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https://www.readbyqxmd.com/read/28214378/calcium-signaling-through-l-type-calcium-channels-role-in-pathophysiology-of-spinal-nociceptive-transmission
#1
REVIEW
Olivier Roca-Lapirot, Houda Radwani, Franck Aby, Frédéric Nagy, Marc Landry Pascal Fossat
L-type voltage-gated calcium channels (VGCCs) are ubiquitous channels in the central nervous system. L-type calcium channels (LTCs) are mostly post-synaptic channels regulating neuronal firing and gene expression. They play a role in important physio-pathological processes such as learning and memory, Parkinson's disease, autism and, as recognized more recently, in the pathophysiology of pain processes. Classically, the fundamental role of these channels in cardiovascular functions has limited the use of classical molecules to treat LTC-dependent disorders...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28211895/electroacupuncture-attenuates-cfa-induced-inflammatory-pain-by-suppressing-nav1-8-through-s100b-trpv1-opioid-and-adenosine-pathways-in-mice
#2
Hsien-Yin Liao, Ching-Liang Hsieh, Chun-Ping Huang, Yi-Wen Lin
Pain is associated with several conditions, such as inflammation, that result from altered peripheral nerve properties. Electroacupuncture (EA) is a common Chinese clinical medical technology used for pain management. Using an inflammatory pain mouse model, we investigated the effects of EA on the regulation of neurons, microglia, and related molecules. Complete Freund's adjuvant (CFA) injections produced a significant mechanical and thermal hyperalgesia that was reversed by EA or a transient receptor potential V1 (TRPV1) gene deletion...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199982/n-acetyl-cysteine-attenuates-remifentanil-induced-postoperative-hyperalgesia-via-inhibiting-matrix-metalloproteinase-9-in-dorsal-root-ganglia
#3
Yue Liu, Yuan Ni, Wei Zhang, Yu-E Sun, Zhengliang Ma, Xiaoping Gu
Treatment of remifentanil-induced postoperative hyperalgesia (RIH) remains a clinical challenge because the mechanisms are not fully understood. Matrix metalloproteinase-9 (MMP-9) is a key component in neuroinflammation because of its facilitation of pro-inflammatory cytokine maturation. Therefore, inhibition of MMP-9 may represent a novel therapeutic approach to the treatment of RIH. Sprague-Dawley rats were randomly divided into three groups: Control, Incision and Remifentanil. A right plantar surgical incision was performed in Group Incision, and intraoperative remifentanil (0...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28197201/-three-methods-and-three-points-regulates-p38-mitogen-activated-protein-kinase-in-the-dorsal-horn-of-the-spinal-cord-in-a-rat-model-of-sciatic-nerve-injury
#4
Xin Guo, Tian-Yuan Yu, Wong Steven, Wen-Duan Jia, Chi Ma, Yan-Hong Tao, Chao Yang, Tao-Tao Lv, Shuai Wu, Meng-Qian Lu, Jia-Li Liu
Tuina is a traditional Chinese treatment for sensory disturbances caused by peripheral nerve injury and related diseases. Our previous studies showed that tuina regulates relevant regions and indices of the spinal dorsal horn using the Dian, Bo, and Rou method in Yinmen (BL37), Yanglingquan (GB34), and Weizhong (BL40). Treatment prevents muscle atrophy, protects spinal cord neurons, and promotes sciatic nerve repair. The mechanisms of action of tuina for treating peripheral nerve injury remain poorly understood...
