Laparoscopic radical gastrectomy is an effective minimally invasive procedure for the treatment of gastric cancer, but may cause moderate-to-severe abdominal wall pain and visceral pain that negatively affects postoperative rehabilitation (1). Appropriate postoperative pain management was beneficial for the patients’ recovery (2, 3). Patient-controlled intravenous analgesia (PCIA) with opioids was usually given to manage this postoperative pain (4). However, adverse events of PCIA like nausea, vomiting, lethargy, respiratory depression, skin pruritus and gastrointestinal dysfunction should be concerned (5). Kim et al. (6) showed that the combined use of non-steroidal anti-inflammatory drugs (NSAIDs) in patients treated with laparoscopic radical gastrectomy achieved an acceptable postoperative analgesia and a reduced consumption of postoperative opioids, but increased incidences of anastomotic leakage, duodenal stump leakage and intra-abdominal bleeding. Before anesthesia, rectus abdominis or rectus abdominis plane block combined with PCIA provides an effective postoperative analgesia for patients treated with laparoscopic radical gastrectomy (7, 8). However, nerve blocks have disadvantages of block failure, wrong-site blocks, nerve injury and local anesthetic poisoning. Postoperative epidural analgesia offers the same analgesic effect as PCIA on patients undergoing laparoscopic radical gastrectomy, whereas the former significantly increases the incidence of postoperative hypotension and urinary storage (9, 10). An effective and safe postoperative analgesia regimen is urgently needed for patients undergoing laparoscopic radical gastrectomy.

Postoperative pain, a type of inflammatory pain, is caused by peripheral tissue damage involving central and peripheral sensitization mechanisms (11, 12). Habibi et al. (13) and Ezzatvar et al. (14) indicated that central sensitization is the main cause of prolonged pain and poor analgesic effect. Perioperative acupuncture was reported to achieve the postoperative analgesic effect with less consumptions of analgesic drugs, by blocking harmful stimuli, reducing peripheral and central sensitization and inhibiting neuroplasticity (15). Acupuncture is a traditional Chinese medicine (TCM) technique with the recognized function in relieving pain (16, 17). The TCM theory believes that a congenital holographic system on the cheek is a continuous projection of the human body (Figure 1A) (18). Based on this, buccal acupuncture, as an emerging pain-free acupuncture therapy, stimulates 16 specific acupoints on the cheek to treat physical and mental diseases, including the chronic pain (Figure 1B). A growing body of evidence has supported the regulatory effects of buccal acupuncture on postoperative analgesia and viscera function with a high safety (19, 20). The present study explored the influence of buccal acupuncture before general anesthesia induction on postoperative analgesia and perioperative stress response in elderly patients undergoing laparoscopic radical gastrectomy and the underlying mechanism.

Buccal acupuncture is a new type of microneedling created by Wang Yongzhou (23), abiding by the theory that the physiology of the human body can be projected onto a holographic acupoint system visualized on the cheek. In a clinical trial involving 630 patients with limb pain and 100 patients with visceral pain, buccal acupuncture was validated for its rapid, reliable and systemic therapeutic efficacy. Moreover, various races can benefit from buccal acupuncture (18). In the present study, we proved that the use of buccal acupuncture before general anesthesia induction significantly reduced the consumption of intraoperative anesthetic drugs and postoperative analgesic drugs, and alleviated perioperative stress response and inflammatory response in elderly patients undergoing laparoscopic radical gastrectomy.

The 6th–10th thoracic vertebrae (T₆–T₁₀) provide the sensory innervation of the stomach, causing abdominal wall and visceral pain after surgery (25). Appropriate postoperative analgesia methods were conducive to patients’ recovery (2, 3). The traditional Chinese medicine (TCM) theory believed that the liver, gallbladder, spleen and stomach are harbored in the Middle Jiao, and the lower abdomen and urogenital reproduction in the Lower Jiao. Yi et al. (20) showed that the aging curve of the analgesic effect of buccal acupuncture was inherent and specific, and did not change with the number of treatments. In addition, they reported an obvious analgesic effect of buccal acupuncture starting at 5 min and peaking at 30 min. The analgesic effect of buccal acupuncture manifested as a temporal change with the rapid onset of analgesia, and increased in pain threshold and stability without being influenced by multiple times of acupunctures. We performed buccal acupuncture on the acupoints of the left shoulder point, bilateral acupoints of Middle Jiao and Lower Jiao for 30 min before general anesthesia induction in patients treated with laparoscopic radical gastrectomy. Consistent with previous data, the VAS scores within 24 h postoperatively were significantly lower in patients treated with buccal acupuncture than those of controls (17).

