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Neuropathic plasticity

Georgios Baskozos, John M Dawes, Jean S Austin, Ana Antunes-Martins, Lucy McDermott, Alex J Clark, Teodora Trendafilova, Jon G Lees, Stephen B McMahon, Jeffrey S Mogil, Christine Orengo, David L Bennett
Dorsal root ganglion (DRG) neurons provide connectivity between peripheral tissues and spinal cord. Transcriptional plasticity within DRG sensory neurons after peripheral nerve injury contributes to nerve repair but also leads to maladaptive plasticity, including the development of neuropathic pain. This study presents tissue and neuron specific expression profiling of both known and novel Long Non-Coding RNAs (LncRNAs) in rodent DRG following nerve injury. We have identified a large number of novel LncRNAs expressed within rodent DRG, a minority of which were syntenically conserved between mouse, rat and human and which including both- intergenic and antisense LncRNAs...
October 16, 2018: Pain
Yong Fang Zhu, Jacek M Kwiecien, Wojciech Dabrowski, Robert Ungard, Kan Lun Zhu, Jan D Huizinga, James L Henry, Gurmit Singh
Evidence suggests that there are both nociceptive and neuropathic components of cancer-induced pain (CIP). We have observed that changes in intrinsic membrane properties and excitability of normally non-nociceptive Aβ sensory neurons are consistent in rat models of peripheral neuropathic pain (NEP) and CIP. This has prompted a comparative investigation of the intracellular electrophysiological characteristics of sensory neurons and of the ultrastructural morphology of the dorsal horn in rat models of NEP and CIP...
October 16, 2018: Molecular Pain
X Moisset, J-P Lefaucheur
The use of medications in chronic neuropathic pain may be limited with regard to efficacy and tolerance. Therefore, non-pharmacological approaches, using electrical stimulation of the cortex has been proposed as an alternative. First, in the early nineties, surgically-implanted epidural motor cortex stimulation (EMCS) was proven to be effective to relieve refractory neuropathic pain. Later, non-invasive stimulation techniques were found to produce similar analgesic effects, at least by means of repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex (M1)...
October 12, 2018: Revue Neurologique
Ken-Ichiro Hayashida, James C Eisenach
Gabapentinoids are effective in a wide range of animal pain models and in patients with neuropathic pain and has become one of first-line treatments for neuropathic pain. Because spinal plasticity and sensitization have been intensely studied in neuropathic pain, most laboratory studies have focused on actions of gabapentinoids in the spinal cord, where they reduce primary afferent traffic and excitation of spinal nociceptive neurons, via interaction with α2δ subunits of voltage-gated Ca2+ channels. However, a recent clinical study questioned the relevance of this in vitro and in vivo rodent studies by demonstrating a complete lack of clinical efficacy of intrathecal gabapentin in patients with chronic pain...
2018: Advances in Experimental Medicine and Biology
Tzu-Hao Harry Chao, Jyh-Horng Chen, Chen-Tung Yen
Neuropathic pain is a major worldwide health problem. Although central sensitization has been reported in well-established neuropathic conditions, information on the acute brain activation patterns in response to peripheral nerve injury is lacking. This study first mapped the brain activity in rats immediately following spared nerve injury (SNI) of the sciatic nerve. Using blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD-fMRI), we observed sustained activation in the bilateral insular cortices (ICs), primary somatosensory cortex (S1), and cingulate cortex...
October 1, 2018: Molecular Brain
Serena Boccella, Claudia Cristiano, Rosaria Romano, Monica Iannotta, Carmela Belardo, Antonio Farina, Francesca Guida, Fabiana Piscitelli, Enza Palazzo, Mariacristina Mazzitelli, Roberta Imperatore, Lea Tunisi, Vito de Novellis, Luigia Cristino, Vincenzo Di Marzo, Antonio Calignano, Sabatino Maione, Livio Luongo
Chronic pain is associated with cognitive deficits. Palmitoylethanolamide (PEA) has been shown to ameliorate pain and pain-related cognitive impairments by restoring glutamatergic synapses functioning in the spared nerve injury (SNI) of the sciatic nerve in mice. SNI reduced mechanical and thermal threshold, spatial memory and LTP at the lateral entorhinal cortex (LEC)-dentate gyrus (DG) pathway. It decreased also postsynaptic density, volume and dendrite arborization of DG and increased the expression of metabotropic glutamate receptor 1 and 7 (mGluR1 and mGluR7), of the GluR1, GluR1s845 and GluR1s831 subunits of AMPA receptor and the levels of glutamate in the DG...
September 25, 2018: Neurobiology of Disease
Kohei Matsubayashi, Narihito Nagoshi, Yuji Komaki, Kota Kojima, Munehisa Shinozaki, Osahiko Tsuji, Akio Iwanami, Ryosuke Ishihara, Norio Takata, Morio Matsumoto, Masaru Mimura, Hideyuki Okano, Masaya Nakamura
Neural connectivity has recently been shown to be altered after spinal cord injury (SCI) not only in the spinal cord but also in the brain. However, to date, no studies have analyzed the functional alterations after SCI in various areas of the cerebral cortex over time. To examine the plasticity of the neural connectivity in the brain after SCI, we performed resting-state functional magnetic resonance imaging (rs-fMRI) in awake adult mice pre- and post-SCI. After a complete thoracic SCI, the functional connectivity between the primary motor (MOp) and primary sensory (SSp) areas was significantly decreased during the chronic phase...
