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Chronic neuropathic pain

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https://www.readbyqxmd.com/read/29346515/a-brain-based-pain-facilitation-mechanism-contributes-to-painful-diabetic-polyneuropathy
#1
Andrew R Segerdahl, Andreas C Themistocleous, Dean Fido, David L Bennett, Irene Tracey
The descending pain modulatory system represents one of the oldest and most fundamentally important neurophysiological mechanisms relevant to pain. Extensive work in animals and humans has shown how a functional imbalance between the facilitatory and inhibitory components is linked to exacerbation and maintenance of persistent pain states. Forward translation of these findings into clinical populations is needed to verify the relevance of this imbalance. Diabetic polyneuropathy is one of the most common causes of chronic neuropathic pain; however, the reason why ∼25-30% of patients with diabetes develop pain is not known...
January 15, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29343707/sensory-neuronal-p2rx4-receptors-controls-bdnf-signaling-in-inflammatory-pain
#2
Sarah Lalisse, Jennifer Hua, Manon Lenoir, Nathalie Linck, François Rassendren, Lauriane Ulmann
Chronic inflammatory and neuropathic pains are major public health concerns. Potential therapeutic targets include the ATP-gated purinergic receptors (P2RX) that contribute to these pathological types of pain in several different cell types. The purinergic receptors P2RX2 and P2RX3 are expressed by a specific subset of dorsal root ganglion neurons and directly shape pain processing by primary afferents. In contrast the P2RX4 and P2RX7 are mostly expressed in myeloid cells, where activation of these receptors triggers the release of various pro-inflammatory molecules...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343689/a-novel-%C3%AE-conopeptide-eu1-6-inhibits-n-type-cav2-2-calcium-channels-and-exhibits-potent-analgesic-activity
#3
Zhuguo Liu, Peter Bartels, Mahsa Sadeghi, Tianpeng Du, Qing Dai, Cui Zhu, Shuo Yu, Shuo Wang, Mingxin Dong, Ting Sun, Jiabin Guo, Shuangqing Peng, Ling Jiang, David J Adams, Qiuyun Dai
We here describe a novel α-conopeptide, Eu1.6 from Conus eburneus, which exhibits strong anti-nociceptive activity by an unexpected mechanism of action. Unlike other α-conopeptides that largely target nicotinic acetylcholine receptors (nAChRs), Eu1.6 displayed only weak inhibitory activity at the α3β4 and α7 nAChR subtypes and TTX-resistant sodium channels, and no activity at TTX-sensitive sodium channels in rat dorsal root ganglion (DRG) neurons, or opiate receptors, VR1, KCNQ1, L- and T-type calcium channels expressed in HEK293 cells...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29342105/neuroimmune-driven-neuropathic-pain-establishment-a-focus-on-gender-differences
#4
REVIEW
Vincenzo Coraggio, Francesca Guida, Serena Boccella, Mariantonietta Scafuro, Salvatore Paino, Domenico Romano, Sabatino Maione, Livio Luongo
The role of neuroinflammatory cells in the establishment of neuropathic pain has been investigated in depth in the last few years. In particular, microglia have been shown to be key players in the induction of tactile allodynia, as they release proinflammatory molecules that, in turn, sensitize nociceptive neurons within the spinal cord. However, the role of peripheral immune cells such as macrophages, infiltrating monocytes, mast cells, and T-cells has been highlighted in the last few studies, even though the data are still conflicting and need to be clarified...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29341457/different-effects-of-dexmedetomidine-and-midazolam-on-the-expression-of-nr2b-and-gabaa-%C3%AE-1-following-peripheral-nerve-injury-in-rats
#5
Jiayu Chen, Hanjun Li, Grewo Lim, Michael F McCabe, Wei Zhao, Yunli Yang, Weiqing Ma, Na Li
Neuropathic pain is a complex, chronic pain condition and the treatment is a major clinical challenge. Recent studies have shown that two FDA approved drugs dexmedetomidine (DEX) and midazolam (MZL), may be useful in treating neuropathic pain, but the mechanism is not fully dementated. Here, we investigated the effects and mechanisms of DEX and MZL treatment in the peripheral nerve injury model. Intramuscular injection with DEX and MZL attenuated the development of mechanical allodynia and thermal hyperalgesia in rats with chronic constriction injury (CCI)...
