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https://www.readbyqxmd.com/read/28088231/efficacy-of-gabapentin-for-prevention-of-postherpetic-neuralgia-study-protocol-for-a-randomized-controlled-clinical-trial
#1
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
#2
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
https://www.readbyqxmd.com/read/28069928/functional-organization-of-cutaneous-and-muscle-afferent-synapses-onto-immature-spinal-lamina-i-projection-neurons
#3
Jie Li, Mark L Baccei
: It is well-established that sensory afferents innervating muscle are more effective at inducing hyperexcitability within spinal cord circuits compared to skin afferents, which likely contributes to the higher prevalence of chronic musculoskeletal pain compared to pain of cutaneous origin. However, the mechanisms underlying these differences in central nociceptive signaling remain incompletely understood, as nothing is known about how superficial dorsal horn (SDH) neurons process sensory input from muscle vs...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28068790/temporomandibular-disorders-old-ideas-and-new-concepts
#4
Thomas List, Rigmor Højland Jensen
Background Temporomandibular disorders (TMD) is an umbrella term for pain and dysfunction involving the masticatory muscles and the temporomandibular joints (TMJs). TMD is the most common orofacial pain condition. Its prominent features include regional pain in the face and preauricular area, limitations in jaw movement, and noise from the TMJs during jaw movements. TMD affects up to 15% of adults and 7% of adolescents. Chronic pain is the overwhelming reason that patients with TMD seek treatment. TMD can associate with impaired general health, depression, and other psychological disabilities, and may affect the quality of life of the patient...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28062308/spinal-reorganization-after-bone-fracture-in-mice
#5
Silke Hirsch, Alaa Ibrahim, Laura Krämer, Fabiola Escolano-Lozano, Tanja Schlereth, Frank Birklein
: Bone fracture with subsequent immobilization of the injured limb can cause Complex Regional Pain Syndrome (CRPS) in humans. Mechanisms of CRPS are still not completely understood but bone fracture with casting in mice leads to a similar posttraumatic inflammation as seen in humans and might therefore be an analogue to human CRPS. Here we report behavioral and spinal electrophysiological changes in mice that developed swelling of the paw, warming of the skin and pain in the injured limb after bone fracture...
January 3, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28057535/the-nitric-oxide-donor-isosorbide-dinitrate-induces-a-cephalic-cutaneous-hypersensitivity-associated-with-sensitization-of-the-medullary-dorsal-horn
#6
José María Flores Ramos, Laurent Devoize, Amélie Descheemaeker, Jean-Louis Molat, Philippe Luccarini, Radhouane Dallel
Nitric oxide donors are known to produce headache in healthy as well as migraine subjects, and to induce extracephalic cutaneous hypersensitivity in rodents. However, little is known on the effect of nitric oxide donors on cephalic cutaneous sensitivity. Combining behavioral, immunohistochemical, and in vivo electrophysiological approaches, this study investigated the effect of systemic administration of the nitric oxide donor, isosorbide dinitrate (ISDN), on cephalic and extracephalic cutaneous sensitivity and on neuronal activation within the medullary dorsal horn (MDH) in the rat...
January 3, 2017: Neuroscience
https://www.readbyqxmd.com/read/28041852/the-cellular-and-synaptic-architecture-of-the-mechanosensory-dorsal-horn
#7
Victoria E Abraira, Emily D Kuehn, Anda M Chirila, Mark W Springel, Alexis A Toliver, Amanda L Zimmerman, Lauren L Orefice, Kieran A Boyle, Ling Bai, Bryan J Song, Karleena A Bashista, Thomas G O'Neill, Justin Zhuo, Connie Tsan, Jessica Hoynoski, Michael Rutlin, Laura Kus, Vera Niederkofler, Masahiko Watanabe, Susan M Dymecki, Sacha B Nelson, Nathaniel Heintz, David I Hughes, David D Ginty
The deep dorsal horn is a poorly characterized spinal cord region implicated in processing low-threshold mechanoreceptor (LTMR) information. We report an array of mouse genetic tools for defining neuronal components and functions of the dorsal horn LTMR-recipient zone (LTMR-RZ), a role for LTMR-RZ processing in tactile perception, and the basic logic of LTMR-RZ organization. We found an unexpectedly high degree of neuronal diversity in the LTMR-RZ: seven excitatory and four inhibitory subtypes of interneurons exhibiting unique morphological, physiological, and synaptic properties...
