Mol Pain
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Our previous study reported the translocator protein to play a critical role in neuropathic pain and the possible mechanisms in the spinal cord. However, its mechanism in the peripheral nervous system is poorly understood. This study was undertaken to explore the distribution of translocator protein in the dorsal root ganglion and the possible mechanisms in peripheral nervous system in a rat model of spared nerve injury. ⋯ Our results suggested Ro5-4864 could alleviate neuropathic pain and attenuate p-ERK and brain-derived neurotrophic factor activation in dorsal root ganglion. Furthermore, Ro5-4864 stimulated the expression of myelin regeneration proteins which may also be an important factor against neuropathic pain development. Translocator protein may present a novel target for the treatment of neuropathic pain both in the central and peripheral nervous systems.
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Cancer-induced bone pain is one of the most severe types of pathological pain, which often occurs in patients with advanced prostate, breast, and lung cancer. It is of great significance to improve the therapies of cancer-induced bone pain due to the opioids' side effects including addiction, sedation, pruritus, and vomiting. Sinomenine, a traditional Chinese medicine, showed obvious analgesic effects on a rat model of chronic inflammatory pain, but has never been proven to treat cancer-induced bone pain. ⋯ Chronic intraperitoneal treatment with sinomenine markedly suppressed the activation of microglia and effectively inhibited the expression of JAK2/STAT3 and CAMKII/CREB signaling pathways. We are the first to reveal that up-regulation of microglial JAK2/STAT3 pathway are involved in the development and maintenance of cancer-induced bone pain. Moreover, our investigation provides the first evidence that sinomenine alleviates cancer-induced bone pain by inhibiting microglial JAK2/STAT3 and neuronal CAMKII/CREB cascades.
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Meta Analysis Comparative Study
Comparison of the efficacy and safety of non-steroidal anti-inflammatory drugs for patients with primary dysmenorrhea: A network meta-analysis.
Objective Non-steroidal anti-inflammatory drugs are used as first-line treatment of primary dysmenorrhea, but there has been no optimal clinical choice among non-steroidal anti-inflammatory drugs yet. The present study was to assess the relative benefits of different common non-steroidal anti-inflammatory drugs for primary dysmenorrhea patients with a network meta-analysis. Methods Randomized controlled trials were screened by our criteria and included in the network meta-analysis. ⋯ According to the results of network analysis and surface under cumulative ranking curve, flurbiprofen was considered to be the best one among all the treatments in efficacy, and aspirin was worse than most of others. On the other hand, tiaprofenic acid and mefenamic acid were indicated as the safest drugs. Conclusion Considering the efficacy and safety, we recommended flurbiprofen and tiaprofenic acid as the optimal treatments for primary dysmenorrhea.
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Meta Analysis
[EXPRESS] Quantitative Evaluation to Efficacy and Safety of Therapies for Psoriasis: A Network Meta-Analysis.
Therapies treating psoriasis can be categorized into five classes according to their mechanism: anti-metabolites (AM), anti-interleukin-12/23 agents (anti-IL12/23), anti-interleukin-17 agents (anti-IL17), anti-T-cell agent (ANT), and anti-tumor necrosis factor-α agent (anti-TNF-α). This network meta-analysis (NMA) aimed to give a quantitative and systemic evaluation of safety and efficacy for the five kinds of therapies mentioned above. Odds ratios and mean differences were calculated to evaluate binary and continuous outcomes, respectively. ⋯ Additionally, node splitting showed that no inconsistency appeared between the direct and indirect comparisons. Anti-IL12/23 was the most recommended therapy according to this NMA. Anti-IL17 had similar efficacy to anti-IL12/23 but should be applied with caution since it has poor performance in safety outcomes.
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Primary sensory neurons in the dorsal root ganglia and trigeminal ganglia are responsible for sensing mechanical and thermal stimuli, as well as detecting tissue damage. These neurons express ion channels that respond to thermal, mechanical, or chemical cues, conduct action potentials, and mediate transmitter release. These neurons also express a large number of G-protein coupled receptors, which are major transducers for extracellular signaling molecules, and their activation usually modulates the primary transduction pathways. ⋯ On the other hand, receptors that couple to Gi/o proteins, such as opioid or GABAB receptors, are generally inhibitory. Their activation counteracts the effect of Gs-stimulation by inhibiting adenylate cyclase, as well as exerts effects on ion channels, usually resulting in decreased excitability. This review will summarize knowledge on Gi-coupled receptors in sensory neurons, focusing on their roles in ion channel regulation and discuss their potential as targets for analgesic and antipruritic medications.