In the study, the results were found as follows: 1) The VAS scores of visceral pains for Group O at 24 h and 72 h after surgery were lower than those for Group S; 2) The serum lgG concentration at T1 was lower than that at T0 in Group O, and the serum lgG concentration in Group O was higher than that in Group S at 72 h after the surgery. Additionally, Group O exhibited a higher serum concentration of IL-2 at T2 compared to Group S. Other immune indicators including C3, C4, IgA, IgE, IgM, CD3+, CD4+, CD8+ and CD4+/CD8+did not show significant changes after using oxycodone or sufentanil for PCIA. 3) The IL-10 concentration in T1 was higher than that in T0 in group S. Other inflammatory factors including IL-4, IL-6, TNF-a and INF-y did not show significant changes after using oxycodone or sufentanil for PCIA.

Postoperative pain is a common perioperative complication that can have adverse effects on the patients, including atelectasis, pulmonary embolism, and sleep disorders [20]. It is important to choose appropriate analgesics for different types of pain [21]. For example, NSAID drugs can be used for inflammatory pain, opioids can be used for incision pain and visceral pain can be treated with oxycodone, while neuropathic pain can be treated with gabapentin or pregabalin. Oxycodone, a unique dual receptor agonist, has outstanding effects in reducing visceral pain on different types of surgeries, including laparoscopic surgery[22], laparotomy[23], thoracic surgery [24],and painless endoscopy operation[25]. Recent research has found that patients with oxycodone for postoperative analgesia had lower numerical rating scale (NRS) of visceral pain at 2 h and 4 h after laparoscopic cholecystectomy surgery compared to the sufentanil group [10]. In our study, we have found that oxycodone can significantly reduce pain, particularly in cancer patients, where it has been shown to improve pain management outcomes. visceral pains in patients at 24 h and 72 h after elective laparoscopic resection of CRC compared to sufentanil, which was consistent with the results of the previous study [10]. Peripheral κ-opioid receptors are considered as a potential target for reducing visceral pain [26]. Compared to sufentanil, oxycodone has a stronger affinity for peripheral κ-opioid receptors, so its inhibitory effect on visceral pain is significant. Oxycodone increases the threshold of visceral pain stimulation [27], thereby blocking peripheral pain signals and weakening the input of the central nervous system [26]. Numerous studies have shown that oxycodone can alleviate inflammatory reactions after surgery such as IL-6, TNF-α and IL-1β, which may be related to reducing visceral pain [11, 12]. Inflammatory mediators such as cytokines and prostaglandins can cause pain by stimulating visceral sensory nerves. In addition, inflammation can cause swelling, congestion, and spasms in internal organs, which can stimulate nerves, and then leading to pain [10].

T cells mainly mediate cellular immunity, while B cells mainly mediate humoral immunity. According to the different differentiation antigens on the cell surface, T cells can be divided into two subgroups: CD4+and CD8+ [15]. And B cells produce antibodies after receiving antigen stimulation. Both B cells and T cells express opioid receptors on their surfaces, and opioid drugs can bind to these receptors, affecting T cell differentiation and inhibiting B cell function. Many studies have revealed that opioid drugs have inhibitory effects on immune function [28] such as fentanyl, sufentanil, and morphine. On one hand, due to the impact of surgery and anesthesia on immune function, the use of opioid drugs during the perioperative period will further increase the risk of immune suppression [29]. On the other hand, opioid-induced immunosuppression has negative impact on the development of tumor [30]. Due to the specific molecular structure, the immunosuppressive function of oxycodone is limited [13]. Wan et al. revealed that administering oxycodone combined with flurbiprofen axetil as postoperative analgesia for CRC patients can reverse the status of immunosuppression [16]. Compared to pre injection, NK cells showed a decreasing trend at 0.5-, 6-, 12-, and 24-h after using oxycodone, but the rate of decrease was slower than that of the morphine group [15]. Wodehouse et al. evaluated the effects of morphine and oxycodone on the immune function of patients undergoing gynecological laparotomy, and proved that the activity of NK cells was suppressed by morphine, but maintained by oxycodone [14]. Recently, Chen et al. demonstrated that repeated intraperitoneal injections of oxycodone exceeding 20 mg/kg lead to a dose-dependent decrease in the count of CD4+ T cells, with little effect on CD8+ T cells [31]. In our study, we found that the serum lgG concentration at T1 was lower than that at T0 in Group O, and the serum lgG concentration in Group O was higher than that in Group S at 72 h after the surgery. Besides, the serum concentration of IL-2 in group O was higher than that in group S at T2. Other immune indicators including C3, C4, IgA, IgE, IgM, CD3+, CD4+, CD8+ and CD4+/CD8+ did not show significant changes after using oxycodone or sufentanil for PCIA. Undoubtedly, the immunosuppression may result in the enhancement of differentiation, metastasis and proliferation for tumor cells. This is very detrimental to cancer patients. Besides, cellular immune activity will be inhibited by all anesthesia methods. Hence, taking appropriate measures to develop individualized anesthesia and analgesia schemes is of great significance for protecting the perioperative immune function of cancer patients and improving their prognosis. IgG is the main component of immunoglobulin in serum, accounting for approximately 75% of immunoglobulin in serum. IgG is the most important antibody with functions of antiviral, neutralizing viruses, antibacterial, and immune regulation. The present results suggested that the serum lgG concentration in Group O was higher than that in Group S at 72 h after the surgery, which means that oxycodone may help to decrease the degree of immunosuppression compared to sufentanil. Moreover, IL-2 is an immunomodulator, which has antiviral, antitumor and immune enhancement effects. It can enhance the proliferation and killing activity of Cytotoxic T cells, natural killer cell and lymphokine activated killer cells, and can also promote the secretion of antibodies and interferon by lymphocytes. The results that oxycodone can promote the serum concentration of IL-2 at 72 h after the surgery but not sufentanil suggested it has a weakened immunosuppressive effect. However, we found that after using oxycodone for 24 h, the serum concentration of IgG decreased, which may be related to detection errors. In future clinical practice, using oxycodone as a postoperative intravenous analgesic can alleviate immune suppression, reduce the recurrence of disease and mortality rates, and shorten hospitalization time.

