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Neuropathic plasticity

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 13, 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 medial prefrontal cortex (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 days of 100 mg/kg gabapentin, or 7 days of 200 mg/kg metformin...
July 20, 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...
July 12, 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 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 thermal and mechanical analgesic effects of NYX-2925 administration in rat peripheral chronic constriction nerve injury (CCI) and streptozotocin (STZ)-induced diabetic mechanical hypersensitivity...
July 9, 2018: Journal of Pharmacology and Experimental Therapeutics
Gloria Brunori, Jennifer Schoch, Daniela Mercatelli, Akihiko Ozawa, Lawrence Toll, Andrea Cippitelli
Tobacco smoking is particularly evident in individuals experiencing chronic pain. This complex relationship is poorly understood at both molecular and behavioral levels. Here we describe experiments aimed at understanding whether a chronic pain state induces neuroadaptations into the brain or peripheral nerves that involve nicotinic acetylcholine receptors (nAChRs) and whether these neuroadaptations directly lead to increased vulnerability to nicotine addiction or to the development of coping strategies to relieve pain symptoms...
June 21, 2018: Pain
Daiki Kato, Takashi Suto, Hideaki Obata, Shigeru Saito
BACKGROUND: Although endogenous analgesia plays an important role in controlling pain states, chronic pain patients exhibit decreased endogenous analgesia compared to healthy individuals. In rats, noxious stimulus-induced analgesia (NSIA), which is an indicator of endogenous analgesia, diminished 6 weeks after spinal nerve ligation (SNL6W). A recent study in rats with deleted noradrenergic fibers demonstrated that the noradrenergic fibers were essential to NSIA. It has also been reported that brain-derived neurotrophic factor increased spinal noradrenergic fibers...
June 20, 2018: Anesthesia and Analgesia
Clara Penas, Xavier Navarro
Accumulating evidence suggests that epigenetic alterations lie behind the induction and maintenance of neuropathic pain. Neuropathic pain is usually a chronic condition caused by a lesion, or pathological change, within the nervous system. Neuropathic pain appears frequently after nerve and spinal cord injuries or diseases, producing a debilitation of the patient and a decrease of the quality of life. At the cellular level, neuropathic pain is the result of neuronal plasticity shaped by an increase in the sensitivity and excitability of sensory neurons of the central and peripheral nervous system...
2018: Frontiers in Cellular Neuroscience
Marie L von Sperling, Hilde Høimyr, Kenneth Finnerup, Troels S Jensen, Nanna B Finnerup
Background Few studies have examined persistent pain after reduction mammaplasty, and sensory changes remain a controversial subject with studies reporting both reduced, improved, and unchanged skin sensitivity following surgery. The aim of the present study was to describe the prevalence, character, and impact of sensory changes and persistent pain following breast reduction surgery and to assess possible causes and predictors of persistent sensory changes and chronic pain. Methods In May 2010, a detailed questionnaire was mailed to all 109 patients who underwent reduction mammaplasty at the Department of Plastic Surgery, Aalborg Hospital from September 2004 to February 2010...
April 1, 2011: Scandinavian Journal of Pain
L Ferhatovic, A Jelicic, M Boric, A Banozic, D Sapunar, L Puljak
Aim The aim of this study was to compare expression of total calcium/calmodulin-dependent protein kinase II (tCaMKII) and its α, β, γ and δ isoforms in dorsal root ganglion (DRG) in rat models of diabetes mellitus type I (DM1), 6 months and 1 year after diabetes induction. Methods A total of 45 male Sprague-Dawley rats weighing 160-200 g were assigned into four experimental groups: 6-months DM1 and its control group, 1-year and its control group. For the induction of DM1, after overnight fasting animals were injected intraperitonealy with 55 mg/kg of the streptozotocine (STZ)...
December 29, 2017: Scandinavian Journal of Pain
A Lind, P Emami, M Sjödin, L Katila, M Wetterhall, T Gordh, K Kultima
Aims The aim of this study was to uncover possible proteins involved in the mechanism for neuropathic spinal cord stimulation (SCS) pain relief in humans. Methods Using two different proteomic protocols we compared the protein concentration in cerebrospinal fluid (CSF) from 14 SCS responsive neuropathic pain patients using a shotgun proteomic approach. The comparison was made between samples from the same individual taken when the stimulator had been off for 48 h, and after the stimulator had been used as normal for three weeks...