September 26, 2018: Scientific Reports
Max Ortiz-Catalan
Phantom limb pain (PLP) is a debilitating condition common after amputation that can considerably hinder patients' quality of life. Several treatments have reported promising results in alleviating PLP. However, clinical evaluations are usually performed in small cohorts and rigorous clinical trials are scarce. In addition, the underlying mechanisms by which novel interventions alleviate PLP are often unclear, potentially because the condition itself is poorly understood. This article presents a theoretical framework of PLP that can be used as groundwork for hypotheses of novel treatments...
2018: Frontiers in Neurology
Yu Zhao, Zhanyun Yang
Neuropathic pain (NP) is a common clinical chronic pain with very complex mechanisms. This study explored the function of activated Wnt signaling pathway in NP. A rat model of chronic constriction injury (CCI) was established. Different doses of IWP-2, a Wnt signal inhibitor, were intrathecally injected to observe the behavior indicators at different time-points, including the pain induced by mechanical stimulation and thermal stimulation. The mRNA and protein levels of Wnt-3a, Frizzled 4 and β-catenin in lumbar (L) 4-6 dorsal root ganglion (DRG) of rats in each group, as well as synaptic plasticity-related molecules in DRG region of rats were detected by RT-PCR and western blotting, respectively...
October 2018: Experimental and Therapeutic Medicine
Xingrui Gong, Yongmei Chen, Jing Chang, Yue Huang, Meihau Cai, Mazhong Zhang
BACKGROUND: Infant nerve injury causes delayed adolescent neuropathic pain, but whether it also leads to psychiatric illness is unknown. Environmental enrichment (EE) increases social communication and activity. Thus, our goal was to test anxiety- and depression-like behaviors after infant peripheral nerve injury and evaluate the effect of environmental enrichment on these models of affective disorders. METHODS: Open field, elevated plus maze, sucrose preference, and pain behaviors (paw withdrawal threshold, spontaneous guarding score, and cold response to acetone) were measured in rats that received infant spared nerve injury (SNI)...
September 12, 2018: Journal of Neuroinflammation
Yu-Chia Chuang, Cheng-Han Lee, Wei-Hsin Sun, Chih-Cheng Chen
Advillin is a sensory neuron-specific actin-binding protein expressed at high levels in all types of somatosensory neurons in early development. However, the precise role of advillin in adulthood is largely unknown. Here we reveal advillin expression restricted to isolectin B4-positive (IB4+ ) neurons in the adult dorsal root ganglia (DRG). Advillin knockout (KO) specifically impaired axonal regeneration in adult IB4+ DRG neurons. During axon regeneration, advillin was expressed at the very tips of filopodia and modulated growth cone formation by interacting with and regulating focal-adhesion-related proteins...
September 4, 2018: Proceedings of the National Academy of Sciences of the United States of America
Mohammed Zacky Ariffin, Khairunisa Mohamad Ibrahim, Andy Thiam-Huat Lee, Rui Zhi Lee, Shou Yu Poon, Hwai Kit Thong, Eugene Hern Choon Liu, Chian-Ming Low, Sanjay Khanna
The present study explored the role of the medial septal region (MS) in experimental neuropathic pain. For the first time, we found that the MS sustains nociceptive behaviors in rodent models of neuropathic pain, especially in the chronic constriction injury (CCI) model and the paclitaxel model of chemotherapy-induced neuropathic pain. For example, inactivation of the MS with intraseptal muscimol (2 μg/μl, 0.5 μl), a GABA mimetic, reversed peripheral hypersensitivity (PH) in the CCI model and induced place preference in a conditioned place preference task, a surrogate measure of spontaneous nociception...
August 8, 2018: Scientific Reports
Laís Silva Fernandes, Neife Aparecida G Dos Santos, Guilherme Luz Emerick, Antonio Cardozo Dos Santos
Organophosphorus (OPs) compounds have been widely used in agriculture, industry, and household, and the neurotoxicity induced by them is still a cause of concern. The main toxic mechanism of OPs is the inhibition of acetylcholinesterase (AChE); however, the delayed neuropathy induced by OPs (OPIDN) is mediated by other mechanisms such as the irreversible inhibition of 70% of NTE activity (neuropathy target esterase) that leads to axonal degeneration. Liraglutide is a long-lasting GLP-1 analog clinically used as antidiabetic...
