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Decursinol-mediated antinociception and anti-allodynia in acute and neuropathic pain models in male mice: Tolerance and receptor profiling.

Korean scientists have shown that oral administration of Nakai (AGN) root alcoholic extract and the metabolite of its pyranocoumarins, decursinol, have antinociceptive properties across various thermal and acute inflammatory pain models. The objectives of this study were 1) to assess whether tolerance develops to the antinociceptive effects of once-daily intraperitoneally administered decursinol (50 mg/kg) in acute thermal pain models, 2) to establish its anti-allodynic efficacy and potential tolerance development in a model of chemotherapy-evoked neuropathic pain (CENP) and 3) to probe the involvement of select receptors in mediating the pain-relieving effects with antagonists. The results show that decursinol induced antinociception in both the hot plate and tail-flick assays and reversed mechanical allodynia in mice with cisplatin-evoked neuropathic pain. Tolerance was detected to the antinociceptive effects of decursinol in the hot plate and tail-flick assays and to the anti-allodynic effects of decursinol in neuropathic mice. Pretreatment with either the 5-HT antagonist methysergide, the 5-HT antagonist volinanserin, or the 5-HT antagonist SB-242084 failed to attenuate decursinol-induced antinociception in the tail-flick assay. While pretreatment with the cannabinoid inverse agonists rimonabant and SR144528 failed to modify decursinol-induced anti-allodynia, pretreatment with the opioid antagonist naloxone partially attenuated the anti-allodynic effects of decursinol. In conclusion, our data support decursinol as an active phytochemical of AGN having both antinociceptive and anti-allodynic properties. Future work warrants a more critical investigation of potential receptor mechanisms as they are likely more complicated than initially reported.

Evidence basis for using dexmedetomidine to enhance the quality of paravertebral block: A systematic review and meta-analysis of randomized controlled trials.

Dexmedetomidine is considered an adjunct to local anaesthesia (LA) to prolong peripheral nerve block time. However, the results from a previous meta-analysis were not sufficient to support its use in paravertebral block (PVB). Therefore, we performed an updated meta-analysis to evaluate the efficacy of dexmedetomidine combined with LA in PVB. We performed an electronic database search from the date of establishment to April 2022. Randomized controlled trials (RCTs) investigating the combination of dexmedetomidine and LA compared with LA alone for PVB in adult patients were included. Postoperative pain scores, analgesic consumption, and adverse reactions were analyzed. We identified 12 trials (701 patients) and found that the application of dexmedetomidine as a PVB adjunct reduced the postoperative pain severity of patients 12 and 24 h after surgery compared to a control group. Expressed as mean difference (MD) (95% CI), the results were -1.03 (-1.18, -0.88) ( < 0.00001, I = 79%) for 12 h and -1.08 (-1.24, -0.92) ( < 0.00001, I = 72%) for 24 h. Dexmedetomidine prolonged the duration of analgesia by at least 173.27 min (115.61, 230.93) ( < 0.00001, I = 81%) and reduced postoperative oral morphine consumption by 18.01 mg (-22.10, 13.92) ( < 0.00001, I = 19%). We also found no statistically significant differences in hemodynamic complications between the two groups. According to the GRADE system, we found that the level of evidence for postoperative pain scores at 12 and 24 h was rated as moderate. Our study shows that dexmedetomidine as an adjunct to LA improves the postoperative pain severity of patients after surgery and prolongs the duration of analgesia in PVB without increasing the incidence of adverse effects.

Evaluation of preoperative duloxetine use for postoperative analgesia following laparoscopic cholecystectomy: A randomized controlled trial.

The pain pattern after laparoscopic cholecystectomy (LC) is complex and distinct from postoperative pain after other laparoscopic procedures, suggesting that procedure-specific optimal analgesic management plans should be proposed. Duloxetine, a non-opioid neuromodulator, has been widely used to manage pain with dual central and peripheral analgesic properties. To assess the effect of preoperative administration of duloxetine compared to placebo on postoperative pain control in patients undergoing LC. This study was a randomized, parallel-group, placebo-controlled, double-blinded study performed on patients undergoing LC. Patients were randomly divided into two groups of 30 each on the day of surgery in the preoperative holding area, using a computer-generated random number to receive 60 mg duloxetine as a single oral dose 2 h before the procedure or placebo. The primary outcome was the difference in the mean of visual analogue scale (VAS) scores between the two studied groups, as measured by the area under the curve (AUC) of the VAS scores. The derived AUC of VAS scores in the duloxetine group (757.89 ± 326.01 mm × h) was significantly lower than that calculated for the control group (1005.1 ± 432.5 mm × h). The mean postoperative VAS scores recorded at 4 and 24 h were statistically different between the study groups ( = 0.041 and 0.003, respectively). As observed in the survival curve analysis, there was no significant difference ( = 0.665) for the time until the patient's first request for rescue medications in the two groups. The frequency of postoperative nausea and vomiting (PONV) was lower in patients of the duloxetine group than that recorded in those allocated to the control group at 8 and 24-h time intervals ( = 0.734 and 0.572, respectively). Preoperative use of duloxetine reduces postoperative pain significantly compared with placebo. In addition, its use is associated with a reduction in PONV. These preliminary findings suggest that duloxetine could play a role in the acute preoperative period for patients undergoing LC. [https://clinicaltrials.gov/ct2/show/NCT05115123, identifier NCT05115123].

