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Hyperalgesia AMPA

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https://www.readbyqxmd.com/read/28975565/inhibition-of-%C3%AE-ark1-ameliorates-morphine-induced-tolerance-and-hyperalgesia-via-modulating-the-activity-of-spinal-nmda-receptors
#1
Xue Zhang, Shaorui Chen, Hong Chen, Huilin Pan, Yilin Zhao
Our previous study has proposed that increased presynaptic NMDARs activities play pivotal roles in the development of opioid tolerance and hyperalgesia, and blocking spinal NMDARs attenuates chronic morphine-induced synaptic plasticity and behavior. However, the cellular signaling mechanisms remain to be investigated. The aim of this research was to address the role of β-ARK1 in opioid analgesia. Opioid tolerance and hyperalgesia was induced by daily systemic morphine injections in rats for eight consecutive days...
October 3, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28859883/analgesic-effects-of-novel-lysophosphatidic-acid-receptor-5-antagonist-as2717638-in-rodents
#2
Nobuhito Murai, Hideki Hiyama, Tetsuo Kiso, Toshihiro Sekizawa, Tomonari Watabiki, Hiromasa Oka, Toshiaki Aoki
Lysophosphatidic acid (LPA) is a bioactive lipid that acts via at least six G protein-coupled receptors, LPA receptors 1-6 (LPA1-6), for various physiological functions. We examined (1) whether LPA5 is involved in pain signaling in the spinal cord; and (2) the pharmacological effects of a novel LPA5 antagonist on intrathecal prostaglandin (PG)- and (S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced allodynia, and neuropathic and inflammatory pain in rodents. Intrathecal injection of a selective LPA5 agonist, geranylgeranyl diphosphate, and a non-selective agonist, LPA, induced allodynia in wild type, but not in LPA5 knockout mice...
August 30, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28780471/neuropathic-pain-attenuating-effects-of-perampanel-in-an-experimental-model-of-chronic-constriction-injury-in-rats
#3
Ravneet Kaur Khangura, Anjana Bali, Gunjanpreet Kaur, Nirmal Singh, Amteshwar Singh Jaggi
The present study explores the pain attenuating effect of perampanel, AMPA receptor antagonist, in chronic constriction injury-induced neuropathic pain. Chronic Constriction Injury was performed by putting four loose ligatures around the sciatic nerve. Pain was assessed by determining mechanical hyperalgesia, cold allodynia and heat hyperalgesia on 7th and 14th day post surgery. Perampanel (3mg and 6mg/kg, p.o.) was administered 30min before pain assessment test on 14th day post-surgery. CCI led to significant development of pain and peak symptoms were observed on 14th day...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28669596/role-of-microglia-in-mechanical-allodynia-in-the-anterior-cingulate-cortex
#4
Keisuke Miyamoto, Kazuhiko Kume, Masahiro Ohsawa
Plastic changes that increase nociceptive transmission are observed in several brain regions under conditions of chronic pain. Synaptic plasticity in the anterior cingulate cortex (ACC) is particularly associated with neuropathic pain. Glial cells are considered candidates for the modulation of neural plastic changes in the central nervous system. In this study, we aimed to investigate the role of ACC glial cells in the development of neuropathic pain. First, we examined the expression of glial cells in the ACC of nerve-ligated mice...
June 21, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28559374/tarp-%C3%AE-2-is-required-for-inflammation-associated-ampa-receptor-plasticity-within-lamina-ii-of-the-spinal-cord-dorsal-horn
#5
Steve J Sullivan, Mark Farrant, Stuart G Cull-Candy
In the brain, transmembrane AMPAR regulatory proteins (TARPs) critically influence the distribution, gating, and pharmacology of AMPARs, but the contribution of these auxiliary subunits to AMPAR-mediated signaling in the spinal cord remains unclear. We found that the Type I TARP γ-2 (stargazin) is present in lamina II of the superficial dorsal horn, an area involved in nociception. Consistent with the notion that γ-2 is associated with surface AMPARs, CNQX, a partial agonist at AMPARs associated with Type I TARPs, evoked whole-cell currents in lamina II neurons, but such currents were severely attenuated in γ-2-lacking stargazer (stg/stg) mice...
