provide a stronger foundation for future mechanistic and translational research. This study aims to synthesize the existing preclinical evidence on EA for CIPN and to consolidate the current understanding of its potential therapeutic mechanisms.

Methods

This study was prospectively registered on PROSPERO (CRD 420261286363) and all analyses were performed in accordance with the registered protocol. The study was conducted in accordance with the updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Search Strategy

A comprehensive search was conducted across seven databases, including PubMed, Web of Science, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, and the Chinese Scientific Journal Database (VIP), from inception to June 24, 2026. The aim was to identify relevant animal studies investigating electroacupuncture for CIPN. This search had no language restrictions. Supplementary Table 1 presents the full search strategy.

Eligibility Criteria

Two independent reviewers (T-MJ and L-YH) established the following inclusion and exclusion criteria.

Inclusion Criteria

(1)
Population: Experimental studies utilizing mammalian animal models (eg, rats, mice) with explicitly established CIPN. The model must be induced by chemotherapeutic agents such as paclitaxel, cisplatin, or oxaliplatin.
(2)
Intervention: The experimental group must receive EA treatment, defined as electrical stimulation applied via needles inserted at specific acupoints. Detailed EA parameters, treatment course, and acupoint locations must be described. For studies with multiple EA intervention arms using different stimulation parameters, we selected the arm with the highest stimulation frequency for inclusion in the primary meta-analysis.
(3)
Comparison: The control group included the CIPN model group or the sham EA group.
(4)
Outcomes: The primary outcome was the mechanical withdrawal threshold (MWT), with secondary outcomes including thermal withdrawal latency (PWL), adhesive removal test (ART) responsive time, sciatic nerve conduction velocity (SNCV), and intra-epidermal nerve fibers (IENFs). For studies reporting outcome data at multiple time points, we consistently extracted data from the time point corresponding to the end of the treatment course (the final assessment after the last EA session).

Exclusion Criteria

(1)
Invalid CIPN models or models induced by non-chemotherapeutic neuropathic methods;
(2)
Using other therapies or combination therapies, such as manual acupuncture, warm needling, moxibustion or Chinese medicine;
(3)
Absence of corresponding outcome indicators;
(4)
Non-randomized designs, observational studies, reviews or unpublished reports.

Literature Screening and Data Extraction

Two independent reviewers (T-MJ and L-YH) conducted literature screening and data extraction. In case of disagreement, consensus was reached through discussion or referral to a third reviewer (X-ZQ). Two-step screening was performed: first by title/abstract, then by full-text against inclusion criteria. Using a standardized form, we extracted: (1) basic study characteristics (first author, year of publication, country); (2) animal model details (species, strain, sex, sample size, and modeling method); (3) intervention parameters (acupoints, EA waveform, electricity, frequency, duration, and treatment course); (4) control group design; (5) primary and secondary outcomes. All outcomes are presented as mean ± standard deviation. For outcome data presented in graphs, numerical values were digitized using GetData Graph Digitizer 2.26.

Risk of Bias

Two reviewers (Z-SY and X-H) independently assessed the risk of bias using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool.²² This tool assesses bias across 10 key domains specific to in vivo research. Disagreements were resolved by consultation with a third reviewer (Z-TY). The overall assessment will be presented graphically to summarize the potential biases within the selected literature.

Quality of Reporting Evidence

To evaluate the completeness of reporting in the included animal studies, two independent assessors (T-MJ and L-YH) applied the ARRIVE (Animal Research: Reporting of In Vivo Experiments) 2.0 guidelines.²³ A scoring system was implemented wherein each checklist item received a score of 1 for full adherence, 0.5 for partial adherence, or 0 for non-adherence. Disagreements were resolved by consulting a third reviewer (Z-TY).

Statistical Analysis

All statistical analyses for the meta-analysis were conducted in Stata 18.0 and R 4.5.2. As the outcomes of interest were continuous variables, the standardized mean difference (SMD) along with its 95% confidence interval (CI) was calculated as the pooled effect measure. Statistical significance was defined as a two-sided P-value < 0.05. Heterogeneity across studies was quantified using the I² statistic; a fixed-effects model was applied when I²≤50%, indicating low to moderate heterogeneity, whereas a random-effects model was adopted for higher heterogeneity (I²>50%). To address significant heterogeneity, meta-regression and subgroup analysis is utilized to identify underlying sources. Furthermore, sensitivity analysis is employed to test the robustness of the findings. To assess potential publication bias, funnel plots were visually inspected and supplemented with Egger’s test. We also employed the trim-and-fill method to evaluate the potential impact of publication bias on the study outcomes.

Results

Search Results and Study Selection

A systematic literature search was conducted across multiple databases following a predefined strategy developed by two independent reviewers (T-MJ and L-YH), yielding 2103 records. After removing 640 duplicates, 1463 articles were screened based on titles and abstracts. Excluded at this stage were 595 reviews, 79 meta-analyses, 61 case reports, 564 clinical trials, and 113 studies unrelated to the topic. Full-text retrieval was attempted for the remaining articles, of which two could not be obtained. Of the 49 full‑text articles assessed for eligibility, 24 were excluded due to the absence of EA intervention, and 4 lacked the required outcome measures. Ultimately, 21 studies met the inclusion criteria and were included in this systematic review and meta-analysis (Figure 1).

A flowchart detailing study identification, screening and inclusion process for a systematic review. The flowchart outlines the process of identifying studies via databases and registers. It begins with the identification phase, where records are sourced from various databases: Pubmed (183), Web of Science (530), Embase (316), Cochrane Library (380), CNKI (158), Wan fang (258) and VIP (278). Duplicate records removed before screening total 640, with no records marked ineligible by automation tools or removed for other reasons. Screening follows, with 1463 records screened. Exclusions include 595 reviews, 79 meta-analyses, 61 case reports, 564 clinical trials and 113 irrelevant topics, totaling 1412 exclusions. Reports sought for retrieval number 51, with 2 not retrieved. Eligibility assessment includes 49 reports, excluding 24 for using interventions other than electroacupuncture and 4 for lacking predetermined outcome indexes. Finally, 21 studies are included in the review, with 21 reports of included studies. — Flow diagram of the study.

