Traditional Chinese medicine acupuncture for postoperative nausea and vomiting after cholecystectomy: Mechanistic insights and clinical evidence

Abstract

Postoperative nausea and vomiting (PONV) remain a frequent and distressing complication following cholecystectomy, impairing recovery and patient satisfaction. Despite the availability of pharmacologic therapies, PONV continues to occur at a substantial rate. While conventional pharmacologic antiemetics are widely used, their efficacy is limited by incomplete symptom control and potential adverse effects. In recent years, traditional Chinese medicine acupuncture has emerged as a promising non-pharmacological adjunct with both preventive and therapeutic value in PONV management. This review synthesizes current evidence on the mechanisms and clinical efficacy of acupuncture for PONV after cholecystectomy. Acupuncture modulates the autonomic nervous system, enhances gastrointestinal motility, and regulates key neurotransmitters such as serotonin and dopamine, collectively restoring neuro-humoral balance and suppressing emetic pathways. Clinical trials and meta-analyses consistently demonstrate that acupuncture, particularly stimulation of the Neiguan point, significantly reduces PONV incidence and severity with minimal adverse effects. Various acupuncture modalities, including manual acupuncture, electroacupuncture, and transcutaneous electrical acupoint stimulation, have shown similar antiemetic potential in perioperative settings. Based on accumulating evidence, integrating Neiguan-focused acupuncture into multimodal antiemetic regimens may provide added benefit, although further research is needed to standardize implementation protocols. Future research should focus on standardizing acupuncture protocols and elucidating molecular mechanisms to strengthen evidence-based application in surgical practice.

Key Words: Traditional Chinese medicine acupuncture; Cholecystectomy; Nausea and vomiting; Perioperative management; Non-pharmacological treatment

Core Tip: Postoperative nausea and vomiting frequently complicates recovery after cholecystectomy despite advances in pharmacologic prophylaxis. This review summarizes recent mechanistic and clinical evidence supporting traditional Chinese medicine acupuncture as a safe, effective adjunctive therapy. Acupuncture modulates autonomic function, enhances gastrointestinal motility, and balances neurotransmitter signaling to reduce postoperative nausea and vomiting severity. Stimulation at Neiguan demonstrates consistent antiemetic benefits, suggesting that acupuncture may be integrated into multimodal perioperative management to optimize recovery and improve patient satisfaction.

INTRODUCTION

Postoperative nausea and vomiting (PONV) are one of the most common and unpleasant complications after laparoscopic cholecystectomy (LC), affecting up to half of patients and impairing recovery, comfort, and satisfaction[1-3]. Despite refinements in anesthesia and surgical techniques, the incidence of PONV remains stubbornly high. It results from multiple interacting factors - including patient characteristics, anesthetic agents, and surgical stimuli - all of which influence emetic pathways[4-6]. Conventional antiemetic drugs such as 5-hydroxytryptamine (5-HT) 3 receptor antagonists, dexamethasone, and dopamine antagonists can reduce symptoms but often provide incomplete relief and may cause adverse reactions. Persistent or refractory PONV continues to challenge perioperative management.

Traditional Chinese medicine (TCM) acupuncture has gained growing attention as a non-pharmacologic adjunct with demonstrated safety and potential benefit. Acupuncture exerts complex neuroregulatory actions that modulate autonomic balance, promote gastrointestinal motility, and regulate neurotransmitters - mechanisms increasingly supported by contemporary biomedical studies[7,8]. Among the various acupoints, Neiguan (PC6) stimulation shows consistent benefit across a range of perioperative settings.

Recent meta-analyses report that acupuncture can significantly reduce the incidence and severity of PONV and lessen the need for rescue antiemetics[7,8]. Nevertheless, variability in acupuncture protocols and study quality limits widespread adoption and calls for more standardized investigation. This review aims to synthesize current mechanistic evidence and recent clinical findings from the past five years regarding acupuncture - particularly PC6 stimulation - for PONV after LC, and to outline its clinical integration prospects and future research priorities (Figure 1).