June 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28337884/neurochemical-effects-of-photobiostimulation-in-the-trigeminal-ganglion-after-inferior-alveolar-nerve-injury
#6
D O Martins, F M Santos, L R G Britto, J B D Lemos, M Chacur
Orofacial pain is associated with peripheral and central sensitization of trigeminal nociceptive neurons. Nerve injury results in release of chemical mediators that contribute to persistent pain conditions. The activation of the transient receptor potential vanilloid 1 (TRPV1), promotes release of calcitonin gene-related peptide (CGRP) and substance P (SP) from trigeminal nerve terminals. CGRP and SP contribute to the development of peripheral hyperalgesia. The expression of SP and CGRP by primary afferent neurons is rapidly increased in response to peripheral inflammation...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28100749/promoted-interaction-of-c-ebp%C3%AE-with-demethylated-cxcr3-gene-promoter-contributes-to-neuropathic-pain-in-mice
#7
Bao-Chun Jiang, Li-Na He, Xiao-Bo Wu, Hui Shi, Wen-Wen Zhang, Zhi-Jun Zhang, De-Li Cao, Chun-Hua Li, Jun Gu, Yong-Jing Gao
DNA methylation has been implicated in the pathogenesis of chronic pain. However, the specific genes regulated by DNA methylation under neuropathic pain condition remain largely unknown. Here we investigated how chemokine receptor CXCR3 is regulated by DNA methylation and how it contributes to neuropathic pain induced by spinal nerve ligation (SNL) in mice. SNL increased Cxcr3 mRNA and protein expression in the neurons of the spinal cord. Meanwhile, the CpG (5'-cytosine-phosphate-guanine-3') island in the Cxcr3 gene promoter region was demethylated, and the expression of DNA methyltransferase 3b (DNMT3b) was decreased...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27964861/pain-opioids-and-sleep-implications-for-restless-legs-syndrome-treatment
#8
Claudia Trenkwalder, Walter Zieglgänsberger, Sam H Ahmedzai, Birgit Högl
Opioid receptor agonists are known to relieve restless legs syndrome (RLS) symptoms, including both sensory and motor events, as well as improving sleep. The mechanisms of action of opioids in RLS are still a matter of speculation. The mechanisms by which endogenous opioids contribute to the pathophysiology of this polygenetic disorder, in which there are a number of variants, including developmental factors, remains unknown. A summary of the cellular mode of action of morphine and its (partial) antagonist naloxone via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the involvement of dendritic spine activation is described...
March 2017: Sleep Medicine
https://www.readbyqxmd.com/read/27940995/promoted-interaction-of-c-ebp%C3%AE-with-demethylated-cxcr3-gene-promoter-contributes-to-neuropathic-pain-in-mice
#9
Bao-Chun Jiang, Li-Na He, Xiao-Bo Wu, Hui Shi, Wen-Wen Zhang, Zhi-Jun Zhang, De-Li Cao, Chun-Hua Li, Jun Gu, Yong-Jing Gao
DNA methylation has been implicated in the pathogenesis of chronic pain. However, the specific genes that are regulated by DNA methylation under neuropathic pain condition remain largely unknown. Here we investigated how chemokine receptor CXCR3 is regulated by DNA methylation and its contribution to neuropathic pain induced by spinal nerve ligation (SNL) in mice. SNL increased Cxcr3 mRNA and protein expression in the neurons of spinal cord. Meanwhile, the CpG island in the Cxcr3 gene promoter region was demethylated, and the expression of DNA methyltransferase 3b (DNMT3b) was decreased...
December 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27537764/pick1-regulates-the-expression-and-trafficking-of-ampa-receptors-in-remifentanil-induced-hyperalgesia
#10
Zhifen Wang, Yuan Yuan, Keliang Xie, Xiaohong Tang, Linlin Zhang, Jiying Ao, Nan Li, Yu Zhang, Suqian Guo, Guolin Wang
BACKGROUND: Remifentanil is used widely in clinical anesthesia because it induces more rapid and more common hyperalgesia than other opioid analgesics. Activation of N-methyl-D-aspartate (NMDA) receptors takes a pivotal part in remifentanil-induced hyperalgesia. Like NMDA receptors, the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are excitatory ion glutamate receptors in postsynaptic membrane, which are involved in the transmission of both acute and chronic pain...