Study Characteristics

A total of 21 studies¹⁶^,^24–43 were included for baseline characteristic analysis (Table 1). Detailed intervention characteristics and outcome assessments are provided in Supplementary Table 2 and 3. The analysis encompassed 451 animals, comprising 177 in the EA group, 178 in the model group, and 96 in the sham EA group. Regarding animal species, Sprague‑Dawley (SD) rats were the most frequently used strain, employed in 11 studies.¹⁶^,²⁷^,³²^,³³^,³⁵^,^37–42 This was followed by C57BL/6J mice, used in 9 studies,²⁴^,²⁵^,^28–31^,³⁴^,³⁶^,⁴³ and ICR mice in 1 study.²⁶ In terms of modeling methods, all studies established CIPN via intraperitoneal injection. Paclitaxel was administered in 13 studies,^24–26^,^30–33^,³⁶^,^39–43 oxaliplatin in 5 studies,¹⁶^,²⁷^,³⁵^,³⁷^,³⁸ and cisplatin in 3 studies.²⁸^,²⁹^,³⁴ With regard to EA waveforms, dense‑sparse waves were predominantly applied, reported in 6 studies.²⁵^,²⁹^,³⁰^,³⁴^,³⁶^,³⁷ Continuous waves were used in 7 studies.²⁷^,³³^,³⁵^,^40–43 The remaining 8 studies did not explicitly specify the waveform.¹⁶^,²⁴^,²⁶^,²⁸^,³¹^,³²^,³⁸^,³⁹ Regarding acupoint selection, 11 studies employed a single acupoint, all of which used Zusanli (ST36) alone.¹⁶^,²⁴^,²⁶^,²⁷^,^35–38^,^41–43 Ten studies used two acupoints, with the most common combination being Zusanli (ST36) plus Kunlun (BL60), appearing in 5 studies.²⁸^,^31–34 For outcome measures, MWT was the most frequently assessed endpoint, reported in 18 studies.²⁴^,²⁵^,²⁸^,²⁹^,^31–43 PWL was evaluated in 7 studies.²⁵^,²⁶^,³⁰^,³²^,⁴⁰^,⁴²^,⁴³ The ART was used in 3 studies.²⁸^,²⁹^,³⁴ SNCV was measured in 3 studies,²⁷^,³⁷^,³⁸ and IENFs was examined in 3 studies.²⁹^,³¹^,³⁴

Table 1.

Characteristics of the Included Studies

Study	Country	Animals (Species, Sex)	Electroacupuncture Intervention (Waveform, Electricity, Frequency, Duration) (n)	Acupoints	Treatment Course	Control Group (n)	Modeling Method	Outcome
Choi 2015²⁶	Republic of Korea	ICR mice, male	EA (2mA, 2Hz, 30min every other day) (n=11)	Zusanli (ST36)	2w	CIPN model group (n=11); Sham EA group (n=11)	Intraperitoneal injection of paclitaxel (4 mg/kg)	b
Sui 2016³⁶	USA	C57BL/6J mice, male	EA (1~1.5mA, 2Hz/100Hz, every other day, three times a week) (n=16)	Zusanli (ST36)	3w	CIPN model group (n=16); Sham EA group (n=16)	Intraperitoneal injection of paclitaxel (2 mg/kg)	a
Cui 2017²⁷	China	SD rats, male,	EA (continuous wave, 2mA, 2Hz, 30 min/d) (n=10)	Zusanli (ST36)	5d	CIPN model group (n=10); Sham EA group (n=10)	Intraperitoneal injection of oxaliplatin (6 mg/kg)	d
Li 2019³²	China	SD rats, male	EA (0.5~1.5mA, 2Hz, 30min/d) (n=5)	Zusanli (ST36), Kunlun (BL60)	7d	CIPN model group (n=5); Sham EA group (n=5)	Intraperitoneal injection of paclitaxel (2 mg/kg)	ab
Li-YY 2019³³	China	SD rats, male	EA (continuous wave, 0.5~1.5mA, 2Hz, 30 min/d) (n=7)	Zusanli (ST36), Kunlun (BL60)	12d	CIPN model group (n=7); Sham EA group (n=7)	Intraperitoneal injection of paclitaxel (2 mg/kg)	a
Zhao 2019⁴⁰	China	SD rats, male	EA (Continuous wave, 2mA, 2Hz, 20min/d) (n=8)	Neiguan (PC6), Jianshi (PC5)	5d	CIPN model group (n=9)	Intraperitoneal injection of paclitaxel (1 mg/kg)	ab
Shi 2020³⁵	China	SD rats, male	EA (continuous wave, 1mA, 2Hz, 30 min every other day) (n=10)	Zusanli (ST36)	2w	CIPN model group (n=10)	Intraperitoneal injection of oxaliplatin (2 mg/kg)	a
Zhao 2020⁴¹	China	SD rats, male	EA (Continuous wave, 1mA, 10Hz, 30 min every other day) (n=7)	Zusanli (ST36)	2w	CIPN model group (n=8); Sham EA group (n=7)	Intraperitoneal injection of paclitaxel (2 mg/kg)	a
Ma 2022³⁴	China	C57BL/6J mice, male	EA (Dense-sparse wave, 2mA, 2Hz/100Hz, 15min/d) (n=6)	Zusanli (ST36), Kunlun (BL60)	3w	CIPN model group (n=6); Sham EA group (n=6)	Intraperitoneal injection of cisplatin (2.3 mg/kg)	ace
Wang 2022¹⁶	China	SD rats, male	EA (1mA, 2Hz, 30min/d) (n=10)	Zusanli (ST36)	2w	CIPN model group (n=10)	Intraperitoneal injection of oxaliplatin (2 mg/kg)	a
Xiong 2023³⁷	China	SD rats, male	EA (Dense-sparse wave, 2mA,2Hz/15Hz, 20 min/d) (n=5)	Zusanli (ST36)	2w	CIPN model group (n=5)	Intraperitoneal injection of oxaliplatin (2 mg/kg)	ad
Ye 2023³⁸	China	SD rats, male	EA (3mA, 5Hz, 10 min/d) (n=5)	Zusanli (ST36)	2w	CIPN model group (n=5)	Intraperitoneal injection of oxaliplatin (2 mg/kg)	ad
Yoon 2023³⁹	Republic of Korea	SD rats, male	EA (4mA, 50Hz, 6min every other day) (n=7)	Zhongwan (CV12), Zusanli (ST36)	15d	CIPN model group (n=7)	Intraperitoneal injection of paclitaxel (2 mg/kg)	a
Chen 2025²⁴	China	C57BL/6J mice, male and female	EA (0.5mA, 2Hz, 20min/d) (n=16)	Zusanli (ST36)	4d	CIPN model group (n=16)	Intraperitoneal injection of paclitaxel (2 mg/kg)	a
Chen-XM 2025²⁵	China	C57BL/6J mice, male	EA (Dense-sparse wave, 1mA, 2Hz/100Hz, 20 min every other day) (n=8)	Lower4, Lower5	2w	CIPN model group (n=8)	Intraperitoneal injection of paclitaxel (2 mg/kg)	ab
Fu 2025²⁸	China	C57BL/6J mice, male	EA (1~2mA, 10Hz, 30min/d) (n=9)	Zusanli (ST36), Kunlun (BL60)	3w	CIPN model group (n=8); Sham EA group (n=9)	Intraperitoneal injection of cisplatin (2.3 mg/kg)	ac
Lan 2025³⁰	China	C57BL/6J mice, male	EA (Dense-sparse wave, 1mA, 2Hz/100Hz, 30 min every other day) (n=12)	Lower4, Lower5	2w	CIPN model group (n=12)	Intraperitoneal injection of paclitaxel (2 mg/kg)	b
Li 2025³¹	China	C57BL/6J mice, male	EA (0.5mA, 2Hz, 30min/d) (n=5)	Zusanli (ST36), Kunlun (BL60)	7d	CIPN model group (n=5); Sham EA group (n=5)	Intraperitoneal injection of paclitaxel (2 mg/kg)	ae
Jiang 2026²⁹	China	C57BL/6J mice, male	EA (Dense-sparse wave, 1~2mA, 2Hz/100Hz, 30min/d) (n=8)	Zusanli (ST36), Shenmen (HT7)	2w	CIPN model group (n=8); Sham EA group (n=8)	Intraperitoneal injection of cisplatin (2.3 mg/kg)	ace
Wang 2026⁴²	China	SD rats, male	EA (Continuous wave, 1 mA, 10 Hz, 30 min every other day) (n=6)	Zusanli (ST36)	9d	CIPN model group (n=6); Sham EA group (n=6)	Intraperitoneal injection of paclitaxel (2 mg/kg)	ab
Zhou 2026⁴³	China	C57BL/6J mice, male	EA (Continuous wave, 1 mA, 10 Hz, 30 min every other day) (n=6)	Zusanli (ST36)	15d	CIPN model group (n=6); Sham EA group (n=6)	Intraperitoneal injection of paclitaxel (2 mg/kg)	ab

