Abstract: Melatonin influences arterial biomechanics, and its absence could cause remodeling of the arterial wall, leading to increased stiffness. Direct effects of fentanyl on the aortic wall have also been observed previously. This study aimed to evaluate in vitro the effects of fentanyl on aortic viscoelasticity in a rat model of melatonin deficiency. It also aimed to test the hypothesis that melatonin deficiency leads to increased arterial wall stiffness. The viscoelasticity of the aortic wall was estimated in strip preparations from pinealectomised and sham-operated adult rats using the forced oscillations method. We found that melatonin deficiency in the untreated aortic wall did not significantly alter viscoelasticity. However, combined with 10^-9 M fentanyl, melatonin deficiency increased the natural frequency and arterial stiffness compared to the sham-operated. Independently, fentanyl treatment decreased the natural frequency and arterial stiffness compared separately to untreated normal and melatonin-deficient preparations. The observed effects of fentanyl were neither dose-dependent nor affected by naloxone, suggesting a non-opioid mechanism. Furthermore, an independent effect of naloxone was also detected in the normal rat aortic wall, resulting in reduced arterial stiffness. Further studies are needed to clarify the underlying mechanisms, which may improve the clinical decisions for pain management and anesthesia.

Background and aims: For many surgical procedures, spinal anesthesia is a reliable and efficient anesthetic approach. Numerous drugs have been reported to be administered to intrathecal local anesthetics as adjuvants to increase the efficacy of spinal anesthesia. There is little evidence of the effect of intrathecal dexmedetomidine on pain scores and the consumption of analgesia postoperatively. Methods: After obtaining ethical approval, demographical and clinical data of patients who underwent surgical procedures under spinal anesthesia with intrathecal dexmedetomidine or fentanyl was collected and analyzed. Results: In this study with 96 patients, intrathecal dexmedetomidine (group D) resulted in significantly lower post-operative pain scores compared to intrathecal fentanyl (group F) (p=0.000). Across various surgical types, including Orthopedic, General, Urology, and Obs/Gyne procedures, group D consistently displayed reduced pain scores (p<0.001). The number of patients who needed post-operative analgesia was significantly higher in group (F) than in group (D) (40 vs 23, p=0.002). Conclusion: Compared to fentanyl, intrathecal dexmedetomidine as an adjuvant to local anesthesia was found to lower post-operative pain scores and decrease the need for post-operative analgesia.

The illicit use of fentanyl has led to hundreds of thousands of opioid-related deaths worldwide. Therefore, the detection of fentanyl by law enforcement and recreational users is of utmost importance. However, current detection methods are expensive, time-consuming, require special storage conditions and necessitate complex instrumentation that is generally unportable and requires skilled personnel to operate. An alternative approach would be using molecularly imprinted polymers (MIPs) as the recognition component of a handheld sensor, testing strip, or color-based assay. In this work, a molecularly imprinted polymer was made by using methacrylic acid (MAA) and ethyleneglycol dimethacrylate (EGDMA) as the functional monomer and cross-linking monomer respectively, and benzylfentanyl (Bfen) as the template. The use of benzylfentanyl is advantageous because it closely resembles the structure of fentanyl but does not have any physiological effects as a narcotic. Important studies herein determined the optimum ratio of the template:functional monomer, with subsequent evaluations of selectivity versus the commonly encountered narcotics such as heroin, cocaine, and methamphetamine. The data obtained from the HPLC analysis showed that the Bfen-MIP was successful in selectively binding the template and actual fentanyl, better than other common narcotics.

Objectives: To explore the effect of breakthrough cancer pain (BTcP) treatment on quality of sleep and other aspects of the health-related quality of life (HRQoL) in patients with cancer pain. Methods: In an observational, multicenter, cohort study, cancer patients from palliative care units, oncology departments, and pain clinics and affected by BTcP were included. Enrolled patients were assessed at the four visits: T0 (baseline), T7, T14, and T28. Well-controlled chronic background pain during the whole study period was mandatory. BTcP was treated through transmucosal fentanyl. Three questionnaires were used to measure the HRQoL: EORTC QLQ-C15-PAL, Pittsburgh Sleep Quality Index (PSQI), and the Edmonton Symptom Assessment System (ESAS). Results: In 154 patients, the HRQoL showed a significant improvement for all physical and emotional characteristics in the EORTC QLQ-C15-PAL, except for nausea and vomiting (Linear p-value = 0.1) and dyspnoea (Linear p-value =0.05). The ESAS and PSQI questionnaires confirmed these positive results (p<0.0001 and p=0.002, respectively). Conclusions: This prospective investigation by an Italian expert group, has confirmed that careful management of BTcP induces a paramount improvement on the HRQoL. Because in cancer patients there is a high prevalence of BTcP and this severe acute pain has deleterious consequences, this information can have an important clinical significance

In the Emergency Department (ED), pain is one of the symptoms that is most frequently reported, making it one of the most significant issues for the emergency physician, but is frequently under treated. Intravenous (IV), oral (PO), and intramuscular (IM) delivery are the standard methods for administering acute pain relief. Firstly, we compared the safety and efficacy of IN analgesia to other conventional routes of analgesia to assess if IN analgesia may be an alternative for the management of acute pain in ED. Secondary, we analyzed the incidence and severity of adverse events (AEs) and rescue analgesia required. We performed a systematic review-based keywords in Pubmed/Medline, Scopus, EMBASE, the Cochrane Library and Controlled Trials Register finding only twenty randomized Clinical trials eligible in the timeline 1992-2022. A total of 2098 patients were analyzed and compared to intravenous analgesia showing no statistical difference in adverse effects. In addition, intranasal analgesia also has a rapid onset and quick absorption. Fentanyl and ketamine are two intranasal drugs that appear promising and may be taken simply and safely while providing effective pain relief. IN is simple to administer, non-invasive, rapid onset and quick absorption; it might be a viable choice in a variety of situations to reduce patient suffering or delays in pain management. Analgesia needs to be tailored to each patient's features and type of pain: IN Fentanyl and Ketamine look promising and may be administered easily and safely while providing effective pain relief.