December 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28182698/prevention-of-remifentanil-induced-postoperative-hyperalgesia-by-dexmedetomidine-via-regulating-the-trafficking-and-function-of-spinal-nmda-receptors-as-well-as-pkc-and-camkii-level-in-vivo-and-in-vitro
#5
Yuan Yuan, Zhe Sun, Yi Chen, Yuxin Zheng, Ke-Liang Xie, Ying He, Zhifen Wang, Guo-Lin Wang, Yong-Hao Yu
Remifentanil-induced secondary hyperalgesia has been demonstrated in both animal experiments and clinical trials. Enhancement of N-methyl-D-aspartate (NMDA) receptor trafficking as well as protein kinase C (PKC) and calmodulin-dependent protein kinase II (CaMKII) have been reported to be involved in the induction and maintenance of central sensitization. In the current study, it was demonstrated that dexmedetomidine could prevent remifentanil-induced hyperalgesia (RIH) via regulating spinal NMDAR-PKC-Ca2+/ CaMKII pathway in vivo and in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28181190/distribution-of-alox15-in-the-rat-brain-and-its-role-in-prefrontal-cortical-resolvin-d1-formation-and-spatial-working-memory
#6
Suku-Maran Shalini, Christabel Fung-Yih Ho, Yee-Kong Ng, Jie-Xin Tong, Eng-Shi Ong, Deron R Herr, Gavin S Dawe, Wei-Yi Ong
Docosahexaenoic acid (DHA) is enriched in membrane phospholipids of the central nervous system (CNS) and has a role in aging and neuropsychiatric disorders. DHA is metabolized by the enzyme Alox15 to 17S-hydroxy-DHA, which is then converted to 7S-hydroperoxy,17S-hydroxy-DHA by a 5-lipoxygenase, and thence via epoxy intermediates to the anti-inflammatory molecule, resolvin D1 (RvD1 or 7S,8R,17S-trihydroxy-docosa-Z,9E,11E,13Z,15E,19Z-hexaenoic acid). In this study, we investigated the distribution and function of Alox15 in the CNS...
February 8, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28177520/broad-spectrum-efficacy-with-ly2969822-an-oral-prodrug-of-metabotropic-glutamate-2-3-mglu2-3-receptor-agonist-ly2934747-in-rodent-pain-models
#7
Michael P Johnson, Mark A Muhlhauser, Eric S Nisenbaum, Rosa M A Simmons, Beth M Forster, Kelly L Knopp, Lijuan Yang, Denise Morrow, Dominic L Li, Jeffrey D Kennedy, Steven Swanson, James A Monn
BACKGROUND AND PURPOSE: A body of evidence suggests activation of metabotropic glutamate 2/3 (mGlu2/3 ) receptors would be an effective analgesic in chronic pain conditions. Thus, the analgesic properties of a novel mGlu2/3 receptor agonist prodrug were investigated. EXPERIMENTAL APPROACH: After oral absorption, the prodrug LY2969822 rapidly converts to the brain penetrant, potent, and subtype-selective mGlu2/3 receptor agonist LY2934747. Behavioral assessments of allodynia, hyperalgesia, or nocifensive behaviors in preclinical pain models were determined after administration of LY2969822 of 0...
February 8, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28166306/identification-of-shared-risk-loci-and-pathways-for-bipolar-disorder-and-schizophrenia
#8
Andreas J Forstner, Julian Hecker, Andrea Hofmann, Anna Maaser, Céline S Reinbold, Thomas W Mühleisen, Markus Leber, Jana Strohmaier, Franziska Degenhardt, Jens Treutlein, Manuel Mattheisen, Johannes Schumacher, Fabian Streit, Sandra Meier, Stefan Herms, Per Hoffmann, André Lacour, Stephanie H Witt, Andreas Reif, Bertram Müller-Myhsok, Susanne Lucae, Wolfgang Maier, Markus Schwarz, Helmut Vedder, Jutta Kammerer-Ciernioch, Andrea Pfennig, Michael Bauer, Martin Hautzinger, Susanne Moebus, Lorena M Schenk, Sascha B Fischer, Sugirthan Sivalingam, Piotr M Czerski, Joanna Hauser, Jolanta Lissowska, Neonila Szeszenia-Dabrowska, Paul Brennan, James D McKay, Adam Wright, Philip B Mitchell, Janice M Fullerton, Peter R Schofield, Grant W Montgomery, Sarah E Medland, Scott D Gordon, Nicholas G Martin, Valery Krasnov, Alexander Chuchalin, Gulja Babadjanova, Galina Pantelejeva, Lilia I Abramova, Alexander S Tiganov, Alexey Polonikov, Elza Khusnutdinova, Martin Alda, Cristiana Cruceanu, Guy A Rouleau, Gustavo Turecki, Catherine Laprise, Fabio Rivas, Fermin Mayoral, Manolis Kogevinas, Maria Grigoroiu-Serbanescu, Tim Becker, Thomas G Schulze, Marcella Rietschel, Sven Cichon, Heide Fier, Markus M Nöthen
Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. BD shows substantial clinical and genetic overlap with other psychiatric disorders, in particular schizophrenia (SCZ). The genes underlying this etiological overlap remain largely unknown. A recent SCZ genome wide association study (GWAS) by the Psychiatric Genomics Consortium identified 128 independent genome-wide significant single nucleotide polymorphisms (SNPs). The present study investigated whether these SCZ-associated SNPs also contribute to BD development through the performance of association testing in a large BD GWAS dataset (9747 patients, 14278 controls)...