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Abbreviations: ^aMWT, mechanical paw withdrawal threshold; ^bPWL, thermal withdrawal latency; ^cART, adhesive removal test responsive time; ^dSNCV, sciatic nerve conduction velocity; ^eIENFs, intraepidermal nerve fibers.

Risk of Bias

The results of risk of bias are presented in Figure 2 and Supplementary Table 4. Regarding randomization, 8 studies reported using a random number table or software‑generated randomization, 12 studies mentioned randomization without specifying the method, and 1 study did not mention randomization methods. All studies reported baseline comparability among groups; only one study failed to report details on animal housing conditions, and none of the studies reported allocation concealment. Due to electroacupuncture intervention, blinding of investigators was not feasible in any of the studies. All 21 included studies incorporated all animals in the outcome analysis. Three studies explicitly reported blinding of outcome assessment, whereas the remaining 18 studies did not specify whether blinding was applied to outcome assessors. All studies reported complete outcome data. No evidence of selective outcome reporting was identified, and no other obvious sources of high risk of bias were detected. The risk of bias scores ranged from 6 to 7, with a mean ± SD of 6.45 ± 0.51.

Quality Assessment

Reporting quality was evaluated according to the ARRIVE 2.0 checklist. The quality was consistently poor for item 5 (Blinding), item 19 (Protocol registration), and item 20 (Data access). In addition, incomplete reporting was frequently observed for item 14 (Ethical statement), item 16 (Animal care and monitoring), and item 18 (Generalizability/translation). The detailed assessment is presented in Figure 3 and Supplementary Table 5. Regarding study design, although all studies clearly described the experimental groups and unit of analysis, randomization methods were only partially reported, and no study implemented or described blinding procedures. For sample size, all studies specified the number of animals per group, yet none provided a priori sample size calculation or justification. Inclusion and exclusion criteria were either omitted or only partially described across all studies. Outcome measures were generally well defined; however, the primary outcome was rarely explicitly stated. Statistical methods were partially reported, with most studies lacking descriptions of assumption verification or data transformation. The quality scores ranged from 9.5 to 15.5, with a mean ± SD of 11.38 ± 1.47.

A stacked horizontal bar graph showing reporting quality results across items 1 to 21. A horizontal bar graph with 21 bars labeled Item 1 to Item 21. X-axis: percent (0-100%). Y-axis: Items. Legend: Yes, Partly yes, Non-conformance. Item breakdown: 1: Partly yes 36%, Yes 64%. 2: Partly yes 95%, Yes 5%. 3: Partly yes 100%. 4: Non-conformance 37%, Partly yes 63%. 5: Non-conformance 51%, Partly yes 49%. 6: Partly yes 91%, Yes 9%. 7: Partly yes 100%. 8: Partly yes 86%, Yes 14%. 9: Partly yes 76%, Yes 24%. 10: Partly yes 66%, Yes 34%. 11: Partly yes 19%, Yes 81%. 12: Partly yes 41%, Yes 59%. 13: Partly yes 19%, Yes 81%. 14: Non-conformance 24%, Partly yes 34%, Yes 42%. 15: Non-conformance 14%, Partly yes 81%, Yes 5%. 16: Partly yes 100%. 17: Partly yes 91%, Yes 9%. 18: Non-conformance 37%, Partly yes 49%, Yes 14%. 19: Non-conformance 91%, Partly yes 9%. 20: Non-conformance 51%, Partly yes 40%, Yes 9%. 21: Non-conformance 14%, Partly yes 31%, Yes 55%. — Reporting quality for included studies.