Figure 1 Mechanistic pathways through which acupuncture mitigates postoperative nausea and vomiting following cholecystectomy. PONV: Postoperative nausea and vomiting; LC: Laparoscopic cholecystectomy; NTS: Nucleus of the solitary tract; ANS: Autonomic nervous system; GI: Gastrointestinal; ICC: Interstitial cells of Cajal; QoR: Quality of recovery; PC6: Neiguan; ST36: Zusanli; LI4: Hegu; TESA: Transcutaneous electrical acupoint stimulation; 5-HT: 5-Hydroxytryptamine; CGRP: Calcitonin gene-related peptide; GABA: Gamma-aminobutyric acid; VIP: Vasoactive intestinal peptide.

PATHOPHYSIOLOGICAL MECHANISMS OF PONV AFTER CHOLECYSTECTOMY

Mechanisms of PONV occurrence and influencing factors

PONV is a multifactorial complication commonly observed after LC, primarily resulting from the combined effects of anesthetic agents, surgical stimuli, and individual patient susceptibility[2-4]. Figure 1 provides an integrated overview of how these surgical and anesthetic factors disrupt neuro-endocrine and gastrointestinal regulatory pathways, forming the conceptual framework for the mechanistic discussion that follows. Anesthetic drugs, especially volatile anesthetics and opioids, are well-established triggers for PONV due to their action on central and peripheral emetic pathways. Surgical stimulation, particularly manipulation of the biliary tract during cholecystectomy, exacerbates gastrointestinal irritation and inflammatory responses, further predisposing patients to PONV. Notably, the unique aspects of cholecystectomy, such as bile duct handling and intra-abdominal inflammation, contribute to gastrointestinal dysmotility, amplifying nausea and vomiting risk. Neurotransmitters including serotonin (5-HT), dopamine, and neuropeptides play pivotal roles in the emetic reflex arc. The release of serotonin from enterochromaffin cells in the gastrointestinal tract is believed to activate 5-HT 3 receptors on vagal afferents, transmitting signals to the brainstem vomiting center. Dopaminergic pathways, particularly via D2 receptors, also modulate nausea and vomiting. Recent transcriptomic analyses in animal models have demonstrated alterations in neurotransmitter-related gene expression in the nucleus of the solitary tract, implicating gamma-aminobutyric acid type B receptor receptor-mediated signaling and catecholamine neurotransmission in PONV pathogenesis. Pharmacologic activation of gamma-aminobutyric acid type B receptor receptors with baclofen has shown antiemetic effects in preclinical studies, suggesting potential therapeutic targets. Clinically, factors such as female gender, younger age, non-smoking status, history of motion sickness or previous PONV, and opioid use are significant predictors of PONV. Anxiety and preoperative fasting duration also influence PONV incidence. Comprehensive risk assessment tools like the Apfel score incorporate these variables to stratify patients and guide prophylaxis. Multimodal anesthesia techniques that reduce opioid consumption, such as lidocaine infusion or opioid-free anesthesia, have demonstrated reductions in PONV frequency. Beyond drug-based therapy, several non-pharmacological methods - most notably acupressure and acupuncture - have been reported to lessen postoperative nausea and reduce the requirement for rescue antiemetic medication[7]. The occurrence of PONV following cholecystectomy, therefore, reflects not a single cause but a multifactorial process shaped by pharmacologic influences, surgical technique, and individual patient susceptibility. Acting through overlapping neurochemical circuits, these elements collectively highlight the importance of tailoring preventive and therapeutic approaches to each patient[9-12]. A concise overview of these major risk factors and mechanistic pathways is summarized in Table 1 to facilitate clearer conceptual understanding. Taken together, these mechanisms outline how postoperative physiological dysregulation creates multiple points at which acupuncture may exert modulatory effects, providing a rationale for its therapeutic potential in PONV management.

Table 1 Major risk factors and mechanistic contributors to postoperative nausea and vomiting after laparoscopic cholecystectomy.

Category	Specific factors	Mechanistic pathways involved
Patient-related	Female sex; younger age; history of motion sickness or prior PONV; non-smoking status	Heightened serotonergic sensitivity; autonomic imbalance
Anesthetic-related	Volatile anesthetics; opioids	Activation of 5-HT 3 and D2 pathways; delayed gastric emptying; vagal stimulation
Surgical-related	Bile duct manipulation; pneumoperitoneum	Gastrointestinal irritation; inflammatory signaling; altered bile acid dynamics
Physiological and biochemical	Altered gut microbiota; bile acid–serotonin interactions	Increased colonic 5-HT production; dysregulated motility
Perioperative factors	Anxiety; prolonged fasting; hemodynamic instability	Autonomic dysregulation; impaired gastrointestinal perfusion

PONV: Postoperative nausea and vomiting; 5-HT: 5-Hydroxytryptamine.