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28039043/cathepsin-s-in-the-spinal-microglia-contributes-to-remifentanil-induced-hyperalgesia-in-rats
#8
L Ye, L Xiao, S Y Yang, J J Duan, Y Chen, Y Cui, Y Chen
Cysteine protease cathepsin S (CatS) expressed by spinal microglia has been shown to play a critical role in nerve injury and inflammation-induced chronic pain. However, whether microglial CatS contributes to remifentanil-induced acute hyperalgesia remains unstudied. In the present study, intravenous remifentanil infusion induced a significant increase in the expression of premature and mature form of CatS in the activated microglia in the spinal cord. Spinal delivery of irreversible CatS inhibitor LHVS reduced hyperalgesia, attenuated activation of spinal microglia and blocked phosphorylation of N-methyl-d-aspartate (NMDA) receptor NR1 subunit induced by remifentanil...
December 28, 2016: Neuroscience
https://www.readbyqxmd.com/read/28030475/spinal-intracellular-metabotropic-glutamate-receptor-5-mglur5-contributes-to-pain-and-c-fos-expression-in-a-rat-model-of-inflammatory-pain
#9
Kathleen Vincent, Shu Fan Wang, André Laferrière, Naresh Kumar, Terence J Coderre
Metabotropic glutamate receptor 5 (mGluR5) is an excitatory G-protein coupled receptor present in the spinal cord dorsal horn (SCDH) where it has a well-established role in pain. In addition to its traditional location on the cytoplasmic membrane, recent evidence shows that these receptors are present intracellularly on the nuclear membrane in the SCDH and are implicated in neuropathic pain. Nuclear mGluR5 is a functional receptor that binds glutamate entering the cell through the neuronal glutamate transporter (GT) EAAT3 and activates transcription factor c-fos, whereas plasma membrane mGluR5 is responsible for c-jun activation...
December 26, 2016: Pain
https://www.readbyqxmd.com/read/28028627/effect-of-electroacupuncture-on-the-cervicospinal-p2x7-receptor-fractalkine-cx3cr1-signaling-pathway-in-a-rat-neck-incision-pain-model
#10
Y H Gao, C W Li, J Y Wang, L H Tan, C L Duanmu, X H Jing, X R Chang, J L Liu
Increasing evidence supports that acupuncture intervention is an effective approach for intraoperative and postoperative pain. Neuron-microglia crosstalk, mediated by the purinergic P2X7 receptor (R)/fractalkine/CX3CR1 cascade in the spinal cord dorsal horn, plays a pivotal role in pain processing. However, its involvement in the analgesic effect of electroacupuncture (EA) remains unclear. In this study, a rat neck-incision pain model was established by making a longitudinal incision along the midline of the neck and subsequent repeated mechanical stimulation...
December 27, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/28025021/inflammatory-pain-related-traits-of-sensory-drg-neurons-innervating-the-hip-joints
#11
Takayuki Nakajima, Seiji Ohtori, Junichi Nakamura, Takane Suzuki, Yasuchika Aoki, Atsuya Watanabe, Makoto Takazawa, Kazuhisa Takahashi
BACKGROUND: Hip pain is transmitted to the dorsal horn of the spinal cord via the dorsal root ganglion (DRG), which contains two types of neurons with differential sensitivity to neurotrophic factors. If either type predominantly innervates the hip joint, it may represent a good target for hip joint pain treatment. METHODS: Inflammation was induced in the left hip joint of rats (n = 10) by using complete Freund's adjuvant. Fluoro-Gold (FG) was applied to the hip joint after 7 days, and T12-L6 DRGs were double-stained for calcitonin gene-related peptide (CGRP) and isolection-IB4 1 week later...