January 17, 2018: IUBMB Life
https://www.readbyqxmd.com/read/29341331/the-relationship-between-thalamic-gaba-content-and-resting-cortical-rhythm-in-neuropathic-pain
#6
Flavia Di Pietro, Paul M Macey, Caroline D Rae, Zeynab Alshelh, Vaughan G Macefield, E Russell Vickers, Luke A Henderson
Recurrent thalamocortical connections are integral to the generation of brain rhythms and it is thought that the inhibitory action of the thalamic reticular nucleus is critical in setting these rhythms. Our work and others' has suggested that chronic pain that develops following nerve injury, that is, neuropathic pain, results from altered thalamocortical rhythm, although whether this dysrhythmia is associated with thalamic inhibitory function remains unknown. In this investigation, we used electroencephalography and magnetic resonance spectroscopy to investigate cortical power and thalamic GABAergic concentration in 20 patients with neuropathic pain and 20 pain-free controls...
January 17, 2018: Human Brain Mapping
https://www.readbyqxmd.com/read/29338150/the-role-of-cannabinoids-in-pain-control-the-good-the-bad-and-the-ugly
#7
Joseph V Pergolizzi, Jo Ann Lequang, Robert Taylor, Robert B Raffa, Daniel Colucci
Cannabinoids appear to possess many potential medical uses, which may extend to pain control. A narrative review of the literature has found a variety of studies testing botanical and synthetic cannabinoids in different pain syndromes (acute pain, cancer pain, chronic noncancer pain, fibromyalgia pain, migraine, neuropathic pain, visceral pain, and others). Results from these studies are mixed; cannabinoids appear to be most effective in controlling neuropathic pain, allodynia, medication-rebound headache, and chronic noncancer pain, but do not seem to offer any advantage over nonopioid analgesics for acute pain...
January 16, 2018: Minerva Anestesiologica
https://www.readbyqxmd.com/read/29338087/thrombospondin-4-acts-on-pre-synaptic-calcium-channel-alpha-2-delta-1-subunit-to-induce-synaptogenesis-between-sensory-and-spinal-cord-neurons-through-a-t-type-calcium-channel-dependent-pathway-that-is-blocked-by-early-low-dose-gabapentin-treatments
#8
Yanhui Peter Yu, Nian Gong, Tae Dong Kweon, Benjamin Vo, Z David Luo
BACKGROUND AND PURPOSE: Nerve injury induces concurrent upregulation of calcium channel alpha-2-delta-1 subunit (Cav α2 δ1 ) and extracellular matrix protein thrombospondin-4 (TSP4) in dorsal root ganglia and dorsal spinal cord, leading to neuropathic pain state development. Interactions of these proteins promote aberrant excitatory synaptogenesis that contributes to neuropathic pain state development through unknown mechanisms. We investigated the contributory role of Cav α2 δ1 /TSP4 to synaptogenesis, and pathway involved in vitro, and whether gabapentin could block this process and pain development in vivo...
January 16, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29337004/quantitative-sensory-testing-profiles-in-children-adolescents-and-young-adults-6-20-years-with-cerebral-palsy-hints-for-a-neuropathic-genesis-of-pain-syndromes
#9
M Blankenburg, J Junker, G Hirschfeld, E Michel, F Aksu, J Wager, B Zernikow
INTRODUCTION: Many patients with cerebral palsy (CP) suffer chronic pain as one of the most limiting factors in their quality of life. In CP patients, pain mechanisms are not well understood, and pain therapy remains a challenge. Quantitative sensory testing (QST) might provide unique information about the functional status of the somatosensory system and therefore better guide pain treatment. OBJECTIVES: To understand better the underlying pain mechanisms in pediatric CP patients, we aimed to assess clinical and pain parameters, as well as QST profiles, which were matched to the patients' cerebral imaging pathology...
December 30, 2017: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/29324503/%C3%AE-asarone-alleviated-chronic-constriction-injury-induced-neuropathic-pain-through-inhibition-of-spinal-endoplasmic-reticulum-stress-in-an-liver-x-receptor-dependent-manner
#10
Yulong Gui, Aiyuan Li, Jie Zhang, Guan Li, Xia Ruan, Qulian Guo, Wangyuan Zou
BACKGROUND: Neuropathic pain is an intractable and complex disease. Recent studies have shown a close relationship between endoplasmic reticulum (ER) stress and neuropathic pain. Here, we investigated the effect of α-asarone, an ER stress inhibitor, on chronic constriction injury (CCI)-induced neuropathic pain. METHODS: Two parts were included in this study. In part 1, rats were assigned to 7 groups: the sham group, the sham + α-asarone 20 mg/kg group, the CCI group, the CCI + vehicle group, the CCI + α-asarone 5 mg/kg group, the CCI + α-asarone 10 mg/kg group, and the CCI + α-asarone 20 mg/kg group...
