Bone cancer pain (BCP) is excruciating for cancer patients, with limited clinical treatment options and significant side effects, due to the complex and unclear pathogenesis of bone cancer pain. Peripheral sensitization in dorsal root ganglion (DRG) neurons is a recognized cellular mechanism for bone cancer pain. The pathological mechanism of chronic pain is increasingly being affected by epigenetic mechanisms. In this study, we unbiasedly showed that the DNA hydroxymethylase ten-eleven translocation 1 (TET1) expression was significantly increased in the L4–6 DRG of BCP rats and ten-eleven translocation 2 (TET2) expression did not change significantly. Notably, TET1 inhibition by intrathecal injection of Bobcat339 (a TET1 inhibitor) effectively relieved mechanical hyperalgesia in BCP rats. Peripheral sensitization in chronic pain relies on the activation and overexpression of ion channels on neurons. Here, we demonstrated that TRPV4, one of the transient receptor potential ion channel family members, was significantly elevated in the L4–6 DRG of BCP rats. In addition, TRPV4 inhibition by intrathecal injection of HC067047 (a TRPV4 inhibitor) also significantly attenuated mechanical hyperalgesia in BCP rats. Interestingly, we found that TET1 inhibition downregulated TRPV4 expression in the L4–6 DRG of BCP rats. As a result, these findings suggested that TET1 may contribute to bone cancer pain by upregulating TRPV4 expression in the L4–6 DRG of BCP rats and that TET1 or TRPV4 may become therapeutic targets for bone cancer pain.

Chronic inflammatory pain is the highest priority for people with osteoarthritis when seeking medical attention. Despite the availability of NSAIDs and glucocorticoids, central sensitization and peripheral sensitization make pain increasingly difficult to control. Previous studies have identified the ubiquitination system as an important role in the chronic inflammatory pain. Our study displayed that the E3 ubiquitin ligase tripartite motif-containing 14 (Trim14) was abnormally elevated in the serum of patients with osteoarthritis and pain, and the degree of pain was positively correlated with the degree of Trim14 elevation. Furthermore, CFA-induced inflammatory pain rat model showed that Trim14 was significantly increased in the L3-5 spinal dorsal horn (SDH) and dorsal root ganglion (DRG), and in turn the inhibitor of nuclear factor Kappa-B isoform α (IκBα) was decreased after Trim14 elevation. After intrathecal injection of Trim14 siRNA to inhibit Trim14 expression, IκBα expression was reversed and increased, and the pain behaviors and anxiety behaviors of rats were significantly relieved. Overall, these findings suggested that Trim14 may contribute to chronic inflammatory pain by degrading IκBα, and that Trim14 may become a novel therapeutic target for chronic inflammatory pain.

Background and Aims: As gynaecological laparoscopic minimally invasive surgery continues to advance, it becomes essential to explore how inhalation anaesthesia and intravenous anaesthesia affect the recovery of gastrointestinal function after surgery. The objective was to compare the effects of total intravenous anaesthesia (TIVA) and inhalation anaesthesia on the time of the first defecation and the time of consuming solid food for patients following laparoscopic total hysterectomy. Methods: This research involved 134 female participants aged 18–65 years, classified as American Society of Anesthesiologists physical status I–II, who were scheduled to undergo elective laparoscopic hysterectomy procedures. Participants were randomly allocated into two cohorts: one receiving TIVA (Group P) (underwent TIVA induction with propofol, remifentanil, and rocuronium administration, supplemented by ongoing administration of propofol-remifentanil infusions), and the other group was administered inhalational anaesthesia (Group S) (using sevoflurane delivered through precise tidal volume ventilation alongside rocuronium, with maintenance achieved through combined sevoflurane inhalation and remifentanil infusion). The primary outcome was the time to initial defecation and tolerance of solid food (SF + D), while the final outcome was determined by the longer duration required to achieve these two outcomes. The I-FEED (intake, feeling nauseated, emesis, physical examination, and duration of symptoms) score, the numeric rating scale score for pain, and the numeric rating scale score for postoperative nausea and vomiting, the time to first flatus, gastric antral motility index, and intestinal peristalsis rate within 1 minute determined by bedside ultrasound were also recorded. Results: The mean to first defecation + hard food tolerance (SF + D) was 51 [standard deviation (SD: 8.47)] in Group S and 47 (SD: 9.45) in Group P ( P = 0.02), and the mean difference between the groups was − 4.46 (95% CI: 0.20, 7.00). None of the I-FEED scores were statistically significant ( P = 0.074, Z = −1.79). Patients in Group P experienced superior analgesic effects and more stable haemodynamics. Conclusion: The postoperative recovery of gastrointestinal function can be enhanced by employing total intravenous anaesthesia instead of inhalation anaesthesia.