December 23, 2016: Journal of Orthopaedic Science: Official Journal of the Japanese Orthopaedic Association
https://www.readbyqxmd.com/read/28024908/hyp-17-a-novel-voltage-gated-sodium-channel-blocker-relieves-inflammatory-and-neuropathic-pain-in-rats
#12
Jee Youn Lee, Yoo Lim Kam, Jungae Oh, Dong Hyun Kim, Jin-Sung Choi, Hae Young Choi, Sungmin Han, Inchan Youn, Hea-Young Park Choo, Tae Young Yune
Clinical and experimental studies suggest that voltage-gated sodium channels (VGSCs) play a key role in the pathogenesis of neuropathic pain and that blocking agents against these channels can be potentially therapeutic. In the current study, we investigated whether a novel compound, (-)-2-Amino-1-(4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)-propan-1-one(HYP-17), binds to VGSCs and evaluated its inhibitory effect on Na(+) currents of the rat dorsal root ganglia (DRG) sensory neurons and its analgesic effect on inflammatory and neuropathic pain...
December 24, 2016: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28004735/blockade-of-neuronal-dopamine-d2-receptor-attenuates-morphine-tolerance-in-mice-spinal-cord
#13
Wen-Ling Dai, Feng Xiong, Bing Yan, Zheng-Yu Cao, Wen-Tao Liu, Ji-Hua Liu, Bo-Yang Yu
Tolerance induced by morphine remains a major unresolved problem and significantly limits its clinical use. Recent evidences have indicated that dopamine D2 receptor (D2DR) is likely to be involved in morphine-induced antinociceptive tolerance. However, its exact effect and molecular mechanism remain unknown. In this study we examined the effect of D2DR on morphine antinociceptive tolerance in mice spinal cord. Chronic morphine treatment significantly increased levels of D2DR in mice spinal dorsal horn. And the immunoreactivity of D2DR was newly expressed in neurons rather than astrocytes or microglia both in vivo and in vitro...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28001399/the-discovery-and-hit-to-lead-optimization-of-tricyclic-sulfonamides-as-potent-and-efficacious-potentiators-of-glycine-receptors
#14
Howard Bregman, Jeffrey R Simard, Kristin L Andrews, Shawn Ayube, Hao Chen, Hakan Gunaydin, Angel Guzman-Perez, Jiali Hu, Liyue Huang, Xin Huang, Paul H Krolikowski, Sonya G Lehto, Richard T Lewis, Klaus Michelsen, Pamela Pegman, Matthew H Plant, Paul L Shaffer, Yohannes Teffera, Shuyan Yi, Maosheng Zhang, Jacinthe Gingras, Erin F DiMauro
Current pain therapeutics suffer from undesirable psychotropic and sedative side effects, as well as abuse potential. Glycine receptors (GlyRs) are inhibitory ligand-gated ion channels expressed in nerves of the spinal dorsal horn, where their activation is believed to reduce transmission of painful stimuli. Herein, we describe the identification and hit-to-lead optimization of a novel class of tricyclic sulfonamides as allosteric GlyR potentiators. Initial optimization of high-throughput screening (HTS) hit 1 led to the identification of 3, which demonstrated ex vivo potentiation of glycine-activated current in mouse dorsal horn neurons from spinal cord slices...
