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Role of Tumor Necrosis Factor Receptor 1-Reactive Oxygen Species-Caspase 11 Pathway in Neuropathic Pain Mediated by HIV gp120 With Morphine in Rats
CONCLUSIONS: These results suggest that spinal TNFRI-mtROS-caspase 11 signal pathway plays a critical role in the HIV-associated neuropathic pain state, providing a novel approach to treating chronic pain in PLWH with opioids.PMID:36662639 | DOI:10.1213/ANE.0000000000006335
Source: Anesthesia and Analgesia - January 20, 2023 Category: Anesthesiology Authors: Kentaro Hayashi Hyun Yi Xun Zhu Shue Liu Jun Gu Keiya Takahashi Yuta Kashiwagi Marta Pardo Hirotsugu Kanda Heng Li Roy C Levitt Shuanglin Hao Source Type: research

LncRNA MRAK159688 facilitates morphine tolerance by promoting REST-mediated inhibition of mu opioid receptor in rats
Neuropharmacology. 2022 Jan 1;206:108938. doi: 10.1016/j.neuropharm.2021.108938. Online ahead of print.ABSTRACTMorphine tolerance (MT) caused by the long-term use of morphine is a major medical problem. The molecular mechanism of morphine tolerance remains elusive. Here, we established a morphine tolerance model in rats and verified whether the long noncoding RNA (lncRNA) MRAK159688 is involved in morphine tolerance and its specific molecular mechanism. We show the significant upregulation of MRAK159688 expression in the spinal cord of morphine-tolerant rats. Overexpression of MRAK159688 by a lentivirus reduces the analges...
Source: Neuropharmacology - January 4, 2022 Category: Drugs & Pharmacology Authors: Meiling Deng Zengli Zhang Manyu Xing Xia Liang Zhengyiqi Li Jing Wu Shasha Jiang Yingqi Weng Qulian Guo Wangyuan Zou Source Type: research

Chronic morphine-mediated upregulation of high mobility group box 1 in the spinal cord contributes to analgesic tolerance and hyperalgesia in rats
We examined whether spinal high mobility group box 1 (HMGB1) is involved in morphine tolerance and its underlying mechanisms by using a model of repeated intrathecal (i.t.) injections of morphine. The results showed that chronic i.t. morphine exposure led to increased expression of HMGB1, Toll-like receptor 4 (TLR4), and receptor for advanced glycation end products (RAGE) and their mRNAs in the dorsal horn. Morphine challenge also promoted HMGB1 expression and release in cultured spinal neurons, but these effects were inhibited by TAK-242, naloxone (antagonists of TLR4), and TLR4 siRNA. Intrathecal coadministration of morp...
Source: Neurotherapeutics - December 25, 2019 Category: Neurology Source Type: research

Connecting Metainflammation and Neuroinflammation Through the PTN-MK-RPTP β/ζ Axis: Relevance in Therapeutic Development
Conclusion The expression of the components of the PTN-MK-RPTPβ/ζ axis in immune cells and in inflammatory diseases suggests important roles for this axis in inflammation. Pleiotrophin has been recently identified as a limiting factor of metainflammation, a chronic pathological state that contributes to neuroinflammation and neurodegeneration. Pleiotrophin also seems to potentiate acute neuroinflammation independently of the inflammatory stimulus while MK seems to play different -even opposite- roles in acute neuroinflammation depending on the stimulus. Which are the functions of MK and PTN in chronic neuroi...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research

Contribution of dorsal root ganglion octamer transcription factor 1 to neuropathic pain after peripheral nerve injury
In this study, we investigated whether octamer transcription factor 1 (OCT1), a transcription factor, contributed to neuropathic pain caused by chronic constriction injury (CCI) of the sciatic nerve. Chronic constriction injury produced a time-dependent increase in the level of OCT1 protein in the ipsilateral L4/5 DRG, but not in the spinal cord. Blocking this increase through microinjection of OCT1 siRNA into the ipsilateral L4/5 DRG attenuated the initiation and maintenance of CCI-induced mechanical allodynia, heat hyperalgesia, and cold allodynia and improved morphine analgesia after CCI, without affecting basal respons...
Source: Pain - January 24, 2019 Category: Anesthesiology Tags: Research Paper Source Type: research