September 2016: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/26973464/inhibition-of-spinal-ca-2-permeable-ampa-receptors-with-dicationic-compounds-alleviates-persistent-inflammatory-pain-without-adverse-effects
#11
Olga Kopach, Volodymyr Krotov, Julia Goncharenko, Nana Voitenko
Upregulation of Ca(2+)-permeable AMPA receptors (CP-AMPARs) in the dorsal horn (DH) neurons of the spinal cord has been causally linked to the maintenance of persistent inflammatory pain. Therefore, inhibition of CP-AMPARs could potentially alleviate an, otherwise, poorly treatable chronic pain. However, a loss of CP-AMPARs could produce considerable side effects because of the crucial role of CP-AMPARs in synaptic plasticity. Here we have tested whether the inhibition of spinal CP-AMPARs with dicationic compounds, the open-channel antagonists acting in an activity-dependent manner, can relieve inflammatory pain without adverse effects being developed...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/26597514/spontaneous-and-evoked-pain-associated-behaviors-in-a-rat-model-of-neuropathic-pain-respond-differently-to-drugs-with-different-mechanisms-of-action
#12
Nobuhito Murai, Toshihiro Sekizawa, Takayasu Gotoh, Tomonari Watabiki, Masayasu Takahashi, Shuichiro Kakimoto, Yuko Takahashi, Masanobu Iino, Yukinori Nagakura
Given that patients with neuropathic pain suffer a mixture of spontaneous and evoked pain symptoms, we assessed the effects of drugs with different mechanism of action on spontaneous and evoked pain-associated behaviors in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. Frequent aberrant limb movement on the operated side was measured to assess spontaneous pain-associated behavior, and mechanical allodynia and thermal hyperalgesia were evaluated to assess evoked pain-associated behaviors...
February 2016: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/26386380/ameliorative-potential-of-standardized-fruit-extract-of-pterodon-pubescens-benth-on-neuropathic-pain-in-mice-evidence-for-the-mechanisms-of-action
#13
Catharina Nucci-Martins, Daniel F Martins, Leandro F Nascimento, Dalila Venzke, Aldo S Oliveira, Marisa J S Frederico, Fátima R M B Silva, Inês M C Brighente, Moacir G Pizzolatti, Adair R S Santos
ETHNOPHARMACOLOGICAL RELEVANCE: The medicinal plant Pterodon pubescens Benth has been traditionally used for a long time to treat rheumatic diseases due to its anti-inflammatory and analgesic activities. The present study aims to evaluate the antinociceptive effect of ethanolic extract from P. pubescens fruits (EEPp) in a model of neuropathic pain in mice. MATERIALS AND METHODS: The phytochemical analysis of EEPp was performed through GC-MS, HPLC and colorimetric analysis...
December 4, 2015: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/26335908/glun2b-n-methyl-d-aspartate-receptor-and-excitatory-amino-acid-transporter-3-are-upregulated-in-primary-sensory-neurons-after-7-days-of-morphine-administration-in-rats-implication-for-opiate-induced-hyperalgesia
#14
Kerui Gong, Aditi Bhargava, Luc Jasmin
The contribution of the peripheral nervous system to opiate-induced hyperalgesia (OIH) is not well understood. In this study, we determined the changes in excitability of primary sensory neurons after sustained morphine administration for 7 days. Changes in the expression of glutamate receptors and glutamate transporters after morphine administration were ascertained in dorsal root ganglions. Patch clamp recordings from intact dorsal root ganglions (ex vivo preparation) of morphine-treated rats showed increased excitability of small diameter (≤30 μm) neurons with respect to rheobase and membrane threshold, whereas the excitability of large diameter (>30 μm) neurons remained unchanged...
January 2016: Pain
https://www.readbyqxmd.com/read/25645012/in-vivo-two-photon-imaging-of-structural-dynamics-in-the-spinal-dorsal-horn-in-an-inflammatory-pain-model
#15
Shinji Matsumura, Wataru Taniguchi, Kazuhiko Nishida, Terumasa Nakatsuka, Seiji Ito
Two-photon microscopy imaging has recently been applied to the brain to clarify functional and structural synaptic plasticity in adult neural circuits. Whereas the pain system in the spinal cord is phylogenetically primitive and easily exhibits behavioral changes such as hyperalgesia in response to inflammation, the structural dynamics of dendrites has not been analysed in the spinal cord mainly due to tissue movements associated with breathing and heart beats. Here we present experimental procedures to prepare the spinal cord sufficiently to follow morphological changes of neuronal processes in vivo by using two-photon microscopy and transgenic mice expressing fluorescent protein specific to the nervous system...