Results of Meta-Analysis

MWT

A total of 18 studies reported MWT as an outcome measure, all comparing EA with the model group, of which 10 also included a sham EA group. Meta‑analysis demonstrated that MWT were significantly higher in the EA group than in the model group (SMD = 4.34, 95% CI: 3.34 to 5.34; I² = 78.5%) (Figure 4A). Similarly, MWT were significantly higher in the EA group than in the sham EA group (SMD = 4.73, 95% CI: 2.97 to 6.49; I² = 88.5%) (Figure 4B).

Three forest plots comparing standardized mean difference for mechanical and thermal withdrawal outcomes. The text describes three forest plots (A, B, C) with Study ID, SMD (95% CI) and percent Weight. Each plot has a horizontal axis labeled SMD (95% CI) with a vertical reference line at 0. Study results are shown with square markers and horizontal confidence interval lines, while a diamond marker indicates the overall effect. In Image A, studies like Ye (2023) and Chen-XM (2025) show varying SMDs, with an overall effect of 4.34 (3.34, 5.34) and I-squared of 78.5%. Image B includes studies such as Sui (2016) and Zhu (2026), with an overall effect of 4.73 (2.97, 6.49) and I-squared of 88.5%. Image C features studies like Chen-XM (2025) and Wang (2026), with an overall effect of 5.86 (3.97, 7.75) and I-squared of 78.2%. All plots use random effects analysis and the overall diamonds are on the positive side of 0, indicating a positive effect across studies. — Forest plots of mechanical withdrawal threshold (MWT) and thermal withdrawal latency (PWL). (A) MWT in EA group compared to model group. (B) MWT in EA group compared to sham EA group. (C) PWL in EA group compared to model group.

To further explore potential sources of the substantial heterogeneity in MWT, we performed meta-regression analyses with covariates including animal species, number of acupoints, chemotherapeutic agent, treatment duration, cumulative dose, and EA frequency. The results revealed that none of these factors significantly explained the heterogeneity: animal species (P = 0.538), number of acupoints (P = 0.550), chemotherapeutic agent (P = 0.523), treatment duration (P = 0.391), cumulative dose (P = 0.164) and EA frequency (P = 0.209) (Supplementary Table 6). Subsequently, subgroup analyses were conducted based on these six variables to further investigate their potential impact. In the stratification by treatment duration, studies with ≤1 week showed low heterogeneity (I² = 0%, P > 0.05), whereas those with >2 weeks exhibited moderate heterogeneity (I² = 72.4%, P = 0.006), and the 1–2 weeks subgroup showed substantial heterogeneity (I² = 83.0%, P < 0.001). The pooled effect sizes differed significantly among the three subgroups (P < 0.001), suggesting treatment duration as a moderating factor, although it was not significant in the meta-regression analysis. For animal species, a significant between‑group difference was detected between SD rats and C57BL/6J mice (P = 0.010). Subgroup analysis by chemotherapeutic agent (oxaliplatin, paclitaxel, cisplatin) revealed no significant between‑group difference (P = 0.679). Similarly, number of acupoints (single vs dual) yielded no significant difference between subgroups (P = 0.738). Subgroup analysis by cumulative dose revealed no significant between-group difference (P = 0.089). In contrast, subgroup analysis by EA frequency showed a significant between-group difference (P < 0.001), with studies using 2Hz and 2/100Hz demonstrating comparatively larger effect sizes, suggesting that stimulation frequency may be a potential moderating factor. These findings indicate that chemotherapeutic agent, number of acupoints, and cumulative dose do not critically influence EA efficacy, whereas EA frequency may warrant further investigation (Supplementary Figure 1).

PWL

7 studies reported PWL as an outcome measure, all comparing the EA group with the model group. Meta-analysis showed that PWL were significantly higher in the EA group than in the model group (SMD = 5.86, 95% CI: 3.97 to 7.75, I² = 78.2%) (Figure 4C).

ART Responsive Time

3 studies reported ART responsive time as an outcome measure, all comparing the EA group with the model group and sham EA group. Meta-analysis showed that ART responsive time was significantly shorter in the EA group than in the model group (SMD = −3.76, 95% CI: −6.69 to −0.83; I² = 88.0%) (Figure 5A). Similarly, EA significantly reduced ART responsive time compared to the sham EA group (SMD = −1.42, 95% CI: −2.10 to −0.75; I²= 0%) (Figure 5B).

Two forest plots of adhesive removal test responsive time showing negative pooled effects across studies. Image A shows a forest plot with studies Ma 2022, Jiang 2026, Fu 2025 and an Overall row. The x-axis ranges from -12.5 to 12.5, with a vertical line at 0. Each study is represented by a square and a horizontal confidence interval line. Right-side columns display SMD (95% CI) and Weight. Values: Ma 2022, -1.33 (-2.60, -0.05), weight 37.40; Jiang 2026, -9.05 (-12.54, -5.56), weight 25.59; Fu 2025, -2.56 (-3.92, -1.20), weight 37.01. Overall diamond: -3.76 (-6.69, -0.83), weight 100.00. Text reads Overall (I-squared = 88.0%, p = 0.000). Image B shows a similar plot with the same studies and Overall row. The x-axis ranges from -3.68 to 3.68, with a vertical line at 0. Right-side columns display SMD (95% CI) and Weight. Values: Ma 2022, -2.20 (-3.68, -0.71), weight 20.42; Jiang 2026, -1.15 (-2.22, -0.08), weight 39.49; Fu 2025, -1.30 (-2.36, -0.24), weight 40.08. Overall diamond: -1.42 (-2.10, -0.75), weight 100.00. Text reads Overall (I-squared = 0.0%, p = 0.511). — Forest plots of adhesive removal test (ART) responsive time. (A) ART responsive time in EA group compared to model group. (B) ART responsive time in EA group compared to sham EA group.