Effects of cholecystectomy on gastrointestinal motility

Laparoscopic removal of the gallbladder often produces marked changes in gastrointestinal motility, and these alterations are thought to play a central role in PONV[8,13]. During the procedure, manipulation of the gallbladder and bile ducts interferes with normal bile flow and modifies the pattern of bile secretion. Such disturbances can influence gastrointestinal reflex activity and disrupt coordinated motility. Clinically, this frequently presents as delayed gastric emptying and sluggish intestinal peristalsis, both of which increase the likelihood of nausea and vomiting after surgery. The pathophysiology involves both mechanical and neurochemical factors. For instance, changes in bile duct pressure and bile acid composition may influence afferent signaling via the vague nerve, modulating motility and emetic responses[13,14]. Studies have shown that post-cholecystectomy patients exhibit increased gastrointestinal transit times and altered motility patterns, which correlate with symptom severity. Moreover, the gut microbiota undergoes compositional changes after cholecystectomy, influencing bile acid metabolism and serotonin (5-HT) production in the colon[15]. Elevated colonic 5-HT, stimulated by secondary bile acids, enhances colonic motility and may exacerbate diarrhea and nausea. Experimental models demonstrate that these microbial and biochemical alterations contribute to gastrointestinal dysfunction post-cholecystectomy. Additionally, stress responses related to surgery can induce apoptosis of interstitial cells of Cajal in the gallbladder[16], pacemaker cells critical for coordinated motility, further impairing gastrointestinal function. Pharmacological agents used perioperatively, such as neuromuscular blockade reversal drugs, also impact gastrointestinal motility; sugammadex has been associated with earlier recovery of bowel function compared to anticholinesterase/anticholinergic combinations. Hemodynamic factors like intraoperative hypotension have been linked to increased PONV, possibly via compromised gastrointestinal perfusion affecting motility. Overall, the interplay of surgical trauma, bile flow disruption, neurohumoral changes, microbial shifts, and pharmacologic influences culminates in impaired gastrointestinal motility after cholecystectomy, heightening the risk for PONV[15-18].

Clinical assessment of related risk factors

Accurate preoperative assessment of risk factors for PONV is essential to tailor prophylactic and therapeutic interventions effectively[1-3]. Established clinical predictors include demographic variables such as female sex and younger age, with women, especially premenopausal, exhibiting higher incidences of PONV and postoperative pain[19,20]. Smoking status inversely correlates with PONV risk, possibly due to nicotine’s modulatory effects on neurotransmitter systems, although nicotine patch application has not consistently demonstrated benefit in non-smokers. A personal or family history of motion sickness or previous PONV significantly increases susceptibility. The type and duration of anesthesia and surgery also influence risk; longer operative times and inhalational anesthetics are associated with higher PONV incidence. Opioid use, both intraoperatively and postoperatively, remains a potent risk factor, underscoring the importance of opioid-sparing multimodal analgesia protocols. Risk stratification tools such as the Apfel and Koivuranta scores have been validated in various populations, including LC patients, and facilitate identification of high-risk individuals. Recent studies have explored novel predictors such as gastric antral cross-sectional area measured by ultrasound, which may reflect gastric distension and correlate with PONV occurrence. Additionally, gut microbiota composition has emerged as a potential biomarker, with certain bacterial genera inversely associated with PONV severity[21]. In clinical practice, thorough preoperative evaluation incorporating these factors enables individualized prophylaxis, including pharmacologic agents like 5-HT 3 receptor antagonists, dexamethasone, and neurokinin-1 receptor antagonists, as well as non-pharmacologic measures such as acupuncture. Early identification of high-risk patients allows for optimized antiemetic regimens and improved postoperative outcomes[19-22].

