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https://www.readbyqxmd.com/read/28636927/noxious-but-not-innocuous-thermal-stimuli-evoke-perk-expression-in-dorsal-horn-neurons-after-spared-nerve-injury-in-adult-rats
#1
Mohamad S Samour, Sumaiya M Shaikh, David A Mahns, Peter J Shortland
Noxious stimulation of sensory afferents evokes phosphorylated extracellular signal regulated kinase (pERK) expression in spinal cord neurons. This study investigated the expression of pERK in the dorsal horn neurons in response to innocuous and noxious cold stimuli in naïve versus spared nerve injury (SNI) rats. Noxious cold or hot stimuli (0 or 45°C) elicited pERK expression in laminae I-II whereas cooling stimuli from 32°C to 25, 15 or 5°C produced no or little pERK expression in dorsal horn neurons...
June 18, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28634406/enhancing-kcc2-function-counteracts-morphine-induced-hyperalgesia
#2
Francesco Ferrini, Louis-Etienne Lorenzo, Antoine G Godin, Miorie Le Quang, Yves De Koninck
Morphine-induced hyperalgesia (MIH) is a severe adverse effect accompanying repeated morphine treatment, causing a paradoxical decrease in nociceptive threshold. Previous reports associated MIH with a decreased expression of the Cl(-) extruder KCC2 in the superficial dorsal horn (SDH) of the spinal cord, weakening spinal GABAA/glycine-mediated postsynaptic inhibition. Here, we tested whether the administration of small molecules enhancing KCC2, CLP257 and its pro-drug CLP290, may counteract MIH. MIH was typically expressed within 6-8 days of morphine treatment...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28624955/presynaptic-inhibition-of-nociceptive-neurotransmission-by-somatosensory-neuron-secreted-suppressors
#3
REVIEW
Kaicheng Li, Bing Cai, Changlin Li, Xu Zhang
Noxious stimuli cause pain by activating cutaneous nociceptors. The Aδ- and C-fibers of dorsal root ganglion (DRG) neurons convey the nociceptive signals to the laminae I-II of spinal cord. In the dorsal horn of spinal cord, the excitatory afferent synaptic transmission is regulated by the inhibitory neurotransmitter γ-aminobutyric acid and modulators such as opioid peptides released from the spinal interneurons, and by serotonin, norepinepherine and dopamine from the descending inhibitory system. In contrast to the accumulated evidence for these central inhibitors and their neural circuits in the dorsal spinal cord, the knowledge about the endogenous suppressive mechanisms in nociceptive DRG neurons remains very limited...
June 15, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28615626/neuronal-p2x7-receptor-induced-reactive-oxygen-species-production-contributes-to-nociceptive-behavior-in-mice
#4
Frances M Munoz, Ruby Gao, Yuzhen Tian, Brian A Henstenburg, James E Barrett, Huijuan Hu
ATP can activate a variety of pathways through P2 purinoreceptors, leading to neuroprotection and pathology in the CNS. Among all P2X receptors, the P2X7 receptor (P2X7R) is a well-defined therapeutic target for inflammatory and neuropathic pain. Activation of P2X7R can generate reactive oxygen species (ROS) in macrophages and microglia. However, the role of ROS in P2X7R-induced pain remains unexplored. Here, we investigated the downstream effects of neuronal P2X7R activation in the spinal cord. We found that ATP induces ROS production in spinal cord dorsal horn neurons, an effect eliminated by ROS scavenger N-tert-butyl-α-phenylnitrone (PBN) and P2X7R antagonist A438079...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615336/prevention-and-reversal-of-latent-sensitization-of-dorsal-horn-neurons-by-glial-blockers-in-a-model-of-low-back-pain-in-male-rats
#5
Juanjuan Zhang, Siegfried Mense, Rolf-Detlef Treede, Ulrich Hoheisel
In an animal model of non-specific low back pain, recordings from dorsal horn neurons were made to investigate the influence of glial cells in the central sensitization process. To induce a latent sensitization of the neurons, nerve growth factor (NGF) was injected into the multifidus muscle; the manifest sensitization to a second NGF injection 5 days later was used as a read-out. The sensitization manifested in increased resting activity and in an increased proportion of neurons responding to stimulation of deep somatic tissues...