Currently, many articles have confirmed that oxycodone can alleviate inflammatory reactions [10, 12, 16, 32]. An and coworkers found that pre administration of oxycodone can alleviate inflammatory markers for forty patients undergoing laparoscopic cholecystectomy in 2019 [10]. Oxycodone combined with flurbiprofen axetil can reduce the serum level of TNF-α and IL-6 at 12-, 24-, 48-, and 72-h post-surgery in 2021 by wan and coworkers [16]. For patients undergoing laparoscopic resection surgery, oxycodone also has the effect of reducing inflammatory response [12]. In addition, oxycodone induced less inflammatory responses in patients undergoing laparoscopic gallbladder-preserving cholecystolithotomy compared with sufentanil [32]. However, Wang and coworkers found oral oxycodone can upregulate the levels of IL-2, IL-4, IL-6, IL-10, TNF-a, and IFN-y in patients with moderate to severe cancer pain [33]. In our study, we found that the IL-10 concentration in T1 was higher than that in T0 in group S. Other inflammatory factors including IL-4, IL-6, TNF-a and INF-y did not show significant changes after using oxycodone or sufentanil for PCIA. IL-10, an anti-inflammatory cytokine, can downregulate T lymphocyte activity and inhibit the activation, migration and adhesion of inflammatory cells. At the same time, IL-10 can also inhibit the synthesis and release of inflammatory factors. Our experimental results showed that the serum concentration of IL-10 increased with the use of sufentanil as PCIA for 24 h, which demonstrated that sufentanil has anti-inflammatory effects compared to oxycodone. The result was contrary to many current studies [10, 12, 16, 32]. More data is needed to prove this conclusion due to the small sample.

Different routes of administration of opioid drugs can have an impact on immune function. Beilin and coworkers revealed that immune suppression still existed in the PCIA group with morphine at 72 h after surgery, but the immune function of the PCEA group with morphine had recovered to preoperative levels [34]. Besides, Chen and coworkers found that oxycodone can inhibit immune function by intraperitoneal injection in mice [31]. In our experiment, we used sufentanil for anesthesia induction in Group O, which may increase the possibility of immune suppression. Due to the binding of opioid receptors on immune cells, sufentanil inhibits T cell differentiation and B cell function, thereby suppressing immune function. The operative method, such as the extent of lesion resection, the location of the lesion, and the method of residual treatment, also have an impact on immune function.

According to our experimental results, oxycodone has a good analgesic effect on postoperative visceral pain in patients undergoing laparoscopic resection of CRC. Oxycodone has no significant effect on inflammation and immune function. Therefore, the use of oxycodone as postoperative analgesia can achieve more satisfactory results for surgeries with significant visceral pain, such as gastrointestinal surgery, gynecological surgery, and urological surgery. Combining with nonsteroidal anti-inflammatory drugs will achieve more satisfactory analgesic effects [16]. In this study, we found that the incidence of side effects (nausea and vomiting) was higher when oxycodone was at the same potency as sufentanil. Therefore, in this study, the postoperative analgesia rate of oxycodone was 1 mg/h, which achieved good analgesic effect and the lowest incidence of complications. In conclusions, we provide more evidence about the application of oxycodone in laparoscopic resection of CRC for the Chinese population to perform postoperative analgesia.

The limitations of our study are as follow. Firstly, the data of our study is relatively small, and the variability of the data may be significant, making it impossible to statistically evaluate the significance of the experimental results. Secondly, complete blinding should be implemented between data analysts and anesthesiologists to ensure that the data is more objective and reliable. Thirdly, the observation cut-off point for this study is 72 h after surgery, and postoperative follow-up should continue to record the patient's discharge time and postoperative tumor recurrence rate. Besides, in addition to recording the patient's immune and inflammatory indicators, postoperative sleep status and the occurrence of adverse reactions can also be recorded.