SNCV

Three studies reported SNCV as an outcome measure, all comparing the EA group with the model group. Meta-analysis showed that SNCV were significantly higher in the EA group than in the model group (SMD = 5.56, 95% CI: 4.10 to 7.02, I² = 0%) (Figure 6A).

Three forest plots comparing standardized mean difference across studies, with pooled effects favoring treatment. Image A shows a forest plot of standardized mean differences. Studies include Cui 2017, Ye 2023 and Xiong 2023 with mean differences of 5.53 (CI: 3.53-7.54, weight 52.80), 5.31 (CI: 2.43-8.19, weight 25.68) and 5.60 (CI: 2.76-8.60, weight 21.53) respectively. Overall mean difference is 5.56 (CI: 4.10-7.02, weight 100.00). Image B features studies Ma 2022, Li 2019 and Jiang 2019 with mean differences of 4.44 (CI: 3.44-5.13, weight 25.29), 3.97 (CI: 3.16-4.80, weight 22.01) and 2.99 (CI: 1.54-4.25, weight 52.70). Overall mean difference is 3.39 (CI: 2.34-4.45, weight 100.00). Image C includes the same studies with mean differences of -0.19 (CI: -0.21 to -0.17, weight 39.99), -0.03 (CI: -0.25 to 0.19, weight 25.84) and -0.11 (CI: -0.14 to -0.08, weight 34.17). Overall mean difference is -0.12 (CI: -0.17 to -0.07, weight 100.00). — Forest plots of sciatic nerve conduction velocity (SNCV) and intraepidermal nerve fiber density (IENFs). (A) SNCV in EA group compared to model group. (B) IENFs in EA group compared to model group. (C) IENFs in EA group compared to sham EA group.

IENFs

3 studies reported IENFs as an outcome measure, all comparing the EA group with the model group and sham EA group. In the meta‑analysis, the EA group showed a significantly higher IENFs compared with the model group (SMD = 3.39, 95% CI: 2.34 to 4.45, I² = 0%) (Figure 6B). However, no statistically significant difference was observed between the EA group and the sham EA group (SMD = 1.42, 95% CI: −7.91, 10.74; I² = 94.7%) (Figure 6C).

Publication Bias

To assess potential publication bias, a funnel plot was generated and Egger’s test was performed. The funnel plot exhibited asymmetry, and Egger’s test revealed significant publication bias for MWT (P < 0.05), suggesting the presence of publication bias (Figure 7 and Supplementary Table 7).

Two scatter plots showing standardized mean difference versus its standard error for EA group comparisons. — Funnel plot of mechanical withdrawal threshold. (A) EA group compared to model group. (B) EA group compared to sham EA group.

Sensitivity Analysis

We conducted a leave-one-out sensitivity analysis to assess the robustness of the pooled results. The findings indicated that all outcomes remained stable (P < 0.05) (Supplementary Figure 2). To assess the potential impact of publication bias on MWT, we applied the trim-and-fill method. For MWT comparing EA with the model group, the original unadjusted SMD was 3.35 (95% CI: 2.94 to 3.76) under the fixed-effects model and 4.34 (95% CI: 3.34 to 5.34) under the random-effects model. After imputing six studies, the adjusted SMD was 2.82 (95% CI: 2.28 to 3.36) under the fixed-effects model and 2.98 (95% CI: 2.01 to 3.95) under the random-effects model. For MWT comparing EA with the sham EA group, the original unadjusted SMD was 2.14 (95% CI: 1.58 to 2.70) under the fixed-effects model and 4.73 (95% CI: 2.97 to 6.49) under the random-effects model. After imputing two studies, the adjusted SMD was 2.54 (95% CI: 2.03 to 3.05) under the fixed-effects model and 3.77 (95% CI: 2.54 to 5.00) under the random-effects model. Although the adjusted effect sizes were attenuated compared to the original estimates, the results remained statistically significant (P < 0.001), indicating that the primary conclusion of EA efficacy is robust despite the presence of publication bias (Supplementary Table 8).

Mechanisms of EA Treatment in CIPN Animal Models

Table 2 and Figure 8 summarize the proposed mechanisms.

Table 2.

