Patients with FF often undergo surgical treatment, which frequently leads to a high incidence of postoperative pain. This not only increases perioperative risks but also affects patient prognosis [10, 11]. Sufentanil, a thiophene derivative of fentanyl, is known for its ability to easily cross the blood-brain barrier and has a long duration of action. It rapidly reaches peak drug concentration [12, 13], and is commonly used as a postoperative analgesic in clinical practice. However, high-dose administration can result in various adverse reactions, including excessive sedation, dizziness, gastrointestinal dysfunction, severe respiratory suppression, and even death [14]. Studies have shown significant individual differences in the efficacy of sufentanil due to various factors, such as genetic variation and socio-cultural influences. Genetic variation, particularly single nucleotide polymorphisms (SNPs), plays a major role in this context [15]. However, research on the genetic variation related to opioid drugs has focused mainly on fentanyl and morphine, there are limited reports on sufentanil. One extensively studied gene locus is C1236T within the ABCB1 gene, located on chromosome 7. The majority of studies indicate that this locus is closely associated with P-gp activity [16]. Some researchers believe that mutations in the ABCB1C1236T gene affect the excretion of opioid drugs from central nervous system tissues, resulting in variations in drug concentration and individualized differences in drug efficacy [17]. Our study demonstrated that when the C allele mutates to T, patients would experience increased pain scores, suggesting that the C1236T gene polymorphism may be one of the genetic factors influencing the postoperative analgesic effect of sufentanil.
The ABCB1 gene encodes P-gp, which exhibits high polymorphism [18]. Over 50 SNPs have been identified within its coding region. C1236T is the most common synonymous mutation and has been shown to impact the transport capacity of P-gp for substrates [19]. Synonymous mutations refer to changes in the codon on messenger RNA, which result in an unaltered sequence of amino acid connections in the precursor protein formed during gene transcription. However, these changes affect the conformational folding of the corresponding amino acid and protein precursor during RNA transport, ultimately leading to conformational changes in P-gp. Our results indicated that, in the non-morphine group, patients with the CC genotype had lower postoperative NRS scores on the first day). However, no statistically significant differences were observed regarding postoperative pain onset time, PCA compression frequency, PCA pump dosage, and postoperative nausea and vomiting on days 2, 3, and 7 (P > 0.05). These findings suggest that C1236T may affect the early postoperative analgesic effect of sufentanil. After the C allele mutates to T, intracellular sufentanil becomes difficult to excrete from the cell, resulting in a weakened analgesic effect.
With the development of multimodal analgesia techniques, intravenous analgesia pumps alone can no longer fully meet the postoperative pain relief requirements of patients. A meta-analysis reveals that epidural analgesia yields similar analgesic effects to continuous wound infiltration, continuous paravertebral block, and intrathecal injection of morphine. There are no statistical differences in postoperative adverse reactions and hospital stay [20]. Moreover, epidural use is a simple and easily implementable approach. Morphine, the most commonly employed epidural drug, achieves analgesia by activating opioid receptors [21]. However, the dose-response relationship for analgesia varies greatly among individuals, and the absorption and transport of proteins and catalytic metabolic enzymes influence the analgesic effect of morphine from a pharmacokinetic perspective [22]. Studies by Gustafsson et al. [23] indicated that patients receiving a single epidural injection of morphine (0.05 mg/kg) experienced a significant decrease in pain scores, and they were able to move their knee joints 2–3 hours after surgery. Additionally, a systematic review and meta-analysis by Bonnet et al.[24] demonstrated that the epidural morphine group had low pain scores within the first 24 hours postoperatively. Singh et al. [25] found no significant difference in postoperative analgesic effects between epidural morphine injections of 1.5mg and 3mg, but observed a low incidence of skin itching. In our study, patients in the morphine group received a postoperative epidural injection of 1.5mg of morphine. The results revealed that compared to patients in the non-morphine group, those in the morphine group experienced a longer onset of postoperative pain (P < 0.05). Within the morphine group, there were no statistically significant differences (P > 0.05) among the three genotypes in terms of postoperative NRS, postoperative pain onset time, PCA compression frequency, PCA pump dosage, and postoperative nausea and vomiting. This may be attributed to the C1236T gene mutation reducing the efflux of morphine from the central nervous system and enhancing its short-term analgesic effect, which aligns with the research findings of Sia et al. [26]. Therefore, epidural use of morphine can mitigate individual differences caused by C1236T gene polymorphism in early sufentanil analgesia.
A multiple linear regression analysis was performed, with postoperative 1-day NNRS scores as the dependent variable. The results indicated a significant association between postoperative 1-day NRS scores, pain onset time, and the ABCB1C1236T genotype (P < 0.05). These findings suggest that the C1236T genotype may be one of the genetic factors influencing early postoperative pain in patients with FF. Mutations in the C1236T gene could potentially affect the excretion of sufentanil in the nervous system, leading to changes in its concentration and resulting in individual variation in efficacy. It is also possible that P-gp activity influences the concentration of sufentanil in the nervous system, and gene mutations may alter P-gp activity and its ability to efflux sufentanil, consequently affecting its analgesic effect.