December 29, 2017: Scandinavian Journal of Pain
Kangning Sang, Chaofei Bao, Yushi Xin, Shunan Hu, Xian Gao, Yongsheng Wang, Mark Bodner, Yong-Di Zhou, Xiao-Wei Dong
Clinical studies show that anxiety and chronic pain are concomitant. The neural basis for the comorbidity is unclear. The prefrontal cortex (PFC) has been recognized as a critical area for affective disorders and chronic pain modulation. In this study, we examined the role of the PFC in the pathogenesis of anxiety associated with chronic pain in a rat model of neuropathic pain with spare nerve injury (SNI). The SNI rats showed apparent anxiety-like behaviors in both open field (OF) test and elevated-plus maze (EPM) test eight weeks after surgery...
January 2018: Molecular Pain
M S Yoon, C S Koh, J Lee, J Shin, C Kong, H H Jung, J W Chang
BACKGROUND: Neuropathic pain is associated with abnormal sensitivity of the central nervous system. Although the mechanism underlying the development of sensitization remains to be fully elucidated, recent studies have reported that neuroplastic changes in the pain circuitry may be involved in hypersensitivity associated with neuropathic pain. However, it is difficult to investigate such phenomena in existing animal pain model. Therefore, in this study, we developed a novel animal model - the circuit plasticity reconstruction (CPR) model - to mimic central sensitization associated with neuroplastic changes...
June 4, 2018: European Journal of Pain: EJP
Alexander G J Skorput, Xijing Zhang, Jonathan J Waataja, Cristina D Peterson, Maureen S Riedl, Kelley F Kitto, Hai Truong, Cecilia Huffman, Stephen R Salton, Carolyn A Fairbanks, Christopher N Honda, Lucy Vulchanova
Neuroplasticity in the dorsal horn after peripheral nerve damage contributes critically to the establishment of chronic pain. The neurosecretory protein VGF (nonacronymic) is rapidly and robustly upregulated after nerve injury, and therefore, peptides generated from it are positioned to serve as signals for peripheral damage. The goal of this project was to understand the spinal modulatory effects of the C-terminal VGF-derived peptide TLQP-62 at the cellular level and gain insight into the function of the peptide in the development of neuropathic pain...
May 16, 2018: Pain
Xu Ding, Ya-Jing Liang, Li Su, Fei-Fei Liao, Dong Fang, Jun Tai, Guo-Gang Xing
Neonatal surgical injury exacerbates spinal microglial reactivity, modifies spinal synaptic function, leading to exaggerated pain hypersensitivity after adult repeated incision. Whether and how the alteration in microglial reactivity and synaptic plasticity are functionally related remain unclear. Previously, we and others have documented that spinal brain-derived neurotrophic factor (BDNF), secreted from microglia, contributes to long-term potentiation (LTP) in adult rodents with neuropathic pain. Here, we demonstrated that the mRNA and protein expression of spinal BDNF are significantly upregulated in adult rats subjected to neonatal incision and adult repeated incision (nIN-IN)...
July 15, 2018: Neuropharmacology
Ainhoa Bilbao, Claudia Falfán-Melgoza, Sarah Leixner, Robert Becker, Sathish Kumar Singaravelu, Markus Sack, Alexander Sartorius, Rainer Spanagel, Wolfgang Weber-Fahr
Neuropathic pain affects multiple brain functions, including motivational processing. However, little is known about the structural and functional brain changes involved in the transition from an acute to a chronic pain state. Here we combined behavioral phenotyping of pain thresholds with multimodal neuroimaging to longitudinally monitor changes in brain metabolism, structure and connectivity using the spared nerve injury (SNI) mouse model of chronic neuropathic pain. We investigated stimulus-evoked pain responses prior to SNI surgery, and one and twelve weeks following surgery...
April 22, 2018: Neuroscience
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