Proposed Mechanisms of Studies Included

Study	Anatomical Site	Upstream Regulation	Core Targets or Signaling Events	Downstream or Associated Effects
Neuroinflammatory regulation
Zhao 2020⁴¹	Spinal cord; serum	Reduced TLR4 expression	Reduced NF-κB p65 expression	Reduced microglial and astrocytic activation and IL-1β and TNF-α levels; reduced mechanical allodynia.
Wang 2026⁴²	Spinal cord	Reduced TLR4 expression	Suppressed MyD88/TRIF-associated signaling	Altered neuronal and glial activation markers and inflammatory cytokine profiles; reduced mechanical and thermal hypersensitivity.
Zhou 2026⁴³	DRG; spinal cord; plantar tissue	Reduced TLR4 and P2X7 expression in DRG and spinal cord	Reduced NLRP3 and NF-κB expression	Reduced IL-1β and IL-18; reduced plantar substance P, CGRP and p75 expression; reduced mechanical and thermal hypersensitivity.
Chen-XM 2025²⁵	Spinal dorsal horn	Increased α7nAChR expression	Reduced JAK2 and STAT3 phosphorylation	Reduced microglial activation and TNF-α, IL-1β and IL-6 mRNA; reduced mechanical and thermal hypersensitivity. Receptor involvement supported by antagonism.
Fu 2025²⁸	Spinal dorsal horn	Increased Igf1 mRNA and neuronal IGF1R phosphorylation	Increased neuronal GRK2 expression	Reduced microglial activation and neuroinflammation; improved mechanical allodynia and sensory deficits. Neuronal IGF1R involvement supported by knockdown.
Ma 2022³⁴	Spinal dorsal horn	Upstream regulator of GRK2 not established	Increased neuronal GRK2; reduced TREM2/DAP12 expression	Reduced proinflammatory microglial markers and inflammatory mediators; improved mechanical allodynia, sensory deficits and IENF loss. GRK2 involvement supported by neuronal manipulation.
Li 2025³¹	DRG; sciatic nerve; skin	Reduced CCL2 production by DRG neurons	Reduced CCR2-mediated macrophage recruitment	Reduced proinflammatory macrophage infiltration, sensory neuron injury and IENF loss; reduced mechanical and cold hypersensitivity. Supported by CCR2 blockade and CCL2 administration.
Ye 2023³⁸	Spinal cord; sciatic nerve	Not established	Reduced spinal GFAP expression, an astrocytic marker	Improved spinal histology and SNCV; increased mechanical withdrawal threshold. Marker changes do not establish a causal pathway.
Sui 2016³⁶	Serum	Not established	No specific signaling target established	Reduced serum IL-1α and mechanical hypersensitivity. Reductions in TNF-α and IL-1β were not statistically significant.
Ion channel and calcium signaling
Li 2019³²	DRG neurons; spinal cord	Reduced TLR4/MyD88 signaling	Reduced TRPV1 expression and channel activity	Reduced spinal glial activation and mechanical and thermal hypersensitivity. TRPV1 involvement supported by antagonist and agonist experiments.
Li-YY 2019³³	DRG	Not established	Reduced TRPV1 expression	Increased mechanical withdrawal threshold; association between TRPV1 expression and behavioral improvement.
Jiang 2026²⁹	PVT; skin	Reduced TRPC6 activation and Ca²⁺ influx	Reduced PKC phosphorylation	Reduced PVT glutamatergic neuronal activation and glutamate release; improved pain, cutaneous sensory deficits and anxiety-like behavior; preserved IENFs and Merkel cells.
Antioxidant signaling and associated channel regulation
Zhao 2019⁴⁰	DRG	Restored Nrf2 expression	Increased NQO1 and SOD expression; reduced NOX4 expression	Reduced oxidative stress products, including 8-iso-PGF2α and 8-OHdG; reduced mechanical and thermal hypersensitivity.
Wang 2022¹⁶	DRG; peripheral microcirculation	Increased Nrf2 expression	Increased HO-1 expression; concomitantly reduced TRPV1, TRPA1 and TRPM8 expression	Improved DRG ultrastructure and microcirculatory blood flow; reduced mechanical and cold allodynia.
Receptor-mediated and supraspinal pain modulation
Choi 2015²⁶	Spinal dorsal horn	Spinal opioid receptor, α2-adrenoceptor and β-adrenoceptor involvement	Reduced phosphorylation of the NMDA receptor NR2B subunit	Reduced mechanical allodynia and thermal hyperalgesia. Receptor antagonists attenuated analgesia and prevented the reduction in NR2B phosphorylation.
Lan 2025³⁰	Spinal dorsal horn	Increased 5-HT1AR expression	Reduced VGluT2 expression and CaMKII phosphorylation	Reduced glutamate content and thermal hypersensitivity. Receptor involvement supported by 5-HT1AR antagonism.
Chen 2025²⁴	RVM; spinal cord	Modulation of RVM astrocyte function	Reduced astrocytic Ca²⁺ signaling	Reduced neuronal activation in the RVM and spinal cord and mechanical allodynia. RVM astrocyte involvement supported by chemogenetic activation and calcium-suppressing manipulations.
Peripheral neurotrophic and structural changes
Shi 2020³⁵	Sciatic nerve	Not established	Reduced TRPA1 expression and increased NGF expression, observed in parallel	Improved myelin morphology; reduced mechanical and cold hypersensitivity. A regulatory relationship between TRPA1 and NGF was not established.
Xiong 2023³⁷	Sciatic nerve; DRG	Not established	Increased sciatic nerve NGF expression in the EA-only group	Improved SNCV and DRG morphology; increased mechanical withdrawal threshold. NGF changes were associated with these improvements.
Exploratory molecular findings and functional outcomes
Yoon 2023³⁹	Spinal tissue	Not established for EA alone	EA alone reduced c-Fos, NeuN, synapsin I and MAP2 protein levels	Improved mechanical withdrawal responses. These findings do not establish nerve regeneration.
Cui 2017²⁷	Sciatic nerve; behavioral testing	Not investigated	No molecular target investigated	Reduced mechanical hypersensitivity and increased SNCV.

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Abbreviations: 5-HT1AR, 5-hydroxytryptamine 1A receptor; 8-iso-PGF2α, 8-isoprostaglandin F2α; 8-OHdG, 8-hydroxy-2′-deoxyguanosine; α7nAChR, α7 nicotinic acetylcholine receptor; ARE, antioxidant response element; CaMKII, Ca²⁺/calmodulin-dependent protein kinase II; CCL2, C-C motif chemokine ligand 2; CCR2, C-C chemokine receptor 2; CGRP, calcitonin gene-related peptide; CIPN, chemotherapy-induced peripheral neuropathy; DAP12, DNAX-activating protein of 12 kDa; DRG, dorsal root ganglion; EA, electroacupuncture; GFAP, glial fibrillary acidic protein; GRK2, G protein-coupled receptor kinase 2; HO-1, heme oxygenase-1; IENF, intraepidermal nerve fiber; IGF1, insulin-like growth factor 1; IGF1R, insulin-like growth factor 1 receptor; IL, interleukin; JAK2, Janus kinase 2; MAP2, microtubule-associated protein 2; MyD88, myeloid differentiation primary response 88; NeuN, neuronal nuclei; NF-κB, nuclear factor kappa B; NGF, nerve growth factor; NLRP3, NLR family pyrin domain containing 3; NMDA, N-methyl-D-aspartate; NOX4, NADPH oxidase 4; NQO1, NAD(P)H quinone dehydrogenase 1; NR2B, NMDA receptor subunit 2B; Nrf2, nuclear factor erythroid 2-related factor 2; p75, p75 neurotrophin receptor; P2X7, P2X purinoceptor 7; PKC, protein kinase C; PVT, paraventricular thalamic nucleus; RVM, rostral ventromedial medulla; SNCV, sciatic nerve conduction velocity; SOD, superoxide dismutase; STAT3, signal transducer and activator of transcription 3; TLR4, Toll-like receptor 4; TNF, tumor necrosis factor; TREM2, triggering receptor expressed on myeloid cells 2; TRIF, TIR domain-containing adaptor-inducing interferon-β; TRPA1, transient receptor potential ankyrin 1; TRPC6, transient receptor potential canonical 6; TRPM8, transient receptor potential melastatin 8; TRPV1, transient receptor potential vanilloid 1; VGluT2, vesicular glutamate transporter 2.