June 14, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28612319/involvement-of-nf-%C3%AE%C2%BAb-and-the-cx3cr1-signaling-network-in-mechanical-allodynia-induced-by-tetanic-sciatic-stimulation
#6
Zhe-Chen Wang, Li-Hong Li, Chao Bian, Liu Yang, Ning Lv, Yu-Qiu Zhang
Tetanic stimulation of the sciatic nerve (TSS) triggers long-term potentiation in the dorsal horn of the spinal cord and long-lasting pain hypersensitivity. CX3CL1-CX3CR1 signaling is an important pathway in neuronal-microglial activation. Nuclear factor κB (NF-κB) is a key signal transduction molecule that regulates neuroinflammation and neuropathic pain. Here, we set out to determine whether and how NF-κB and CX3CR1 are involved in the mechanism underlying the pathological changes induced by TSS. After unilateral TSS, significant bilateral mechanical allodynia was induced, as assessed by the von Frey test...
June 13, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28608534/recent-advances-in-the-development-of-t-type-calcium-channel-blockers-for-pain-intervention
#7
REVIEW
Terrance P Snutch, Gerald W Zamponi
Cav3.2 T-type calcium channels are important regulators of pain signals in afferent pain pathway, and their activities are dysregulated during various chronic pain states. Therefore it stands to reason that inhibiting T-type calcium channels in dorsal root ganglion neurons and in the spinal dorsal horn can be targeted for pain relief. This is supported by early pharmacological studies with T-type channel blockers such as ethosuximide, and by analgesic effects of siRNA depletion of Cav3.2 channels. In the past five years, considerable effort has been applied towards identifying novel classes of T-type calcium channel blockers...
June 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28606856/antinociceptive-effect-of-botulinum-toxin-a-involves-alterations-in-ampa-receptor-expression-and-glutamate-release-in-spinal-dorsal-horn-neurons
#8
Bin Hong, LingLing Yao, Linhui Ni, Li Wang, XingYue Hu
The use of botulinum toxin A (BTX-A) for various clinical therapeutic applications is increasing. It is widely believed that peripheral therapeutic or toxic effects of BTX-A are exclusively mediated by SNAP-25 cleavage. There is growing evidence of long-distance retrograde axonal transport of BTX-A on entering the central nervous system, subsequent to a local injection of the toxin. However, the prevalence of central antinociceptive effects after BTX-A peripheral application and its underlying mechanisms are unclear...
June 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28604219/potentiation-of-nmda-receptor-mediated-synaptic-transmission-at-the-parabrachial-central-amygdala-synapses-by-cgrp-in-mice
#9
Yuya Okutsu, Yukari Takahashi, Masashi Nagase, Kei Shinohara, Ryo Ikeda, Fusao Kato
The capsular part of the central amygdala (CeC) is called the "nociceptive amygdala," as it receives nociceptive information from various pathways, including monosynaptic input from the lateral part of the parabrachial nucleus (LPB), a major target of ascending neurons in the spinal and medullary dorsal horn. LPB-CeC synaptic transmission is mediated by glutamate but the fibers from the LPB also contain calcitonin gene-related peptide (CGRP) and the CeC is rich in CGRP-binding sites. CGRP might be released in response to strong nociception and activate these CGRP receptors...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28599923/silencing-of-the-rna-binding-protein-hur-attenuates-hyperalgesia-and-motor-disability-in-experimental-autoimmune-encephalomyelitis
#10
Maria Domenica Sanna, Alessandro Quattrone, Nicoletta Galeotti
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system associated with progressive neuronal loss and axonal degeneration. Neuronal lesions and dysfunction lead often to neuropathic pain, the most prevalent and difficult to treat pain syndrome observed in MS patients. Despite its widespread occurrence, the underlying neural mechanisms for MS pain are not fully understood. For a better clarification of the pathophysiology of MS-associated pain, we investigated the role of HuR, an RNA-binding protein that positively regulates the stability of many target mRNAs, including several cytokines...