Activation of NPFFR2 leads to hyperalgesia through the spinal inflammatory mediator CGRP in mice.
Abstract Neuropeptide FF (NPFF) is recognized as an opioid modulating peptide that regulates morphine-induced analgesia. The aim of this study was to delineate the role of NPFFR2 in pain transmission. We found the expression levels of NPFF and NPFFR2 were increased in the lumbar dorsal horn of animals with CFA- and carrageenan-induced inflammation and both NPFFR2 over-expressing transgenic (NPFFR2-Tg) and NPFFR2 agonist-treated mice displayed hyperalgesia. BOLD signals from functional MRI showed that NPFFR2-Tg mice exhibited increased activation of pain-related brain regions after painful stimulation when compared...
Source: Experimental Neurology - February 4, 2017 Category: Neurology Authors: Lin YT, Liu HL, Day YJ, Chang CC, Hsu PH, Chen JC Tags: Exp Neurol Source Type: research

Opioid Receptor Expression in Neuropathic Pain Neurobiology
In this study, we determined the role of G9a in diminished MOR expression and opioid analgesic effects in animal models of neuropathic pain. We found that nerve injury in rats induced a long-lasting reduction in the expression level of MORs in the DRG but not in the spinal cord. Nerve injury consistently increased the enrichment of the G9a product histone 3 at lysine 9 dimethylation in the promoter of Oprm1 in the DRG. G9a inhibition or siRNA knockdown fully reversed MOR expression in the injured DRG and potentiated the morphine effect on pain hypersensitivity induced by nerve injury. In mice lacking Ehmt2 in DRG neurons, ...
Source: Journal of Biological Chemistry - April 14, 2016 Category: Chemistry Authors: Zhang, Y., Chen, S.-R., Laumet, G., Chen, H., Pan, H.-L. Tags: Molecular Bases of Disease Source Type: research

Epigenetics and Pain Research
i-Fect Used to Study ImpactsOur i-Fect siRNA, miRNA and shRNA Trasfection Kit was recently used to study the impact of G9a-specific siRNA (AGUAACGGGCAUCAAUGC) on Mu Opioid Receptors: Yuhao Zhang, Shao-Rui Chen, Geoffroy Laumet, Hong Chen and Hui-Lin Pan. Nerve Injury Diminishes Opioid Analgesia through Lysine Methyltransferase-Mediated Transcriptional Repression of µ-Opioid Receptors in Primary Sensory Neurons. First Published on February 25, 2016, doi: 10.1074/jbc.M115.711812... In some SNL rats, G9a-specific siRNA (4 µg) or the negative control siRNA was administered intrathecally. G9a-specific siRNA(AGUAACGGGCAUC...
Source: Neuromics - March 24, 2016 Category: Neuroscience Tags: DOR Dorsal Root Ganglia Ga9 MOR inhibitor i-Fect Morphine Mu Opioid Receptor Neuropathic Pain Source Type: news

G protein‐gated inwardly rectifying potassium (KIR3) channels play a primary role in the antinociceptive effect of oxycodone, but not morphine, at supraspinal sites
Conclusion and ImplicationsThese results demonstrate that KIR3.1 channels play a primary role in the antinociceptive effects of oxycodone, but not those of morphine, at supraspinal sites and suggest that supraspinal KIR3.1 channels are responsible for the unique analgesic profile of oxycodone.
Source: British Journal of Pharmacology - December 10, 2013 Category: Drugs & Pharmacology Authors: Atsushi Nakamura, Masahide Fujita, Hiroko Ono, Yoshie Hongo, Tomoe Kanbara, Koichi Ogawa, Yasuhide Morioka, Atsushi Nishiyori, Masahiro Shibasaki, Tomohisa Mori, Tsutomu Suzuki, Gaku Sakaguchi, Akira Kato, Minoru Hasegawa Tags: RESEARCH PAPER Source Type: research

G protein‐gated inwardly rectifying potassium (GIRK) channels play a primary role in the antinociceptive effect of oxycodone, but not morphine, at supraspinal sites
Conclusion and ImplicationsThe results demonstrated that GIRK1 channels play a primary role in the antinociceptive effects of oxycodone, but not morphine, at supraspinal sites, and suggested that supraspinal GIRK1 channels are responsible for the unique analgesic profile of oxycodone.
Source: British Journal of Pharmacology - October 7, 2013 Category: Drugs & Pharmacology Authors: Atsushi Nakamura, Masahide Fujita, Hiroko Ono, Yoshie Hongo, Tomoe Kanbara, Koichi Ogawa, Yasuhide Morioka, Atsushi Nishiyori, Masahiro Shibasaki, Tomohisa Mori, Tsutomu Suzuki, Gaku Sakaguchi, Akira Kato, Minoru Hasegawa Tags: Research Paper Source Type: research