Diagram of electroacupuncture effects on signaling pathways in chemotherapy-induced peripheral neuropathy. The diagram illustrates the potential mechanisms of electroacupuncture therapy in treating chemotherapy-induced peripheral neuropathy. It shows a sequence starting with electroacupuncture therapy affecting alpha7 nicotinic acetylcholine receptor, leading to modulation of various signaling pathways. Key components include TLR4, cytokines receptor and TREM2/DAP12 on the cell membrane. Downstream signaling involves p38 MAPK, JAK2, MyD88, IFN, JAK1, P13K, AKT, mTOR, GSK-3beta, TFEB, LAMP1 and SYK. The pathway influences the NLRP3 inflammasome and caspase activation, affecting pro-inflammatory cytokines like IL-1beta, TNF-alpha and IL-6, while increasing anti-inflammatory cytokines IL-4 and IL-10. The nucleus shows NF-kappaB activation through p50 and p65, indicating transcriptional regulation. The diagram highlights the complex interactions and regulatory effects of electroacupuncture on neuroinflammatory and signaling pathways. — Potential mechanisms of electroacupuncture in treating chemotherapy-induced peripheral neuropathy. ↑ represents upregulation or increase; ↓ represents downregulation or decrease.

Discussion

Research Background and Significance

Chemotherapy, a cornerstone of antitumor therapy, frequently induces CIPN, a dose-limiting toxicity for which pharmacological options are limited and often accompanied by adverse effects. EA is effective in alleviating CIPN symptoms, yet its mechanisms remain unclear. Animal models are critical for mechanistic research, but heterogeneous experimental designs across studies hinder definitive conclusions. To address this gap, we conducted a systematic review and meta-analysis of preclinical EA studies to evaluate its efficacy, explore underlying mechanisms, and reduce unnecessary animal experimentation.

Summary of Findings

Our meta-analysis demonstrated that EA intervention significantly alleviated pain-like behaviors and improved neurological function in CIPN animal models. Specifically, compared with the model group, EA treatment markedly increased MWT and PWL, indicating a robust analgesic effect. Furthermore, EA significantly improved nerve function, as evidenced by increased SNCV and a higher density of IENFs relative to model controls. In ART, EA also significantly reduced removal time compared to the model group, suggesting an improvement in sensory recovery. When compared with the sham EA control group, EA demonstrated a significant increase in MWT and a significant reduction in ART responsive time. However, no statistically significant differences were observed between EA and sham EA for IENFs density, highlighting the need for more rigorous sham controls in future research to rule out potential placebo effects. Collectively, these findings provide preclinical evidence that EA exerts therapeutic effects in CIPN by ameliorating mechanical and thermal hypersensitivity, promoting nerve regeneration, and improving functional outcomes.

The substantial heterogeneity observed in MWT may be primarily attributed to variations in treatment duration, as evidenced by the significant between‑subgroup difference in the subgroup analysis. The lack of statistical significance in meta‑regression might reflect limited statistical power or a non‑linear relationship between treatment duration and analgesic effect. Notably, the pronounced heterogeneity within the 1–2 weeks subgroup suggests that this period may represent a critical window during which EA efficacy is particularly sensitive to other experimental variables, such as chemotherapy dosage or timing of behavioral assessments. The significant difference observed between SD rats and C57BL/6J mice may be attributed to species‑related variations in nociceptive signaling pathways, drug metabolism, or neuroanatomical organization. In addition, EA frequency emerged as a potential moderating factor in the subgroup analysis, although this finding was not confirmed by meta-regression; this discrepancy may reflect limited statistical power and the uneven distribution of studies across frequency categories, and therefore requires confirmation in future studies adopting standardized stimulation protocols. These methodological discrepancies, although often underreported, could contribute to variability in pain threshold measurements and thereby influence the pooled effect estimates.⁴⁴ These methodological constraints warrant caution in interpretation and underscore the urgent need for preregistration of animal studies to mitigate publication bias.

The ART is a functional test that assesses sensorimotor integration by measuring the time required to detect and remove an adhesive stimulus from the paw.⁴⁵ In CIPN research, ART has been proposed as a measure of sensory recovery, but its validation status in animal models remains limited compared to more established indicators such as IENFs and SNCV. The interpretation of ART as a measure of clinical sensory recovery requires caution, as the test reflects a combination of tactile sensitivity, motor coordination, and attention. In this study, EA significantly reduced ART responsive time, suggesting improved sensorimotor function. However, further studies are needed to establish the correlation between ART performance in animal models and clinical outcomes in patients with CIPN.

Methodological and Reporting Interpretations

Methodological quality assessed by the SYRCLE tool indicated that the included studies achieved moderate overall quality, with scores ranging from 6 to 7. Most studies reported adequate baseline comparability and complete outcome data. Randomization was mentioned in the majority of studies, though details regarding sequence generation were not always fully described. However, allocation concealment was not reported in any of the included studies, representing a methodological limitation that may increase the risk of selection bias. Blinding of researchers was inherently impractical; however, three studies explicitly reported blinding of outcome assessors. These methodological characteristics are consistent with the current state of the field and highlight opportunities for further refinement in experimental design and reporting transparency in future animal studies.⁴⁶

Reporting quality assessed by the ARRIVE guidelines revealed that the included studies achieved moderate completeness, with scores ranging from 9.5 to 15.5. Most studies clearly described experimental groups, outcome measures, and animal characteristics. However, several items were less frequently reported, including a priori sample size calculation, detailed randomization methods, allocation concealment, and explicit inclusion criteria. Descriptions of animal welfare conditions and ethical approval were also often incomplete. None of the studies reported protocol pre-registration. These reporting patterns are consistent with the current state of preclinical acupuncture research and underscore the importance of adhering to the ARRIVE guidelines to enhance transparency and reproducibility in future animal studies.⁴⁷