Validity and reliability of the Arabic version of the revised illness perception questionnaire for patients with hypertension.

Hypertension is one of the leading causes of morbidity and mortality in Saudi Arabia affecting 31.4% of the population. The Illness Perception Questionnaire-Revised (IPQ-R) is a validated and reliable tool for assessing the perception of hypertension among patients. This cross-sectional study aimed to translate the Revised Illness Perception Questionnaire (IPQ-R) into Arabic and validate it among Arabic patients with hypertension from the outpatient departments of the Prince Sattam University Hospital and King Khalid Hospital (KKH) in Al-Kharj City in the Kingdom of Saudi Arabia.

Transcriptomic and proteomic profiling of Na1.8-expressing mouse nociceptors.

Inhibition of angiogenetic macrophages reduces disc degeneration-associated pain.

Abnormal angiogenesis and innervation in avascular discs during lumbar disc degeneration (LDD) cause severe back pain. These pathological alterations in the degenerating discs are induced by cytokines partially produced and secreted by inflammatory cells, among which macrophages are the most frequently ones detected at the legion site. However, the role of macrophages as well as their polarization in regulation of innervation and angiogenesis in the degenerating discs is unclear. In this study, we analyzed macrophages in the degenerating discs from patients and detected a specific macrophage subtype that expresses high levels of vascular endothelial growth factor A (VEGF-A). Co-expression of M2 macrophage markers in this macrophage subtype suggested that they were a M2d-like subtype. High levels of VEGF-A and genes associated with angiogenesis were also detected in LDD specimens compared to control heathy discs from a public database, consistent with our finding. Moreover, the levels of VEGF-A in disc macrophages were strongly correlated to the pain score of the examined patients, but not to the Thompson classification of the degeneration level of the patients. , overexpressing VEGF-A in macrophages increased the tube formation, proliferation and migration of co-cultured endothelial cells, and increased the innervation of embryonic spinal cord explant into the co-cultured area for macrophages and skeletal myocytes. , an orthotopic injection of adeno-associated virus carrying siRNA for VEGF-A under a macrophage-specific CD68 promoter significantly reduced the number of VEGF-A-positive disc macrophages and alleviated the pain in LDD-mice. Together, these data suggest that inhibition of angiogenetic potential of macrophages may reduce disc degeneration-associated pain through suppression of angiogenesis and innervation, as a promising therapy for LDD-associated pain.

Comparison of transversus abdominis plane blocks with liposomal bupivacaine versus ropivacaine in open total abdominal hysterectomy.

Regional anesthesia is frequently employed in efforts to improve postoperative analgesia and reduce opioid requirements following abdominal surgery. The purpose of the current analysis was to determine if there was a difference in postoperative pain and opioid consumption between patients who underwent open total abdominal hysterectomy (TAH) and received ultrasound-guided bilateral transversus abdominis plane (TAP) blocks using either liposomal bupivacaine or ropivacaine. A single-center retrospective analysis was conducted of 215 patients from November 2018 through March 2020 who underwent an open TAH and received bilateral TAP blocks with either liposomal bupivacaine or ropivacaine. The primary outcome measure was opioid consumption at regular intervals until discharge, and the secondary outcome measures included pain scores, incidence of nausea/vomiting, and use of antiemetics at the same time intervals. Intraoperative opioid consumption and postanesthesia recovery unit opioid requirements were similar between the two groups. Opioid requirements at 24 hours ( < 0.04) and 48 hours ( < 0.01), as well as total morphine equivalent requirements ( < 0.05), were significantly lower in the liposomal bupivacaine group compared to the ropivacaine group. Patients undergoing open TAH who received liposomal bupivacaine TAP blocks required fewer postoperative opioids to achieve similar pain scores when compared to patients who received ropivacaine TAP blocks.

Dysphagia lusoria in a young woman with chest pain.

Patients with dysphagia often have an esophageal disorder. This case report describes a patient with persistent dysphagia and chest pain who had a normal esophagogastroduodenoscopy. Computed tomography of the chest with contrast revealed an aberrant right subclavian artery compressing the esophagus. A vascular procedure was performed and corrected the dysphagia. This case demonstrates that aberrant vessels can occasionally cause dysphagia.

The pros and cons of multiple puncture in percutaneous balloon compression for treatment of trigeminal neuralgia.

Percutaneous balloon compression (PBC) is an effective and well-established surgery for treating trigeminal neuralgia (TN). However, if the initial attempt fails to produce a distinct pear shape, there is no conventional strategy to follow: repeat a few days later or re-puncture?

Recurrent benign lymphocytic (Mollaret’s) meningitis due to herpes simplex virus type 2.

We present a rare case of Mollaret's meningitis in a young patient with seven prior episodes of recurrent meningitis. The patient presented with headache, fever, neck stiffness, nausea, and vomiting. Brain imaging revealed no acute abnormalities. Lumbar puncture revealed elevated nucleated cells with lymphocytic predominance. The patient was started on antimicrobials including acyclovir. Cerebrospinal fluid polymerase chain reaction was positive for herpes simplex virus type 2. Her 2-day hospital course was uncomplicated, and she was discharged in good condition. Mollaret's meningitis, also known as recurrent benign lymphocytic meningitis, is a rare clinical disorder characterized by at least three recurrent episodes of meningitis associated with spontaneous recovery with or without antiviral therapy. Herpes simplex virus type 2 has frequently been implicated in the setting of this illness.

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