Effects of Preemptive Analgesia Using Wrist-Ankle Acupuncture on Postoperative Pain and Urinary Retention After Haemorrhoidectomy: A Randomised, Three-Arm, Clinical Trial [Response to Letter]

Dear editor

Thank you very much for your careful reading of and thoughtful comments on our paper “Effects of Preemptive Analgesia Using Wrist‑Ankle Acupuncture on Postoperative Pain and Urinary Retention After Haemorrhoidectomy: A Randomised, Three‑Arm, Clinical Trial” published in the Journal of Pain Research.¹ The three methodological concerns you raised, regarding blinding and placebo control, the discrepancy between sample size estimation and actual enrolment, and the incomplete chain of evidence linking short-term outcomes to long‑term ERAS benefits, are all highly pertinent and constructive. We fully accept these criticisms and respond to each point below.

First, Regarding the Limitations of Blinding and Placebo Control

The lack of operator blinding and the absence of a sham acupuncture or non‑acupoint control is indeed a long standing challenge in acupuncture RCTs. In our paper, we honestly acknowledged this limitation. At the time of trial design, we prioritised assessor blinding and statistical blinding, all outcome assessors and data analysts were blinded to group allocation, in order to minimise detection bias. Nevertheless, your concern that patients’ awareness of receiving an active intervention may have confounded the true analgesic efficacy through expectancy effects is entirely valid.

You noted that “the VAS differences between the preemptive and immediate groups were non‑significant prior to 6 hours postoperatively, with divergence emerging mainly in the middle‑to‑late phases”. Regarding this point, we hope to further conduct mechanistic studies on preemptive wrist-ankle acupuncture in the future, aiming to obtain more objective and scientific evidence from physiological or serological perspectives.

Our second RCT (randomised, three‑arm, sham‑controlled trial), which is near completion, has been designed specifically to address this limitation. In that new study, we have incorporated a rigorous sham‑acupuncture control (non-penetrating sham acupuncture) and adopted a stricter blinding design to quantify and isolate placebo effects, directly responding to your key methodological concern.

Second, Regarding the Discrepancy Between Sample Size Estimation and Actual Enrollment

Your point that “the initial calculation required 38 patients per group, but 275 were eventually enrolled, exceeding the target by more than twofold” deserves clarification. The sample‑size calculation reported in the Methods section (based on PASS 15.0, D=1.0, Sigma=1.2, M=6, 1‑β=0.90) was derived from a relatively conservative pairwise‑comparison strategy. However, during the actual conduct of the trial, two considerations led to the larger sample:

First, the need for subgroup analyses—we had pre‑planned stratification by baseline analgesic type (Med1 vs Med2), which required sufficient power within each subgroup. Second, smooth recruitment—during the planned enrolment period (June 2024 to March 2025), more eligible patients than expected were available, and we expanded recruitment without extending the study period.

Regarding your concern that “excessively large sample sizes can inflate statistical sensitivity, rendering small differences—such as a VAS difference of 0.55 points (P=0.006), statistically significant without necessarily reaching the MCID”, we have specifically incorporated MCID (Minimal Clinically Important Difference) analysis as a specified secondary outcome in our new study.

Third, Regarding the Incomplete Evidence Chain Linking Short‑term Outcomes to Long‑term ERAS Benefits

You pointed out that “the observational endpoint was restricted to 24 hours postoperatively, without capturing validated sleep scores, anxiety scales, time to first flatus/ambulation, or length of hospital stay”, and that “verifying a reduction in chronic postsurgical pain (CPSP) requires a follow‑up duration of at least 3 months.” We fully agree. In the Discussion section of our paper, we clearly stated that “longer‑term outcomes, such as chronic pain incidence or wound healing, were not assessed” as a limitation.

Once again, we are particularly grateful that your comments have directly influenced the design of our subsequent research, this is exactly how scientific discourse should advance the field. Your comments have not only helped us more clearly recognise the limitations of our published study but have also directly inspired the design optimisation of our subsequent research. We look forward to the possibility of deeper academic exchange and collaboration with you in the future.

Yours sincerely,

Pingping He

(on behalf of all co‑authors).

Disclosure

The author has no financial or personal relationships to report in this communication.