December 21, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27999136/human-muse-cells-reconstruct-neuronal-circuitry-in-subacute-lacunar-stroke-model
#15
Hiroki Uchida, Kuniyasu Niizuma, Yoshihiro Kushida, Shohei Wakao, Teiji Tominaga, Cesario V Borlongan, Mari Dezawa
BACKGROUND AND PURPOSE: Multilineage-differentiating stress-enduring (muse) cells are endogenous nontumorigenic stem cells with pluripotency harvestable as pluripotent marker SSEA-3(+) cells from the bone marrow from cultured bone marrow-mesenchymal stem cells. After transplantation into neurological disease models, muse cells exert repair effects, but the exact mechanism remains inconclusive. METHODS: We conducted mechanism-based experiments by transplanting serum/xeno-free cultured-human bone marrow-muse cells into the perilesion brain at 2 weeks after lacunar infarction in immunodeficient mice...
December 20, 2016: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/27998892/tnf-%C3%AE-differentially-regulates-synaptic-plasticity-in-the-hippocampus-and-spinal-cord-by-microglia-dependent-mechanisms-after-peripheral-nerve-injury
#16
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 sciatic nerve induces long-term potentiation (LTP) at C-fiber synapses in spinal dorsal horn but impairs LTP in 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...
December 20, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27997083/acute-sacral-nerve-stimulation-reduces-visceral-mechanosensitivity-in-a-cross-organ-sensitization-model
#17
L D Langlois, E Le Long, M Meleine, M Antor, K Atmani, P Dechelotte, A M Leroi, G Gourcerol
BACKGROUND: Sacral nerve stimulation (SNS) is a surgical treatment of fecal and urinary incontinence that consists of inserting a stimulating electrode into one of the s3 or s4 sacral holes. In addition to the benefit of SNS in the treatment of incontinence, recent studies showed that SNS is effective in the treatment of irritable bowel syndrome as well as bladder pain syndrome. The aim of this study was to evaluate the effect of SNS on visceral mechanosensitivity in a cross-organ sensitization rat model...
November 7, 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/27995982/crosstalk-between-activated-microglia-and-neurons-in-the-spinal-dorsal-horn-contributes-to-stress-induced-hyperalgesia
#18
Jian Qi, Chen Chen, Qing-Xi Meng, Yan Wu, Haitao Wu, Ting-Bao Zhao
Stress has been shown to enhance pain sensitivity resulting in stress-induced hyperalgesia. However, the underlying mechanisms have yet to be elucidated. Using single-prolonged stress combined with Complete Freund's Adjuvant injection model, we explored the reciprocal regulatory relationship between neurons and microglia, which is critical for the maintenance of posttraumatic stress disorder (PTSD)-induced hyperalgesia. In our assay, significant mechanical allodynia was observed. Additionally, activated neurons in spinal dorsal horn were observed by analysis of Fos expression...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27994541/localization-of-brain-natriuretic-peptide-immunoreactivity-in-rat-spinal-cord
#19
Essam M Abdelalim, Jean-Pierre Bellier, Ikuo Tooyama
Brain natriuretic peptide (BNP) exerts its functions through NP receptors. Recently, BNP has been shown to be involved in a wide range of functions. Previous studies reported BNP expression in the sensory afferent fibers in the dorsal horn (DH) of the spinal cord. However, BNP expression and function in the neurons of the central nervous system are still controversial. Therefore, in this study, we investigated BNP expression in the rat spinal cord in detail using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry...
2016: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/27991851/semi-intact-ex-vivo-approach-to-investigate-spinal-somatosensory-circuits
#20
Junichi Hachisuka, Kyle M Baumbauer, Yu Omori, Lindsey M Snyder, H Richard Koerber, Sarah E Ross
The somatosensory input that gives rise to the perceptions of pain, itch, cold and heat are initially integrated in the superficial dorsal horn of the spinal cord. Here, we describe a new approach to investigate these neural circuits in mouse. This semi-intact somatosensory preparation enables recording from spinal output neurons, while precisely controlling somatosensory input, and simultaneously manipulating specific populations of spinal interneurons. Our findings suggest that spinal interneurons show distinct temporal and spatial tuning properties...
December 19, 2016: ELife
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