June 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28585190/spinal-ampa-receptor-glua1-ser831-phosphorylation-controls-chronic-alcohol-consumption-produced-prolongation-of-postsurgical-pain
#11
Sufang Liu, Zhiying Zhao, Yan Guo, Hui Shu, Changsheng Li, Yuanyuan Tang, Ying Xing, Feng Tao
Previous studies have shown that excessive alcohol drinking is associated with chronic pain development; however, the molecular mechanism underlying this association is poorly understood. In this study, we investigated the effect of chronic alcohol consumption on plantar incision-induced postsurgical pain. We observed that 4-week ethanol drinking significantly prolonged plantar incision-induced mechanical pain, but not thermal pain. The chronic alcohol consumption enhanced plantar incision-produced α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA1 phosphorylation at the Ser831 site in the spinal cord...
June 5, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28584816/the-lumbodorsal-fascia-as-a-potential-source-of-low-back-pain-a-narrative-review
#12
REVIEW
Jan Wilke, Robert Schleip, Werner Klingler, Carla Stecco
The lumbodorsal fascia (LF) has been proposed to represent a possible source of idiopathic low back pain. In fact, histological studies have demonstrated the presence of nociceptive free nerve endings within the LF, which, furthermore, appear to exhibit morphological changes in patients with chronic low back pain. However, it is unclear how these characteristics relate to the aetiology of the pain. In vivo elicitation of back pain via experimental stimulation of the LF suggests that dorsal horn neurons react by increasing their excitability...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28579824/tumor-necrosis-factor-%C3%AE-modulates-sodium-activated-potassium-channel-slick-in-rat-dorsal-horn-neurons-via-p38-mapk-activation-pathway
#13
Kun Wang, Feng Wang, Jun-Ping Bao, Zhi-Yang Xie, Lu Chen, Bao-Yi Zhou, Xin-Hui Xie, Xiao-Tao Wu
The dorsal horn (DH) of the spinal cord is the integrative center that processes and transmits pain sensation. Abnormal changes in ion channel expression can enhance the excitability of pain-related DH neurons. Sodium-activated potassium (KNa) channels are highly expressed particularly in the central nervous system; however, information about whether rat DH neurons express the SLICK channel protein is lacking, and the direct effects on SLICK in response to inflammation and the potential signaling pathway mediating such effects are yet to be elucidated...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28574334/modified-dorsal-root-entry-zone-lesioning-for-intractable-pain-relief-in-patients-with-root-avulsion-injury
#14
Keisuke Takai, Makoto Taniguchi
OBJECTIVE Dorsal root entry zone (DREZ) lesioning has been the most effective surgical treatment for the relief of intractable pain due to root avulsion injury, but residual pain and a decrease in pain relief in the follow-up period have been reported in 23%-70% of patients. Based on pain topography in the most recent studies on neuropathic pain, the authors modified the conventional DREZ lesioning procedure to improve clinical outcomes. The presumed rationale for this procedure is to eliminate the spontaneous discharges of neurons in the superficial spinal dorsal horn as well as wide dynamic range neurons in the deep spinal dorsal horn...
June 2, 2017: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/28573748/conditioned-pain-modulation-dampens-the-thermal-grill-illusion
#15
D E Harper, M Hollins
BACKGROUND: The thermal grill illusion (TGI) refers to the perception of burning heat and often pain that arises from simultaneous cutaneous application of innocuous warm and cool stimuli. This study utilized conditioned pain modulation (CPM) to help elucidate the TGI's underlying neural mechanisms, including the debated role of ascending nociceptive signals in generating the illusion. METHODS: To trigger CPM, subjects placed the left hand in noxious cold (6 °C) water before placing the right volar forearm onto a thermal grill...