August 7, 2018: Neurotoxicity Research
Serena Boccella, Francesca Guida, Francesco De Logu, Danilo De Gregorio, Mariacristina Mazzitelli, Carmela Belardo, Monica Iannotta, Nicola Serra, Romina Nassini, Vito de Novellis, Pierangelo Geppetti, Sabatino Maione, Livio Luongo
The mechanisms underlying neuropathic pain are poorly understood. Here we show the unexplored role of the hydroxyl carboxylic acid receptor type 2 (HCAR2) in 2 models of neuropathic pain. We used an oral treatment with dimethyl fumarate and the HCAR2 endogenous ligand β-hydroxybutyrate (BHB) in wild-type (WT) and HCAR2-null mice. We found an up-regulation of the HCAR2 in the sciatic nerve and the dorsal root ganglia in neuropathic mice. Accordingly, acute and chronic treatment with dimethylfumarate (DMF) and BHB reduced the tactile allodynia...
August 7, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Martin Kotev, Rosalia Pascual, Carmen Almansa, Victor Guallar, Robert Soliva
Cryo-electron microscopy (cryo-EM) is emerging as a real alternative for structural elucidation. In spite of this, very few cryo-EM structures have been described so far as successful platforms for in silico drug design. Gabapentin and pregabalin are some of the most successful drugs in the treatment of epilepsy and neuropathic pain. Although both are in clinical use and are known to exert their effects by binding to the regulatory α2δ subunit of voltage gated calcium channels, their binding modes have never been characterized...
August 27, 2018: Journal of Chemical Information and Modeling
Ming-Chun Hsieh, Yu-Cheng Ho, Cheng-Yuan Lai, Dylan Chou, Gin-Den Chen, Tzer-Bin Lin, Hsien-Yu Peng
Presynaptic active zone proteins play a crucial role in regulating synaptic plasticity. Although the ubiquitin-proteasome system underlying the degradation of the presynaptic active zone protein is well established, the contribution of this machinery to regulating spinal plasticity during neuropathic pain development remains unclear. Here, using male Sprague Dawley rats, we demonstrated along with behavioral allodynia, neuropathic injury induced a marked elevation in the expression levels of an active zone protein Munc13-1 in the homogenate and synaptic plasma membrane of the ipsilateral dorsal horn...
July 24, 2018: Cell Death & Disease
Sun Woo Um, Min Jee Kim, Joong Woo Leem, Sun Joon Bai, Bae Hwan Lee
The anterior cingulate cortex (ACC) is a well-known brain area that is associated with pain perception. Previous studies reported that the ACC has a specific role in the emotional processing of pain. Chronic pain is characterized by long-term potentiation that is induced in pain pathways and contributes to hyperalgesia caused by peripheral nerve injury. The mammalian target of rapamycin (mTOR) signaling, which is involved in synaptic protein synthesis, could be a key factor controlling long-term potentiation in neuropathic pain conditions...
July 22, 2018: Molecular Neurobiology
Stephanie Shiers, Grishma Pradhan, Juliet Mwirigi, Galo Mejia, Ayesha Ahmad, Sven Kroener, Theodore Price
Chronic pain patients suffer from pain-related cognitive deficits, even when taking commonly prescribed analgesics. These deficits are likely related to pain-related maladaptive plasticity in the frontal cortex. We sought to model cognitive deficits in mice with neuropathic pain to examine maladaptive morphological plasticity in the mPFC and to assess the effects of several therapeutics. We used an attentional set-shifting task in mice with spared nerve injury (SNI) who received either a single intrathecal injection of an analgesic dose of clonidine, 7 d of 100 mg/kg gabapentin, or 7 d of 200 mg/kg metformin...
August 15, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Takufumi Yanagisawa, Ryohei Fukuma, Ben Seymour, Koichi Hosomi, Haruhiko Kishima, Takeshi Shimizu, Hiroshi Yokoi, Masayuki Hirata, Toshiki Yoshimine, Yukiyasu Kamitani, Youichi Saitoh
A brachial plexus root avulsion (BPRA) causes intractable pain in the insensible affected hands. Such pain is partly due to phantom limb pain, which is neuropathic pain occurring after the amputation of a limb and partial or complete deafferentation. Previous studies suggested that the pain was attributable to maladaptive plasticity of the sensorimotor cortex. However, there is little evidence to demonstrate the causal links between the pain and the cortical representation, and how much cortical factors affect the pain...
August 15, 2018: Neurologia Medico-chirurgica
Nayereh Ghoreishi-Haack, Jessica M Priebe, Jacqueline D Aguado, Elizabeth M Colechio, Jeffrey S Burgdorf, M Scott Bowers, Cassia N Cearley, M Amin Khan, Joseph R Moskal
NYX-2925 [(2S,3R)-3-hydroxy-2-((R)-5-isobutyryl-1-oxo-2,5-diazaspiro[3.4]octan-2-yl)butanamide] is a novel N -methyl-d-aspartate (NMDA) receptor modulator that is currently being investigated in phase 2 clinical studies for the treatment of painful diabetic peripheral neuropathy and fibromyalgia. Previous studies demonstrated that NYX-2925 is a member of a novel class of NMDA receptor-specific modulators that affect synaptic plasticity processes associated with learning and memory. Studies here examined NYX-2925 administration in rat peripheral chronic constriction nerve injury (CCI) and streptozotocin-induced diabetic mechanical hypersensitivity...
September 2018: Journal of Pharmacology and Experimental Therapeutics
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