MECHANISMS OF TCM ACUPUNCTURE IN ALLEVIATING PONV AFTER CHOLECYSTECTOMY

Regulatory effects of acupuncture on the nervous system

Acupuncture exerts significant modulatory effects on the nervous system, which play a pivotal role in mitigating PONV following cholecystectomy. As outlined in Figure 1, these effects directly target the dysregulated autonomic, gastrointestinal, and neurotransmitter pathways implicated in PONV, thereby providing a mechanistic basis for symptom improvement. From a TCM perspective, these physiological effects correspond to the regulation of qi flow, harmonization of the stomach, and restoration of the balance between ascending and descending functional activities, providing a conceptual bridge between classical TCM theory and modern biomedical mechanisms. By stimulating specific acupoints, acupuncture activates afferent sensory nerve fibers that transmit signals to the central nervous system, particularly influencing brain regions involved in emesis control. This neuromodulation may lead to the suppression of excitability within the vomiting center and associated neural circuits, thereby inhibiting the initiation and propagation of nausea and vomiting reflexes. Experimental studies have demonstrated that acupuncture induces a parasympathetic-dominant autonomic nervous system response, characterized by decreased heart rate and altered heart rate variability, indicating enhanced vagal tone and reduced sympathetic activity[23-25]. Such autonomic adjustments improve gastrointestinal function and contribute to the attenuation of PONV. Furthermore, acupuncture influences the activity of the vague nerve and sympathetic nerves, which are integral to gastrointestinal motility and secretion. By modulating these neural pathways, acupuncture enhances gastric emptying and normalizes gastrointestinal motility disrupted by surgical stress and anesthesia[26-28]. The hypothalamus, a critical autonomic regulatory center, is also involved in acupuncture’s effects; acupuncture signals transmitted to the hypothalamus orchestrate downstream autonomic responses that restore homeostasis and reduce PONV[29]. Additionally, neuroimaging and neurophysiological studies have identified that acupuncture stimulation at specific points such as PC6, Zusanli (ST36), and auricular acupoints activates brain regions associated with autonomic regulation and visceral sensory processing, further supporting its central regulatory role[30,31]. Collectively, acupuncture’s regulation of the nervous system involves a complex interplay between peripheral sensory input, central autonomic nuclei, and efferent autonomic pathways, culminating in the suppression of emetic reflexes and improvement of gastrointestinal function after cholecystectomy.

Effects of acupuncture on gastrointestinal motility

Acupuncture significantly influences gastrointestinal motility, a critical factor in the pathogenesis of PONV after cholecystectomy. Surgical stress and anesthesia often impair gastric emptying and intestinal peristalsis, leading to gastrointestinal dysfunction and increased incidence of PONV. Acupuncture promotes gastrointestinal motility by enhancing gastric emptying and stimulating intestinal peristalsis, thereby alleviating functional gastrointestinal disturbances. Clinical and experimental studies have shown that acupuncture at acupoints such as ST36, PC6, and Tianshu accelerates gastric emptying and improves intestinal transit, facilitating the recovery of normal gastrointestinal function postoperatively[27,32,33]. The mechanisms underlying these effects involve modulation of the enteric nervous system, autonomic nervous system, and gastrointestinal hormones. Acupuncture regulates the secretion of gastrointestinal peptides including motilin, gastrin, vasoactive intestinal peptide, and somatostatin, which play essential roles in coordinating smooth muscle contractions and digestive secretions[32,34,35]. Acupuncture appears to influence gastrointestinal motility in several interconnected ways. One important mechanism involves the interstitial cells of Cajal - the pacemaker cells that coordinate gut movement - whose activity and recovery after surgical injury can be enhanced through acupuncture stimulation[36,37]. Experimental work with electroacupuncture at ST36 further suggests modulation of local inflammation and oxidative stress within the gastrointestinal tract, which in turn helps restore mucosal integrity and motor function[38]. Interestingly, acupuncture exerts a bidirectional effect on peristalsis: It may either activate or dampen intestinal contractions depending on the physiological context, thereby supporting postoperative homeostasis[39]. Through its combined impact on neural signaling and hormonal balance, acupuncture ultimately promotes smoother gastrointestinal motility and lessens both the incidence and intensity of PONV following cholecystectomy.