June 2, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28565999/ryk-receptors-on-unmyelinated-nerve-fibers-mediate-excitatory-synaptic-transmission-and-ccl2-release-during-neuropathic-pain-induced-by-peripheral-nerve-injury
#16
Qing Ou Yang, Wen-Jing Yang, Jian Li, Fang-Ting Liu, Hongbin Yuan, Yue-Ping Ou Yang
Background Neuropathic pain is a major pathology of the central nervous system associated with neuroinflammation. Ryk (receptor-like tyrosine kinase) receptors act as repulsive axon-guidance molecules during development of central nervous system and neural injury. Increasing evidence suggests the potential involvement of Wnt/Ryk (wingless and Int) signaling in the pathogenesis of neuropathic pain. However, its underlying mechanism remains unknown. Results The expression and location of Ryk receptor as well as its ligand Wnt1 were detected by qPCR, Western blot, and immunohistochemistry...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28565998/gabab-receptors-mediated-tonic-inhibition-of-glutamate-release-from-a%C3%AE-fibers-in-rat-laminae-iii-iv-of-the-spinal-cord-dorsal-horn
#17
Chiara Salio, Adalberto Merighi, Rita Bardoni
Presynaptic GABAB receptors (GABABRs) are highly expressed in dorsal root ganglion neurons and spinal cord dorsal horn. GABABRs located in superficial dorsal horn play an important antinociceptive role, by acting at both pre- and postsynaptic sites. GABABRs expressed in deep dorsal horn could be involved in the processing of touch sensation and possibly in the generation of tactile allodynia in chronic pain. The objective of this study was to characterize the morphological and functional properties of GABABRs expressed on Aβ fibers projecting to lamina III/IV and to understand their role in modulating excitatory synaptic transmission...
January 2017: Molecular Pain
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
#18
Steve J Sullivan, Mark Farrant, Stuart G Cull-Candy
In the brain, transmembrane AMPA receptor (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 (SDH), 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...
May 30, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28559062/inhibitory-effect-of-angiotensin-1-7-on-angiotensin-iii-induced-nociceptive-behaviour-in-mice
#19
Wataru Nemoto, Ryota Yamagata, Yoshiki Ogata, Osamu Nakagawasai, Takeshi Tadano, Koichi Tan-No
We have previously demonstrated that the intrathecal (i.t.) administration of angiotensin (Ang) II into mice produces a nociceptive behaviour consisting of scratching, biting and licking accompanied by the phosphorylation of p38 MAPK in the spinal cord, which was mediated through AT1 receptors. Both the p38 MAPK phosphorylation and subsequent nociceptive behaviour were attenuated by the i.t. co-administration of Ang (1-7), an N-terminal fragment of Ang II, that acted via Mas receptors. On the other hand, a C-terminal fragment of Ang II, namely Ang III, was also shown to induce a nociceptive behaviour by acting upon AT1 receptors on spinal astrocytes and neurons, and was found to be more potent than Ang II...
May 23, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28542001/acetaminophen-metabolite-n-acylphenolamine-induces-analgesia-via-transient-receptor-potential-vanilloid-1-receptors-expressed-on-the-primary-afferent-terminals-of-c-fibers-in-the-spinal-dorsal-horn
#20
Nobuko Ohashi, Daisuke Uta, Mika Sasaki, Masayuki Ohashi, Yoshinori Kamiya, Tatsuro Kohno
BACKGROUND: The widely used analgesic acetaminophen is metabolized to N-acylphenolamine, which induces analgesia by acting directly on transient receptor potential vanilloid 1 or cannabinoid 1 receptors in the brain. Although these receptors are also abundant in the spinal cord, no previous studies have reported analgesic effects of acetaminophen or N-acylphenolamine mediated by the spinal cord dorsal horn. We hypothesized that clinical doses of acetaminophen induce analgesia via these spinal mechanisms...
May 25, 2017: Anesthesiology
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