Surgical procedures of laparoscopic radical gastrectomy, anesthesia stimulation, establishment of CO₂ pneumoperitoneum and hypercapnia resulted in perioperative stress response, intraoperative hemodynamic fluctuations and postoperative pain (11, 12). Kurni et al. (26) verified that stress-related indicators like plasma Cor level are positively correlated with the intensity and duration of stimuli. The use of buccal acupuncture before general anesthesia induction significantly lowered peripheral levels of BP, E, NE, Cor and CRP within 24 h postoperatively, indicating the relieved postoperative stress response. Surgical trauma aggravated postoperative pain and inflammatory response by releasing inflammatory mediators, which could be alleviated by an effective preoperative regional anesthesia to inhibit the transmission of trauma and pain stimulation to the advanced center (14, 27). IL-6 is the earliest released and highly sensitive proinflammatory factor, closely related to the severity of surgical trauma, body immune status and prognosis (28). IL-10, as an inflammatory suppressor, inhibits nuclear factor activity and promotes neutrophil apoptosis (29). In this study, decreased IL-6 and increased IL-10 levels within 24 h postoperative in Group B suggested the role of buccal acupuncture in balancing the pro- and anti-inflammatory signals.

The regulatory effect of buccal acupuncture on inflammatory response is probably attributed to the blockage of pain signal to the central nervous system (15). Wang et al. (17) demonstrated the synergistic analgesic effect of acupuncture by relieving oxidative stress and inflammatory response, with the direct or indirect involvement of the nervous and humoral system. In a white rabbit model of rheumatoid arthritis (30), buccal acupuncture effectively relieved the pain by affecting the release of β-endorphin (β-EP) and cholecystokinin octapeptide (CCK-8) in cerebrospinal fluid. β-EP produces the analgesic effect by blocking pain signals via sensitizing the endogenous opioid peptide (EOP) receptors in neuronal terminals, or activating receptors with gray matter distribution around the brainstem aqueduct (31, 32). CCK-8 is a strong endogenous anti-opioid peptide with the central anti-opioid analgesic effect. It contributes to pain relief through reducing the total number of μ receptors, decreasing the affinity of κ receptors and inhibiting the binding force between opioid and receptors (33). Characterized by the analgesic time-effect, the use of buccal acupuncture in rabbits increased the content of 5-HT and decreases the ratio of NE/5-HT in the hypothalamus (30, 34).

The safety profile of buccal acupuncture was examined. There were no significant differences in the incidences of drowsiness, respiratory depression and skin pruritus between groups. The significantly lower incidence of PONV in Group B than in Group C could be explained by the greater consumption of postoperative analgesic drugs when PCIA was used alone (35). Additionally, blockage of Qi movement in the Middle Jiao caused gastrointestinal symptoms (36). We believed that buccal acupuncture on bilateral acupoints of the Middle Jiao effectively removed Qi stagnation and thus relieved PONV (37).

There were some limitations in this study. First of all, it was a prospective, outcome assessor-blinded RCT. We failed to find a suitable placebo in the control group to achieve double blinding. However, during the operation, all patients’ head and face were covered by a surgical scarf and head frame, so that the assessor was not aware of the patients’ grouping. Secondly, the exclusion of patients with suspected intubation difficulty (Mallampati Scoring of Class II and above) may cause potential biases. At last, the use of tramadol for postoperative salvage analgesia may influence the occurrence of PONV. Taken together, buccal acupuncture reduces perioperative consumption of analgesic drugs and favors the postoperative analgesic effect and recovery in elderly patients undergoing laparoscopic radical gastrectomy with a high safety. This method can provide reference for postoperative analgesia in other surgical patients.

In conclusion, the use of buccal acupuncture before general anesthesia induction reduces perioperative consumption of analgesic drugs and favors the postoperative analgesic effect and recovery in elderly patients undergoing laparoscopic radical gastrectomy by relieving postoperative stress response and inflammatory response, which acceptable efficacy and safety.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving humans were approved by Medical Ethics Committee of Jiangning Hospital affiliated to Nanjing Medical University. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

D-xZ: Data curation, Methodology, Visualization, Investigation, Writing – original draft. Y-lY: Investigation, Conceptualization, Methodology, Writing – original draft. LY: Data curation, Investigation, Writing – original draft. Y-yZ: Investigation, Methodology, Writing – original draft. Y-yX: Data curation, Software, Writing – original draft. WW: Conceptualization, Funding acquisition, Methodology, Project administration, Writing – review & editing. JL: Conceptualization, Formal analysis, Supervision, Writing – review & editing. W-yY: Supervision, Validation, Writing – review & editing.