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Hyperalgesia AMPA

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
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
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
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
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
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
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
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
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
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
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
Y N Liu, X Yang, Z W Suo, Y M Xu, X D Hu
BACKGROUND: Inhibition of Src-family protein tyrosine kinases (SFKs) in spinal dorsal horn has been established as an effective strategy for the alleviation of chronic pathological pain. As one of the important SFKs members, Fyn kinase is critical for synaptic plasticity and many pathophysiological processes. However, whether Fyn is involved in spinal sensitization is far from being elucidated. METHOD: We manipulated Fyn activity by expressing a constitutively active Fyn mutant [Fyn(Y528F) ] or a catalytically null mutant [Fyn(K296M) ] in the spinal dorsal horn of mice, and performed behavioural and biochemical experiments to investigate the role of Fyn in regulating the nociceptive responses and the synaptic expression of ionotropic glutamate receptors...
September 2014: European Journal of Pain: EJP
Min J Kim, Sang Y Lee, Kui Y Yang, Soon H Nam, Hyun J Kim, Young J Kim, Yong C Bae, Dong K Ahn
This study examined the differential mechanisms of mechanical allodynia and thermal hyperalgesia after injection of interleukin (IL) 1β into the orofacial area of male Sprague-Dawley rats. The subcutaneous administration of IL-1β produced both mechanical allodynia and thermal hyperalgesia. Although a pretreatment with iodoresiniferatoxin (IRTX), a transient receptor potential vanilloid 1 (TRPV1) antagonist, did not affect IL-1β-induced mechanical allodynia, it significantly abolished IL-1β-induced thermal hyperalgesia...
April 2014: Pain
Zhan-Wei Suo, Qing-Qing Fan, Xian Yang, Xiao-Dong Hu
The fast inhibitory synaptic transmission mediated by the γ-aminobutyric acid type A receptor (GABAA R) within spinal dorsal horn exerts a gating control over the synaptic conveyance of nociceptive information from the periphery to higher brain regions. Although a large body of evidence has demonstrated that the impairment of GABAergic inhibition alone is sufficient to elicit pain hypersensitivity in intact animals, the underlying mechanisms remain to be characterized. The present study shows that Ca(2+) /calmodulin-dependent protein kinase II (CaMKII) is an important signaling protein downstream of reduced GABAergic inhibition...
November 2013: Journal of Neuroscience Research
Claus Dieter Schuh, Christian Brenneis, Dong Dong Zhang, Carlo Angioni, Yannick Schreiber, Nerea Ferreiros-Bouzas, Sandra Pierre, Marina Henke, Bona Linke, Rolf Nüsing, Klaus Scholich, Gerd Geisslinger
BACKGROUND: Prostacyclin (PGI2) is known to be an important mediator of peripheral pain sensation (nociception) whereas little is known about its role in central sensitization. METHODS: The levels of the stable PGI2-metabolite 6-keto-prostaglandin F1α (6-keto-PGF1α) and of prostaglandin E2 (PGE2) were measured in the dorsal horn with the use of mass spectrometry after peripheral inflammation. Expression of the prostanoid receptors was determined by immunohistology...
February 2014: Anesthesiology
Mónica Ambriz-Tututi, Marcela Palomero-Rivero, Fernanda Ramirez-López, Diana Millán-Aldaco, And René Drucker-Colín
The role of glutamate receptors present in the medullary dorsal reticular nucleus (DRt) in the formalin test and formalin-induced secondary nociception was studied in rats. Secondary mechanical allodynia was assessed with von Frey filaments applied to the rat's hindpaw, and secondary thermal hyperalgesia was evaluated with the tail-immersion test. The selective glutamate receptor antagonists MK801 (N-methyl-D-aspartate receptor antagonist), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (AMPA/KA receptor antagonist) and A841720 (metabotropic glutamate 1 receptor antagonist) were injected into the DRt before or 6 days after formalin injection in the rat...
October 2013: European Journal of Neuroscience
Doris Gruber-Schoffnegger, Ruth Drdla-Schutting, Christoph Hönigsperger, Gabriele Wunderbaldinger, Matthias Gassner, Jürgen Sandkühler
Long-term potentiation (LTP) of synaptic strength in nociceptive pathways is a cellular model of hyperalgesia. The emerging literature suggests a role for cytokines released by spinal glial cells for both LTP and hyperalgesia. However, the underlying mechanisms are still not fully understood. In rat lumbar spinal cord slices, we now demonstrate that conditioning high-frequency stimulation of primary afferents activated spinal microglia within <30 min and spinal astrocytes within ~2 s. Activation of spinal glia was indispensible for LTP induction at C-fiber synapses with spinal lamina I neurons...
April 10, 2013: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Y Wang, J Wu, R Guo, Y Zhao, Y Wang, M Zhang, Z Chen, A Wu, Y Yue
Spinal α-amino-3-hydroxy-5-methy-4-isoxazole propionate (AMPA) receptor plays an important role in acute pain induced by surgical tissue injuries. Our previous study has shown that the enhanced phosphorylation of AMPA receptor GluR1 subunits at Serine-831 sites by protein kinase C (PKC) in the spinal cord dorsal horn is involved in post-surgical pain hypersensitivity. However, which isoforms of PKC are responsible for the phosphorylation of AMPA receptor GluR1 subunits at Serine-831 sites remains to be established...
June 14, 2013: Neuroscience
Mark S Wallace, Vicky Lam, Jared Schettler
BACKGROUND: Non-N-methyl-D-aspartate receptor subtypes modulate neurotransmitter release and mediate fast excitatory postsynaptic potentials. This study evaluated the effects of an oral prodrug to tezampanel, a selective α-amino-3-hydroxy-5-methly-4-isoxazole-proprionic acid/kainate receptor antagonist, on intradermal capsaicin-induced pain and hyperalgesia. METHODS: This was a randomized, double blind, crossover, placebo-controlled study. Eighteen subjects received 150 or 90 mg NGX426, or placebo, separated by a washout of 6 ± 2 days...
December 2012: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Olga Kopach, Viacheslav Viatchenko-Karpinski, Pavel Belan, Nana Voitenko
Persistent peripheral inflammation changes AMPA receptor (AMPAR) trafficking in dorsal horn neurons by promoting internalization of GluR2-containing, Ca(2+)-impermeable AMPARs from the synapses and by increasing insertion of GluR1-containing, Ca(2+)-permeable AMPARs in extrasynaptic plasma membrane. These changes contribute to the maintenance of persistent inflammatory pain. However, much less is known about AMPAR trafficking during development of persistent inflammatory pain and direct studies of extrasynaptic AMPARs functioning during this period are still lacking...
2012: Frontiers in Physiology
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