2017: PloS One
https://www.readbyqxmd.com/read/28162807/a-brainstem-spinal-cord-inhibitory-circuit-for-mechanical-pain-modulation-by-gaba-and-enkephalins
#9
Amaury François, Sarah A Low, Elizabeth I Sypek, Amelia J Christensen, Chaudy Sotoudeh, Kevin T Beier, Charu Ramakrishnan, Kimberly D Ritola, Reza Sharif-Naeini, Karl Deisseroth, Scott L Delp, Robert C Malenka, Liqun Luo, Adam W Hantman, Grégory Scherrer
Pain thresholds are, in part, set as a function of emotional and internal states by descending modulation of nociceptive transmission in the spinal cord. Neurons of the rostral ventromedial medulla (RVM) are thought to critically contribute to this process; however, the neural circuits and synaptic mechanisms by which distinct populations of RVM neurons facilitate or diminish pain remain elusive. Here we used in vivo opto/chemogenetic manipulations and trans-synaptic tracing of genetically identified dorsal horn and RVM neurons to uncover an RVM-spinal cord-primary afferent circuit controlling pain thresholds...
February 22, 2017: Neuron
https://www.readbyqxmd.com/read/28158164/rapid-and-delayed-effects-of-pulsed-radiofrequency-on-neuropathic-pain-electrophysiological-molecular-and-behavioral-evidence-supporting-long-term-depression
#10
Ren-Yu Huang, Chia-Chi Liao, Shih-Ying Tsai, Chen-Tung Yen, Chii-Wann Lin, Tsung-Chi Chen, Wei-Tso Lin, Chi-Heng Chang, Yeong-Ray Wen
BACKGROUND: Pulsed radiofrequency (PRF) has been widely employed for ameliorating clinical neuropathic pain. How PRF alters electrophysiological transmission and modulates biomolecular functions in neural tissues has yet to be clarified. We previously demonstrated that an early application of low-voltage bipolar PRF adjacent to the dorsal root ganglion (DRG) reduced acute neuropathic pain in animals. By contrast, the present study investigated how PRF alters postsynaptic sensitization to produce early and delayed effects on neuropathic pain...
February 2017: Pain Physician
https://www.readbyqxmd.com/read/28134928/blocking-microglial-pannexin-1-channels-alleviates-morphine-withdrawal-in-rodents
#11
Nicole E Burma, Robert P Bonin, Heather Leduc-Pessah, Corey Baimel, Zoe F Cairncross, Michael Mousseau, Jhenkruthi Vijaya Shankara, Patrick L Stemkowski, Dinara Baimoukhametova, Jaideep S Bains, Michael C Antle, Gerald W Zamponi, Catherine M Cahill, Stephanie L Borgland, Yves De Koninck, Tuan Trang
Opiates are essential for treating pain, but termination of opiate therapy can cause a debilitating withdrawal syndrome in chronic users. To alleviate or avoid the aversive symptoms of withdrawal, many of these individuals continue to use opiates. Withdrawal is therefore a key determinant of opiate use in dependent individuals, yet its underlying mechanisms are poorly understood and effective therapies are lacking. Here, we identify the pannexin-1 (Panx1) channel as a therapeutic target in opiate withdrawal...