April 2015: European Journal of Neuroscience
https://www.readbyqxmd.com/read/25547463/loss-of-ica69-potentiates-long-lasting-hyperalgesia-after-subcutaneous-formalin-injection-into-the-mouse-hindpaw
#16
Qian-Jun Li, Zhen Wang, Yong-Xing Yao, Shen-Hui Jin, Mei-Zi Qian, Na-Na Li, Ya-Nan Wang, Ya-Wen Zhang, Bin-Yu Chen, Dan-Yun Jia, Ying Shen, Jun-Lu Wang
Islet-cell autoantigen 69 kDa (ICA69) plays an important role in many diseases and physiological activities by forming heteromeric complexes with protein interacts with C-kinase 1 (PICK1). PICK1 is critical for inflammatory pain hypersensitivity by regulating trafficking of AMPA receptor subunit GluA2 in spinal neurons. However, the role of ICA69 in inflammatory pain has not yet been investigated. Here we reported that expression of PICK1 in spinal cord was reduced largely in ICA69 knockout mice. The pain hypersensitivity was enhanced in the second phase 7 days after formalin administration...
March 2015: Neurochemical Research
https://www.readbyqxmd.com/read/25489099/inflammatory-sensitization-of-nociceptors-depends-on-activation-of-nmda-receptors-in-drg-satellite-cells
#17
Luiz Fernando Ferrari, Celina Monteiro Lotufo, Dionéia Araldi, Marcos A Rodrigues, Larissa P Macedo, Sérgio H Ferreira, Carlos Amilcar Parada
The present study evaluated the role of N-methyl-D-aspartate receptors (NMDARs) expressed in the dorsal root ganglia (DRG) in the inflammatory sensitization of peripheral nociceptor terminals to mechanical stimulation. Injection of NMDA into the fifth lumbar (L5)-DRG induced hyperalgesia in the rat hind paw with a profile similar to that of intraplantar injection of prostaglandin E2 (PGE2), which was significantly attenuated by injection of the NMDAR antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP-5) in the L5-DRG...
December 23, 2014: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/25253692/increased-spinal-cord-na%C3%A2-%C2%BA-k%C3%A2-%C2%BA-2cl%C3%A2-cotransporter-1-nkcc1-activity-contributes-to-impairment-of-synaptic-inhibition-in-paclitaxel-induced-neuropathic-pain
#18
Shao-Rui Chen, Lihong Zhu, Hong Chen, Lei Wen, Geoffroy Laumet, Hui-Lin Pan
Microtubule-stabilizing agents, such as paclitaxel (Taxol), are effective chemotherapy drugs for treating many cancers, and painful neuropathy is a major dose-limiting adverse effect. Cation-chloride cotransporters, such as Na(+)-K(+)-2Cl(-) cotransporter-1 (NKCC1) and K(+)-Cl(-) cotransporter-2 (KCC2), critically influence spinal synaptic inhibition by regulating intracellular chloride concentrations. Here we show that paclitaxel treatment in rats significantly reduced GABA-induced membrane hyperpolarization and caused a depolarizing shift in GABA reversal potential of dorsal horn neurons...
November 7, 2014: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/25126703/glycogen-synthase-kinase-3%C3%AE-inhibition-prevents-remifentanil-induced-postoperative-hyperalgesia-via-regulating-the-expression-and-function-of-ampa-receptors
#19
Yi-ze Li, Xiao-hong Tang, Chun-yan Wang, Nan Hu, Ke-liang Xie, Hai-yun Wang, Yong-hao Yu, Guo-lin Wang
BACKGROUND: Many studies have confirmed that brief remifentanil exposure can enhance pain sensitivity. We previously reported that activation of glycogen synthase kinase-3β (GSK-3β) contributes to remifentanil-induced hyperalgesia via regulating N-methyl-D-aspartate receptor plasticity in the spinal dorsal horn. In this study, we demonstrated that GSK-3β inhibition prevented remifentanil-induced postoperative hyperalgesia via regulating α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) expression and function in the spinal dorsal horn...
October 2014: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/24584020/-contribution-of-the-sensitization-of-supraspinal-nociceptive-transmission-in-chronic-pain
#20
REVIEW
Masahiro Ohsawa, Shohei Yamamoto, Hideki Ono
Central sensitization in the spinal cord is well known to be involved in chronic pain. Recent investigations indicated that the protein expressions involving the synaptic plasticity are changed in several brain areas under a chronic pain condition. These changes in supraspinal neural function might cause the emotional and memory dysfunction. It is also possible that these changes are involved in the chronic pain. Indeed, since the improvement of spinal and peripheral sensitization showed limited relief in the neuropathic pain, the sensitization of supraspinal nociceptive transmission might be involved in the expression of chronic pain...
2014: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
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