Apigenin Alleviates Allodynia and Hyperalgesia in a Mouse Model of Chemotherapy-Induced Peripheral Neuropathy via Regulating Microglia Activation and Polarization.

BACKGROUND: Apigenin has been reported to exhibit anti-inflammatory and anti-oxidative activities. This study aimed to investigate the protective role of Apigenin on chemotherapy-induced peripheral neuropathy (CIPN). METHODS: CIPN mouse model was established using Paclitaxel treatment. Hot plate and tail prick latency tests were performed to examine the allodynia and hyperalgesia behaviors. Anti-inflammatory and anti-oxidative effects of Apigenin on CIPN were determined by enzyme-linked immunosorbent (ELISA) assay, Western blot, and qRT-PCR. Nuclear recruitment of nuclear factor erythroid 2-related factor 2 (NRF2) was analyzed to evaluate the underlying mechanisms of the protective effects of Apigenin. RESULTS: Apigenin significantly alleviated CIPN-induced nociceptive behaviors of CIPN mice. It also decreased the TNF-α and IL-1ß levels, suppressed oxidative stress and inflammation in the surgical spinal cord tissues. Mechanistically, Apigenin altered the pro-inflammatory and anti-inflammatory phenotypes ratio of microglia through promoting the nuclear recruitment of NRF2 and activating the NRF2/Antioxidant Response Element (ARE) signaling pathway. CONCLUSIONS: In summary, Apigenin relieves CIPN by regulating microglia activation and polarization, which provides a potential therapeutic strategy for CIPN treatment.

Nalbuphine Exhibited a Better Adjuvant Than Dexmedetomidine in Supraclavicular Brachial Plexus Block in Youths.

OBJECTIVE: Nalbuphine and dexmedetomidine are both used as anesthesia adjuvants for brachial plexus block, but their efficacy and safety in younger patients are not clear. In this study, we aimed to compare the efficacy and side effects of these 2 drugs in young patients undergoing brachial plexus block. METHODS: We recruited 48 young patients aged 18 to 30 years requiring supraclavicular brachial plexus block. Subjects were randomly divided into 2 groups. Patients in group levobupivacaine+nalbuphine received 28 mL of 0.5% levobupivacaine and 10 mg of nalbuphine diluted in 2 mL 0.9% saline. Patients in group levobupivacaine+dexmedetomidine (LD) received 28 mL of 0.5% levobupivacaine and 0.75 µg/kg dexmedetomidine diluted in 2 mL 0.9% saline. Demographic information, types of fracture, onset time of motor and sensory blocks, duration of block, side effects, and analgesic use were recorded. RESULTS: We found that the 2 groups did not differ significantly in the demographic profile and fracture type. Compared with group LD, group LD had significantly shorter sensory and motor block onset time, longer block duration, less analgesic need, and less side effects. CONCLUSION: In summary, our study suggests that nalbuphine is a better anesthesia adjuvant for supraclavicular brachial plexus block in young patients.

Administration of Curcumin Alleviates Neuropathic Pain in a Rat Model of Brachial Plexus Avulsion.

BACKGROUND/AIMS: Brachial plexus avulsion (BPA) generally causes a chronic persistent pain that lacks efficacious treatment. Curcumin has been found to possess anti-inflammatory abilities. However, little is known about the mechanisms and effects of curcumin in an animal model of BPA. METHODS: Mechanical withdrawal thresholds (MWT) were examined by von Frey filaments. Cold allodynia was tested by the acetone spray test. The levels of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in rat spinal cords were analyzed by the enzyme-linked immunosorbent assay, and the expression levels of c-Fos and nerve growth factor (NGF) were measured by Western blot. The expression level of glial fibrillary acidic protein (GFAP) was observed by immunofluorescence and Western blot. RESULTS: After curcumin treatment, the MWT showed a significant increase when compared to the BPA group on both hind paws. A remarkable decrease of paw-withdrawal response frequency was observed compared with the BPA group. In addition, curcumin treatment significantly decreased the levels of TNF-α and IL-6 in rat spinal cords that were exceedingly upregulated in the BPA group. The protein levels of c-Fos and NGF were decreased by treatment with curcumin compared with the corresponding protein levels in the BPA group. Besides, curcumin reduced the number of GFAP positive cells and GFAP expression. CONCLUSIONS: Our findings suggest that curcumin significantly extenuates the BPA-induced pain and inflammation by reducing the expression level of proinflammatory cytokines and pain-associated proteins and inhibiting the activity of astrocytes.

Hydromorphone protects CA1 neurons by activating mTOR pathway.

Hydromorphone has been shown to play protective effect in rat glial cell. However, whether hydromorphone plays important roles in ischemia-reperfusion (IR) injury and the involved signaling pathway remains unclear. In this study, we detected whether HM plays protective effect in IR injury mouse model, further followed by the mechanism exploration. Preconditioning with hydromorphone was performed for continuous 4 days at the doe of 2 mg/kg before IR injury induction. Intraperitoneal injection of rapamycin (Rapa) was administrated to examine the role of mTOR in IR injury. The mRNA expression level was detected by RT-PCR, and protein expression level was detected by western blot. Latency time and apoptosis of hippocampal CA1 neurons were detected 72 h after IR injury induction. Preconditioning with hydromorphone significantly increased Latency time, decreased apoptosis of hippocampal CA1 neurons and suppressed IR induced oxidative stress. Mechanically, preconditioning with hydromorphone increased Bcl-2 and p-mTOR expression levels and decreased Bax expression levels. Rapa administration reverses the role of hydromorphone in protecting hippocampal CA1 neurons from IR injury. Hydromorphone protect hippocampal CA1 neurons from IR injury via activating mTOR signaling pathway.

Apigenin attenuates isoflurane-induced cognitive dysfunction via epigenetic regulation and neuroinflammation in aged rats.

PURPOSE OF THE RESEARCH: Post operational cognitive dysfunction (POCD) occurs in patients after anesthesia and surgery. Abnormal histone acetylation and neuroinflammation are key factors in the pathogenesis of cognitive impairment. Apigenin not only has an anti-inflammatory activity but also modifies histone acetylation. We aimed to investigate whether apigenin can attenuate isoflurane exposure-induced cognitive decline by regulating histone acetylation and inflammatory signaling. MATERIALS AND METHODS: Spatial learning and memory were assessed by Morris water maze test. Levels of histone acetylation, BDNF and downstream signaling, and inflammatory components were analyzed. PRINCIPAL RESULTS: Isoflurane exposure in aged rats lead to impaired spatial learning and memory. These rats exhibited dysregulated histone H3K9 and H4K12 acetylation, which was accompanied by reduced BDNF expression and suppressed BDNF downstream signaling pathway. Apigenin restored histone acetylation and BDNF signaling. Apigenin also suppressed isoflurane exposure induced upregulation of proinflammatory cytokines and NFκB signaling pathway. MAJOR CONCLUSIONS: Memory impairment induced by isoflurane exposure is associated with dysregulated histone acetylation in the hippocampus, which affects BDNF expression and hence BDNF downstream signaling pathway. Apigenin recovers cognitive function by restoring histone acetylation and suppressing neuroinflammation.