January 30, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28130358/inhibition-mediated-by-glycinergic-and-gabaergic-receptors-on-excitatory-neurons-in-mouse-superficial-dorsal-horn-is-location-specific-but-modified-by-inflammation
#12
Tomonori Takazawa, Papiya Choudhury, Chi-Kun Tong, Charles M Conway, Grégory Scherrer, Pamela D Flood, Jun Mukai, Amy B MacDermott
: The superficial dorsal horn is the synaptic termination site for many peripheral sensory fibers of the somatosensory system. A wide range of sensory modalities are represented by these fibers including pain, itch and temperature. Because local inhibition in the dorsal horn, specifically that mediated by the inhibitory amino acids GABA and glycine, is importantly involved in signal processing there, we investigated regional inhibitory control of excitatory interneurons under control conditions and peripheral inflammation-induced mechanical allodynia...
January 27, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28125674/characterisation-of-immune-and-neuroinflammatory-changes-associated-with-chemotherapy-induced-peripheral-neuropathy
#13
Preet G S Makker, Samuel S Duffy, Justin G Lees, Chamini J Perera, Ryan S Tonkin, Oleg Butovsky, Susanna B Park, David Goldstein, Gila Moalem-Taylor
Chemotherapy-induced peripheral neuropathy (CIPN) and associated neuropathic pain is a debilitating adverse effect of cancer treatment. Current understanding of the mechanisms underpinning CIPN is limited and there are no effective treatment strategies. In this study, we treated male C57BL/6J mice with 4 cycles of either Paclitaxel (PTX) or Oxaliplatin (OXA) over a week and tested pain hypersensitivity and changes in peripheral immune responses and neuroinflammation on days 7 and 13 post 1st injection. We found that both PTX and OXA caused significant mechanical allodynia...
2017: PloS One
https://www.readbyqxmd.com/read/28123022/tnf-%C3%AE-differentially-regulates-synaptic-plasticity-in-the-hippocampus-and-spinal-cord-by-microglia-dependent-mechanisms-after-peripheral-nerve-injury
#14
Yong Liu, Li-Jun Zhou, Jun Wang, Dai Li, Wen-Jie Ren, Jiyun Peng, Xiao Wei, Ting Xu, Wen-Jun Xin, Rui-Ping Pang, Yong-Yong Li, Zhi-Hai Qin, Madhuvika Murugan, Mark P Mattson, Long-Jun Wu, Xian-Guo Liu
: Clinical studies show that chronic pain is accompanied by memory deficits and reduction in hippocampal volume. Experimental studies show that spared nerve injury (SNI) of the sciatic nerve induces long-term potentiation (LTP) at C-fiber synapses in spinal dorsal horn, but impairs LTP in the hippocampus. The opposite changes may contribute to neuropathic pain and memory deficits, respectively. However, the cellular and molecular mechanisms underlying the functional synaptic changes are unclear...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28120884/phosphorylated-histone-3-at-serine-10-identifies-activated-spinal-neurons-and-contributes-to-the-development-of-tissue-injury-associated-pain
#15
Jose Vicente Torres-Pérez, Péter Sántha, Angelika Varga, Peter Szucs, Joao Sousa-Valente, Botond Gaal, Miklós Sivadó, Anna P Andreou, Sara Beattie, Bence Nagy, Klara Matesz, J Simon C Arthur, Gábor Jancsó, Istvan Nagy
Transcriptional changes in superficial spinal dorsal horn neurons (SSDHN) are essential in the development and maintenance of prolonged pain. Epigenetic mechanisms including post-translational modifications in histones are pivotal in regulating transcription. Here, we report that phosphorylation of serine 10 (S10) in histone 3 (H3) specifically occurs in a group of rat SSDHN following the activation of nociceptive primary sensory neurons by burn injury, capsaicin application or sustained electrical activation of nociceptive primary sensory nerve fibres...
January 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28111162/hud-mediated-distinct-bdnf-regulatory-pathways-promote-regeneration-after-nerve-injury
#16
Maria Domenica Sanna, Carla Ghelardini, Nicoletta Galeotti
Up-regulation of brain-derived neurotrophic factor (BDNF)synthesis is an important mechanism of peripheralnerveregenerationafterinjury.However, the cellular and molecular mechanisms underlying this process are not fully understood. This study examines the role of BDNF in the spared nerve injury (SNI) mice model. Protein expression and cellular localization were investigated in the dorsal root ganglia (DRG) and spinal cord by western blotting and immunofluorescence experiments respectively. BDNF protein was markedly increased 3 and 7 days post-injury in the spinal cord and DRG...