Regulation of neurotransmitters by acupuncture

The antiemetic effect of acupuncture appears to depend largely on its ability to influence neurotransmitters that govern nausea pathways. Among these chemical mediators, serotonin (5-HT), dopamine, and substance P play pivotal roles in generating and transmitting emetic signals. By modulating their release and receptor activity, acupuncture can interfere with the neural circuits that trigger PONV. Acupuncture has been shown to influence the release and receptor activity of these neurotransmitters, thereby attenuating the emetic response. Specifically, acupuncture may reduce the excessive release of 5-HT in the gastrointestinal tract and central nervous system, which is known to activate 5-HT 3 receptors that trigger nausea and vomiting reflexes[40-42]. By downregulating 5-HT and its receptors, acupuncture diminishes the afferent signaling to the vomiting center. Similarly, acupuncture modulates dopaminergic pathways by decreasing dopamine levels or altering dopamine receptor activity, contributing to antiemetic effects[40,43]. Additionally, acupuncture affects other neurotransmitters such as gamma-aminobutyric acid, which exerts inhibitory effects on emesis, and neuropeptides including calcitonin gene-related peptide and substance P, which are involved in neurogenic inflammation and sensitization processes[40,41]. Acupuncture also mitigates neuroinflammation by regulating inflammatory cytokines and glial cell activation, which indirectly influences neurotransmitter systems and reduces postoperative emetic symptoms[29,44]. Furthermore, neurotransmitter modulation by acupuncture extends to the autonomic nervous system, balancing sympathetic and parasympathetic activities that affect gastrointestinal function and emesis control[23,25]. These multifaceted effects on neurotransmitter release, receptor expression, and neuroinflammatory pathways highlight acupuncture’s comprehensive mechanism in reducing PONV through neurochemical regulation. Despite these advances, the quality and consistency of existing mechanistic evidence warrant careful consideration.

In addition to these mechanistic insights, important limitations and ongoing controversies should be acknowledged. Current evidence is challenged by substantial heterogeneity in acupoint selection, stimulation parameters, and perioperative timing, which complicates comparison across studies. The use of sham acupuncture as a placebo control also remains problematic, as even minimal or superficial stimulation may elicit physiological responses, thereby narrowing the true difference between intervention and control groups. Moreover, reported effects on vagal activation, gastrointestinal motility, and neurotransmitter modulation vary across studies, suggesting that these mechanisms may not be uniformly reproducible and could depend on patient characteristics or methodological factors. Recognizing these uncertainties is essential for interpreting existing data and guiding the design of more rigorous mechanistic studies.

Evidence quality and current challenges

Although multiple mechanistic studies support the regulatory effects of acupuncture on autonomic function, gastrointestinal motility, and neurotransmitter balance, the current evidence base still presents limitations. Variability in acupoint selection, stimulation parameters, treatment timing, and outcome measures contributes to heterogeneity across studies. Many mechanistic findings rely on small-sample trials or preclinical work, which may affect generalizability. Additionally, methodological challenges such as blinding and placebo control complicate the interpretation of autonomic and neurochemical responses. These issues underscore the need for standardized protocols, larger mechanistic studies, and more rigorous trial designs to strengthen causal inference in future research.

In summary, TCM acupuncture alleviates PONV after cholecystectomy through integrated mechanisms involving central and peripheral nervous system modulation, enhancement of gastrointestinal motility via neuro-hormonal pathways, and regulation of key neurotransmitters and inflammatory mediators. These mechanisms collectively restore autonomic balance, improve gastrointestinal function, and suppress emetic signaling, supporting acupuncture as an effective adjunctive therapy in the perioperative management of cholecystectomy patients. With these mechanistic insights established, the clinical evidence further clarifies the extent to which acupuncture produces meaningful benefits in real-world perioperative settings.

