Efficacy and safety of acupuncture-point stimulation combined with opioids for the treatment of moderate to severe cancer pain: a network meta-analysis of randomized controlled trials

Abstract

Background: Pain is one of the most common and troublesome symptoms of cancer. Although potential positive effects of acupuncture-point stimulation (APS) on cancer pain have been observed, knowledge regarding the selection of the optimal APS remains unclear because of a lack of evidence from head-to-head randomized controlled trials (RCTs).

Objective: This study aimed to carry out a network meta-analysis to compare the efficacy and safety of different APS combined with opioids in treating moderate to severe cancer pain and rank these methods for practical consideration.

Methods: A comprehensive search of eight electronic databases was conducted to obtain RCTs involving different APS combined with opioids for moderate to severe cancer pain. Data were screened and extracted independently using predesigned forms. The quality of RCTs was appraised with the Cochrane Collaboration risk-of-bias tool. The primary outcome was the total pain relief rate. Secondary outcomes were the total incidence of adverse reactions, the incidence of nausea and vomiting, and the incidence of constipation. We applied a frequentist, fixed-effect network meta-analysis model to pool effect sizes across trials using rate ratios (RR) with their 95% confidence intervals (CI). Network meta-analysis was performed using Stata/SE 16.0.

Results: We included 48 RCTs, which consisted of 4,026 patients, and investigated nine interventions. A network meta-analysis showed that a combination of APS and opioids was superior in relieving moderate to severe cancer pain and reducing the incidence of adverse reactions such as nausea, vomiting, and constipation compared to opioids alone. The ranking of total pain relief rates was as follows: fire needle (surface under the cumulative ranking curve (SUCRA) = 91.1%), body acupuncture (SUCRA = 85.0%), point embedding (SUCRA = 67.7%), auricular acupuncture (SUCRA = 53.8%), moxibustion (SUCRA = 41.9%), transcutaneous electrical acupoint stimulation (TEAS) (SUCRA = 39.0%), electroacupuncture (SUCRA = 37.4%), and wrist-ankle acupuncture (SUCRA = 34.1%). The ranking of total incidence of adverse reactions was as follows: auricular acupuncture (SUCRA = 23.3%), electroacupuncture (SUCRA = 25.1%), fire needle (SUCRA = 27.2%), point embedding (SUCRA = 42.6%), moxibustion (SUCRA = 48.2%), body acupuncture (SUCRA = 49.8%), wrist-ankle acupuncture (SUCRA = 57.8%), TEAS (SUCRA = 76.3%), and opioids alone (SUCRA = 99.7%).

Conclusions: APS seemed to be effective in relieving cancer pain and reducing opioid-related adverse reactions. Fire needle combined with opioids may be a promising intervention to reduce moderate to severe cancer pain as well as reduce opioid-related adverse reactions. However, the evidence was not conclusive. More high-quality trials investigating the stability of evidence levels of different interventions on cancer pain must be conducted.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#searchadvanced, identifier CRD42022362054.

Keywords: acupuncture-point stimulation; cancer pain; network meta-analysis; opioid; supplementary alternative therapy.

Figure 1

PRISMA flow diagram.

Figure 2

Network meta-analysis of total pain relief rate. The bold font indicates a statistically significant difference between the two treatments. (A) Network plot showing comparisons in efficacy between nodes (blue circles), each representing a unique intervention. Each node’s size is proportional to the total number of randomly assigned participants receiving the treatment. The width of each connecting line is proportional to the number of trial-level comparisons between the two nodes. (B) Forest plot of the network meta-analysis comparing the efficacy of each treatment. (C) Schematic detailing the most efficacious treatments according to the surface under the cumulative ranking curve analysis (SUCRA). A, Body acupuncture combined with opioids; B, moxibustion combined with opioids; C, electroacupuncture combined with opioids; D, auricular acupuncture combined with opioids; E, point embedding combined with opioids; F, TEAS combined with opioids; G, wrist–ankle acupuncture combined with opioids; H, fire needle combined with opioids; I, opioids.

Figure 3

Network meta-analysis of total incidence of the adverse reactions. (A) Network plot showing comparisons in security between each intervention. (B) Forest plot of the network meta-analysis comparing the security of each treatment. (C) Schematic detailing the safest treatments according to the surface under the cumulative ranking curve analysis (SUCRA). A, Body acupuncture combined with opioids; B, moxibustion combined with opioids; C, electroacupuncture combined with opioids; D, auricular acupuncture combined with opioids; E, point embedding combined with opioids; F, TEAS combined with opioids; G, wrist–ankle acupuncture combined with opioids; H, fire needle combined with opioids; I, opioids.

Figure 4

Network meta-analysis of the incidence of nausea and vomiting. (A) Network plot showing comparisons in the incidence of nausea and vomiting between each intervention. (B) Forest plot of the network meta-analysis comparing the incidence of nausea and vomiting in each treatment. (C) Schematic detailing the most secure treatments according to the surface under the cumulative ranking curve analysis (SUCRA). A, Body acupuncture combined with opioids; B, moxibustion combined with opioids; C, electroacupuncture combined with opioids; D, auricular acupuncture combined with opioids; E, point embedding combined with opioids; F, TEAS combined with opioids; G, wrist–ankle acupuncture combined with opioids; H, fire needle combined with opioids; (I) opioids.

Figure 5

Network meta-analysis of the incidence of constipation. (A) Network plot showing comparisons in the incidence of constipation between each intervention. (B) Forest plot of the network meta-analysis comparing the incidence of constipation in each treatment. (C) Schematic detailing the most secure treatments according to the surface under the cumulative ranking curve analysis (SUCRA). A, Body acupuncture combined with opioids; B, moxibustion combined with opioids; C, electroacupuncture combined with opioids; D, auricular acupuncture combined with opioids; E, point embedding combined with opioids; F, TEAS combined with opioids; G, wrist–ankle acupuncture combined with opioids; H, fire needle combined with opioids; I, opioids.

Figure 6

Synthetic sorting bubble diagram plot for outcomes. (A) Bubble diagram plot for the total pain relief rate and adverse reactions; (B) bubble diagram plot for total pain relief rate and nausea and vomiting. (C) Bubble diagram plot for total pain relief rate and constipation. (D) Bubble diagram plot for nausea and vomiting, and constipation. Note: Interventions with the same color belong to the same regimen, and interventions located in the lower left corner indicate optimal therapy for two different outcomes. A, Body acupuncture combined with opioids; B, moxibustion combined with opioids; C, electroacupuncture combined with opioids; D, auricular acupuncture combined with opioids; E, point embedding combined with opioids; F, TEAS combined with opioids; G, wrist–ankle acupuncture combined with opioids; H, fire needle combined with opioids; I, opioids.

Figure 7

Funnel plots. (A) Total pain relief rate. (B) Total adverse reactions. (C) The incidence of Nausea and vomiting. (D) The incidence of constipation. A, Body acupuncture combined with opioids; B, moxibustion combined with opioids; C, electroacupuncture combined with opioids; D, auricular acupuncture combined with opioids; E, point embedding combined with opioids; F, TEAS combined with opioids; G, wrist–ankle acupuncture combined with opioids; H, fire needle combined with opioids; I, opioids.