January 19, 2017: Brain Research
https://www.readbyqxmd.com/read/28097463/neurokinin-1-receptor-immunopositive-neurons-in-the-medullary-dorsal-horn-provide-collateral-axons-to-both-the-thalamus-and-parabrachial-nucleus-in-rats
#17
Xu Li, Shun-Nan Ge, Yang Li, Han-Tao Wang
It has been suggested that the trigemino-thalamic and trigemino-parabrachial projection neurons in the medullary dorsal horn (MDH) are highly implicated in the sensory-discriminative and emotional/affective aspects of orofacial pain, respectively. In previous studies, some neurons were reported to send projections to both the thalamus and parabrachial nucleus by way of collaterals in the MDH. However, little is known about the chemoarchitecture of this group of neurons. Thus, in the present study, we determined whether the neurokinin-1 (NK-1) receptor, which is crucial for primary orofacial pain signaling, was expressed in MDH neurons co-innervating the thalamus and parabrachial nucleus...
January 17, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28094445/presynaptic-inhibition-of-transient-receptor-potential-vanilloid-type-1-trpv1-receptors-by-norepinephrine-in-nociceptive-neurons
#18
Saikat Chakraborty, Vincent Elvezio, Martin Kaczocha, Mario Rebecchi, Michelino Puopolo
The transient receptor potential vanilloid type 1 (TRPV1) receptor is a well-known contributor to nociceptor excitability. To address whether norepinephrine can down-regulate TRPV1 channel activity in nociceptors and reduce their synaptic transmission, the effects of norepinephrine and clonidine were tested on the capsaicin-activated current recorded from acutely dissociated small diameter (<27 μm) dorsal root ganglia (DRG) neurons and on miniature excitatory postsynaptic currents (mEPSCs) recorded from large lamina I neurons in horizontal spinal cord slices...
January 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28088231/efficacy-of-gabapentin-for-prevention-of-postherpetic-neuralgia-study-protocol-for-a-randomized-controlled-clinical-trial
#19
Manuel Rullán, Oana Bulilete, Alfonso Leiva, Aina Soler, Antonia Roca, María José González-Bals, Patricia Lorente, Joan Llobera
BACKGROUND: Postherpetic neuralgia (PHN) is a chronic neuropathic pain that results from alterations of the peripheral nervous system in areas affected by the herpes zoster virus. The symptoms include pain, paresthesia, dysesthesia, hyperalgesia, and allodynia. Despite the availability of pharmacological treatments to control these symptoms, no treatments are available to control the underlying pathophysiology responsible for this disabling condition. METHODS/DESIGN: Patients with herpes zoster who are at least 50 years old and have a pain score of 4 or higher on a visual analogue scale (VAS) will be recruited...
January 14, 2017: Trials
https://www.readbyqxmd.com/read/28072604/epigenetic-upregulation-of-cxcl12-expression-mediates-anti-tubulin-chemotherapeutics-induced-neuropathic-pain
#20
Ting Xu, Xiao-Long Zhang, Han-Dong Ou-Yang, Zhen-Yu Li, Cui-Cui Liu, Zhen-Zhen Huang, Jing Xu, Jia-You Wei, Bi-Lin Nie, Chao Ma, Shao-Ling Wu, Wen-Jun Xin
Clinically, Microtubule-targeted agents-induced neuropathic pain hampers chemotherapeutics for cancer patients. Here, we found that application of paclitaxel or vincristine increased the protein and mRNA expression of CXCL12, and frequency and amplitude of miniature excitatory post synaptic currents (mEPSCs) in spinal dorsal horn neurons. Spinal local application of CXCL12 induced the long-term potentiation (LTP) of nociceptive synaptic transmission and increased the amplitude of mEPSCs. Inhibition of CXCL12 by using the transgenic mice (CXCL12) or neutralizing antibody or siRNA ameliorated the mEPSCs enhancement and mechanical allodynia...
January 7, 2017: Pain
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