Caffeic acid phenethyl ester attenuates neuropathic pain by suppressing the p38/NF-κB signal pathway in microglia.

BACKGROUND: Management of neuropathic pain is still a clinical challenge. Evidence has accumulated indicating that propolis is effective in attenuating neuropathic pain; however, the mechanism is not fully understood. Our present study investigated the effects and the possible mechanism of caffeic acid phenethyl ester (CAPE), the main ingredient of propolis, in improving neuropathic pain via its inhibition on p38/NF-κB signal pathway in microglia. MATERIALS AND METHODS: Chronic constriction injury (CCI) mice model and the microglial cell line BV-2 were used to investigate the effects and the mechanism of CAPE. Cell signaling was measured by real-time PCR, Western blotting and immunofluorescence assay. RESULTS: CAPE relieved neuropathic pain behaviors induced by CCI in mice. CAPE also inhibited CCI-induced activation of microglia. Furthermore, CAPE suppressed the phosphorylation of p38 mitogen-activated protein kinase, inhibited the translocation of NF-κB and decreased the expression of proinflammatory cytokines tumor necrosis factor-α, IL-1ß and IL-6. CONCLUSION: CAPE was found to be an effective and safe drug candidate for alleviating neuropathic pain by its powerful inhibition on the P38/NF-κB signal pathway.

Network meta-analysis of percutaneous vertebroplasty, percutaneous kyphoplasty, nerve block, and conservative treatment for nonsurgery options of acute/subacute and chronic osteoporotic vertebral compression fractures (OVCFs) in short-term and long-term effects.

BACKGROUND: Osteoporotic vertebral compression fractures (OVCFs) commonly afflicts most aged people resulting back pain, substantial vertebral deformity, functional disability, decreased quality of life, and increased adjacent spinal fractures and mortality. Percutaneous vertebral augmentation (PVA) included percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP), nerve block (NB), and conservative treatment (CT) are used for the nonsurgery treatment strategy of OVCFs, however, current evaluation of their efficacy remains controversial. METHODS AND ANALYSIS: A systematic literature search was carried out in PubMed, EMBASE, Web of Knowledge, and the Cochrane Central Register of Controlled Trials up to October 31, 2017. Randomized controlled trials (RCTs) were compared PVP, PKP, NB, or CT for treating OVCFs. The risk of bias for each trial was rated according to the Cochrane Handbook. Mean differences (MDs) with 95% confidence intervals (CIs) were utilized to express VAS (visual analog scale) outcomes. The network meta-analysis (NMA) of the comparative efficacy measured by change of VAS on acute/subacute and chronic OVCFs was conducted for a short-term (<4 weeks) and long-term (≥6-12months) follow-up with the ADDIS software. RESULTS: A total of 18 trials among 1994 patients were included in the NMA. The PVA (PVP and PKP) had better efficacy than CT. PKP was first option in alleviating pain in the case of the acute/subacute OVCFs for long term, and chronic OVCFs for short term and long term, while PVP had the most superiority in the case of the acute/subacute OVCFs for short term. NB ranks higher probability than PKP and PVP on acute/subacute OVCFs in short and long-term, respectively. CONCLUSIONS: The present results suggest that PVA (PVP/PKP) had better performance than CT in alleviating acute/subacute and chronic OVCFs pain for short and long-term. NB may be used as an alternative or before PVA, as far as pain relief is concerned. Various nonsurgery treatments including CT, PVA (PVP/PKP), NB, or a combination of these treatments are performed with the goal of reducing pain, stabilizing the vertebrae, and restoring mobility.

Effect of intrathecal dexmedetomidine on spinal morphine analgesia in patients with refractory cancer pain.

BACKGROUND: Systemic administration of dexmedetomidine has been shown to reduce opioid consumption and improve analgesia satisfaction. The purpose of this study was to investigate the effect of intrathecal dexmedetomidine on spinal morphine analgesia in patients with refractory cancer pain. METHODS: A double-blinded crossover study was designed and performed. Patients were randomly allocated in one of the two phases. Phase M received intrathecal morphine administration. Phase M+D received intrathecal morphine plus dexmedetomidine administration. All patients were monitored for 7 days and crossed over to alternate phase for another 1-week observation. Daily average visual analog scale (VAS) pain score, pain frequency, sleep deprivation, daily morphine consumption, bolus dose injection times, and side effects were all recorded. RESULTS: Pain intensity and frequency were significantly decreased in both phases compared with baseline. Daily morphine consumption and bolus dose injection times during phase M+D were significantly decreased compared with phase M. The incidences of constipation were significantly reduced in both phases compared with baseline administration, but nausea and vomiting were significantly increased. No serious side effects such as respiratory inhibition were observed in this study. CONCLUSIONS: Intrathecal administration of dexmedetomidine and morphine reduced the morphine consumption in patients with refractory cancer pain. There were no serious side effects.