CLINICAL EVIDENCE AND APPLICATION OF ACUPUNCTURE IN PONV MANAGEMENT AFTER CHOLECYSTECTOMY

Review of clinical trials of acupuncture for PONV after cholecystectomy

Multiple randomized controlled trials have demonstrated that acupuncture significantly reduces the incidence and severity of PONV following LC, establishing its clinical efficacy and safety in this context. A notable randomized controlled trial comparing acupuncture with parecoxib sodium in LC patients showed that acupuncture not only reduced postoperative pain scores but also significantly lowered PONV scores at 6 hours post-operation, indicating an early postoperative benefit in nausea and vomiting control[45]. The primary acupoint utilized in these studies is the PC6 point, which is consistently associated with stable antiemetic effects and minimal adverse events. In one randomized clinical study, intraoperative laser stimulation of the PC6 and Hegu acupoints was applied in conjunction with standard antiemetic prophylaxis. Patients receiving this combined approach reported fewer episodes of nausea and required less rescue medication within the first six hours after surgery compared with those given antiemetic drugs alone[46]. However, existing trials vary widely in acupoint selection, stimulation modality, treatment timing, and outcome definitions, creating substantial heterogeneity that complicates direct comparison and limits the interpretability of pooled findings. These observations highlight acupuncture’s supportive role in managing PONV, with PC6 standing out as a particularly responsive therapeutic point. Importantly, acupuncture was well tolerated in this setting; adverse effects were rare and generally mild. Taken together, evidence from randomized trials indicates that acupuncture - especially when targeting PC6 - offers an effective, safe, and non-pharmacological option to reduce PONV after cholecystectomy, contributing to smoother recovery and greater patient comfort in the immediate postoperative phase.

Advantages of combining acupuncture with drug therapy

When acupuncture is combined with standard antiemetic therapy, the two approaches appear to act in concert to control PONV after cholecystectomy. This integrative approach can strengthen the overall therapeutic effect while permitting a lower drug dose, thereby reducing medication-related side effects. Evidence from clinical studies supports this concept: Patients receiving acupuncture alongside antiemetic agents such as metoclopramide often report fewer nausea episodes and require fewer rescue doses, with recovery tending to occur more quickly. In one randomized trial, intraoperative laser stimulation of the PC6 and Hegu acupoints together with antiemetic prophylaxis may result in a markedly lower rate of nausea and a decreased need for rescue drugs within six hours after surgery compared with pharmacotherapy alone[46]. The combination may also help limit common adverse reactions to antiemetics - such as sedation or extrapyramidal symptoms - by enabling smaller dosages. Moreover, studies have noted earlier restoration of bowel function and shorter hospital stays when acupuncture is added to pharmacologic treatment, suggesting broader benefits for postoperative recovery. Similar patterns have been described in other clinical settings, where coupling acupuncture with medication enhances symptom relief and diminishes side effects[47]. Altogether, integrating acupuncture with antiemetic drug therapy provides a balanced approach that maximizes efficacy, minimizes risk, and supports faster convalescence after surgery.

Safety and patient compliance of acupuncture treatment

Clinical experience and published data indicate that acupuncture is generally safe and well tolerated, which makes it appropriate for a wide range of patients undergoing cholecystectomy. Reported side effects are uncommon and typically minor - for example, short-lived soreness at the needle site or slight bleeding - and seldom necessitate stopping treatment. Because of its very low complication rate, patients tend to adhere well to therapy, a factor that strongly influences clinical outcomes. Being a non-pharmacological intervention, acupuncture also avoids systemic toxicities from drugs and may be particularly helpful for individuals who cannot tolerate standard antiemetics.

Nevertheless, maintaining safety and patient confidence requires careful attention to technical standards and practitioner training. Proper instruction of acupuncturists and strict compliance with procedural guidelines are vital for minimizing risk and ensuring treatment quality. Investigations have highlighted several procedural points that contribute to safety, including appropriate needle retention time, precise acupoint selection - especially PC6 for the prevention of PONV - and meticulous aseptic technique[48]. In addition, educating patients about what to expect and emphasizing the procedure’s safety record can ease anxiety related to needles and improve acceptance[49]. Overall, acupuncture provides a low-risk, well-accepted option for managing PONV, provided it is delivered by trained professionals under standardized clinical conditions.

CONCLUSION

PONV remain a frequent and distressing complication after cholecystectomy. Accumulating mechanistic and clinical evidence suggests that acupuncture - particularly PC6 stimulation - may serve as a safe adjunct by modulating autonomic activity, improving gastrointestinal motility, and influencing key neurotransmitter pathways. These effects are broadly consistent with enhanced recovery after surgery principles, supporting its potential incorporation into multimodal, opioid-sparing antiemetic strategies. Although heterogeneity in study design and acupuncture techniques limits direct comparison, overall findings are encouraging. Future research should prioritize protocol standardization, biomarker-based identification of responders, and rigorously designed trials to clarify mechanisms and optimize clinical integration. Such advances will help guide evidence-based use of acupuncture in perioperative care and improve recovery quality for patients undergoing cholecystectomy.