The Potential Mechanism

The pathophysiology of CIPN is complex, involving structural and functional alterations at both the tissue and cellular levels. These changes broadly involve four interrelated mechanisms: neuroinflammation, ion channel dysfunction, oxidative stress, and neurotransmitter/receptor regulation. Regarding neuroinflammation, EA attenuates neuroinflammatory responses in the spinal cord and DRG by inhibiting glial cell activation, suppressing inflammatory signaling, reducing macrophage infiltration, and decreasing pro-inflammatory cytokines such as TNF-α and IL-1β.³⁴^,⁴¹ At the level of ion channel modulation, EA attenuates mechanical and thermal hypersensitivity by suppressing astrocytic calcium signaling and neuronal activation in the RVM,²⁴ and by downregulating TRPV1 overexpression while upregulating NGF in the DRG.³²

In terms of oxidative stress and antioxidant pathways, EA enhanced antioxidant signaling, increased antioxidant enzyme levels, and inhibited oxidative stress, while concurrently downregulating pro‑inflammatory cytokine expression, thereby alleviating pain hypersensitivity in CIPN models.⁴⁰

With respect to neurotransmitter and receptor regulation, EA exerted analgesic effects through inhibition of CaMKII in the spinal cord, an effect associated with activation of the 5-HT1AR.³⁰ Opioid receptors and adrenoceptors also mediate EA’s analgesic effects, as confirmed by antagonist studies.²⁶^,⁴⁸ In summary, the therapeutic effect of EA in CIPN reflects a holistic rebalancing of a complex network rather than modulation of a single pathway. Identifying the primary targets remains a key challenge for future research. Furthermore, heterogeneity in acupuncture protocols and stimulation parameters across studies may influence the underlying mechanisms.⁴⁹

Implications for Further Research

First, the heterogeneity observed across studies highlights the importance of standardizing key experimental parameters, including chemotherapy regimens, animal characteristics, and assessment protocols, to enhance comparability and facilitate meta-analysis. Future studies should also consider drug-specific subgroup analyses to determine whether EA efficacy varies across different chemotherapeutic agents. Second, multimodal assessment combining electrophysiology, behavior, and morphology should be encouraged to capture the complex phenotypic features of CIPN, such as IENFs, nerve conduction tests for sensory fibers, and histological assessment of the sciatic nerve.⁵⁰ Third, standardization of key experimental parameters, including animal strain, sex, age, drug administration protocols, and testing schedules, is needed to enhance cross-study comparability. Inclusion of both sexes will improve generalizability. Fourth, methodological quality requires attention. Future studies should adhere to ARRIVE2.0 and SYRCLE guidelines, particularly regarding randomization, allocation concealment, and blinding of outcome assessment. Fifth, although the trim and fill analysis suggested that the overall effect estimate remained statistically significant after adjusting for potential missing studies, the presence of publication bias indicates that studies with positive findings may be overrepresented. Therefore, the results should be interpreted with caution, and the possibility that the true effect size may be smaller than estimated cannot be excluded. Finally, EA parameters such as acupoint selection and stimulation protocols vary considerably across studies, limiting external validity. Establishing consensus on optimal intervention parameters would facilitate reproducibility and clinical translation.⁵¹

Limitations

Several limitations of this study should be acknowledged: (1) Significant publication bias was detected, suggesting that studies with positive findings may be overrepresented; (2) Substantial heterogeneity was observed across the included studies. Although meta-regression and subgroup analyses were performed using six covariates, a considerable proportion of the heterogeneity remained unexplained, which may stem from unmeasured methodological differences across laboratories, such as variations in testing devices, operator handling, and outcome assessment protocols; (3) The methodological quality of the included studies was moderate, with incomplete reporting of randomization methods, allocation concealment, and blinding of outcome assessment, potentially introducing selection and detection bias; (4) The number of studies available for secondary outcomes was relatively small, limiting the power of subgroup analyses, particularly for the analyses of cumulative dose and EA frequency, in which several subgroups contained only one or two studies; (5) Although some studies included sham EA controls, the adequacy of blinding implementation and potential placebo effects remain unclear; therefore, the comparative findings should be interpreted with caution.

Conclusion

These findings support EA as a promising therapeutic strategy for chemotherapy-induced peripheral neuropathy. Nevertheless, the current evidence is derived exclusively from animal studies with substantial methodological heterogeneity and significant publication bias, warranting cautious interpretation. Therefore, well-designed clinical studies are warranted to validate the efficacy, safety, and translational applicability of electroacupuncture in patients with CIPN.

Funding Statement

This work was supported by Nanjing Health Science and Technology Development Project (No. ZKX24044), and Jiangsu Province Graduate Research and Practice Innovation Program (No. SJCX25_1051).

Data Sharing Statement

All data analyzed in this study were extracted from previously published studies. The datasets and analysis code supporting the conclusions of this article are available from the corresponding author upon reasonable request.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflicts of interest.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

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PERMALINK

Efficacy and Proposed Mechanisms of Electroacupuncture in Animal Models of Chemotherapy-Induced Peripheral Neuropathy: A Systematic Review and Meta-Analysis

Mingjie Tang

Hang Xu

Shiyi Zheng

Yinghong Li

Tianyi Zhu

Zhongqi Xie

Zhaoming Chen

Abstract

Background

Methods

Results

Conclusion

Introduction

Methods

Search Strategy

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Literature Screening and Data Extraction

Risk of Bias

Quality of Reporting Evidence

Statistical Analysis

Results

Search Results and Study Selection

Figure 1.

Study Characteristics

Table 1.

Risk of Bias

Figure 2.

Quality Assessment

Figure 3.

Results of Meta-Analysis

MWT

Figure 4.

PWL

ART Responsive Time

Figure 5.

SNCV

Figure 6.

IENFs

Publication Bias

Figure 7.

Sensitivity Analysis

Mechanisms of EA Treatment in CIPN Animal Models

Table 2.

Figure 8.

Discussion

Research Background and Significance

Summary of Findings

Methodological and Reporting Interpretations

The Potential Mechanism

Implications for Further Research

Limitations

Conclusion

Funding Statement

Data Sharing Statement

Author Contributions

Disclosure

References

Associated Data

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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