January 9, 2018: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29323698/xist-accelerates-neuropathic-pain-progression-through-regulation-of-mir-150-and-zeb1-in-cci-rat-models
#11
Xue-Tao Yan, Jing-Min Lu, Yu Wang, Xiao-Li Cheng, Xiang-Hu He, Wen-Zhong Zheng, Hu Chen, Yan-Lin Wang
LncRNAs are reported to participate in neuropathic pain development. LncRNA X-inactive specific transcript (XIST) is involved in the progression of various cancers. However, the role of XIST in neuropathic pain remains unclear. In our present study, we established a chronic constriction injury (CCI) rat model and XIST was found to be greatly upregulated both in the spinal cord tissues and in the isolated microglias of CCI rats. Inhibition of XIST inhibited neuropathic pain behaviors including mechanical and thermal hyperalgesia...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29319606/disruption-of-nnos-nos1ap-protein-protein-interactions-suppresses-neuropathic-pain-in-mice
#12
Wan-Hung Lee, Li-Li Li, Aarti Chawla, Andy Hudmon, Yvonne Y Lai, Michael J Courtney, Andrea G Hohmann
Elevated N-methyl-D-aspartate receptor (NMDAR) activity is linked to central sensitization and chronic pain. However, NMDAR antagonists display limited therapeutic potential due to their adverse side effects. Novel approaches targeting the NR2B-PSD95-nNOS complex to disrupt signaling pathways downstream of NMDARs show efficacy in preclinical pain models. Here, we evaluated the involvement of interactions between neuronal nitric oxide synthase (nNOS) and the nitric oxide synthase 1 adaptor protein (NOS1AP) in pronociceptive signaling and neuropathic pain...
January 9, 2018: Pain
https://www.readbyqxmd.com/read/29316361/effects-of-serum-enzyme-thiol-and-forced-degradation-on-the-stabilities-of-%C3%AE-o-conotoxin-gexiva-1-2-and-gexiva-1-4
#13
Shurun Yu, Yong Wu, Pan Xu, Shuai Wang, Dongting Zhangsun, Sulan Luo
αO-conotoxin GeXIVA, which is a potent antagonist of α9α10 nicotinic acetylcholine receptor (nAChR), is of great interest as a potential analgesic for chronic neuropathic pain. It has three isomers, of which both GeXIVA[1,2] and GeXIVA[1,4] showed similar low nanomolar IC50 s in potent blocking rat α9α10 nAChRs. Here, we first reported stabilities of GeXIVA[1,2] and GeXIVA[1,4] in various biochemical circumstances, including human serum, enzymatic degradation and thiol, which would be the key factors to affect stabilities of the two isomers in vivo...
January 9, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29315430/swimming-training-attenuates-allodynia-and-hyperalgesia-induced-by-peripheral-nerve-injury-in-an-adult-male-rat-neuropathic-model-effects-on-irisin-and-gad65
#14
Babak Farzad, Hamid Rajabi, Reza Gharakhanlou, David J Allison, Parisa Hayat, Seyed Behnamedin Jameie
Objectives: The analgesic mechanism of long-lasting exercise on neuropathic pain is not well understood. This study explored the effects of swimming training on neuropathic pain and the expression of irisin, GAD65, and P2X3 after chronic constriction injury (CCI) of the sciatic nerve. Methods: Thirty-five male rats were randomly assigned to one of the following five groups: 1) no CCI or swimming (control); 2) swimming without CCI (SW); 3) swimming with CCI (CCISW); 4) CCI without swimming (CCI); and 5) sham CCI surgery (sham CCI)...
January 5, 2018: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/29310667/wwl70-protects-against-chronic-constriction-injury-induced-neuropathic-pain-in-mice-by-cannabinoid-receptor-independent-mechanisms
#15
Jie Wen, Melissa Jones, Mikiei Tanaka, Prabhuanand Selvaraj, Aviva J Symes, Brian Cox, Yumin Zhang
BACKGROUND: Targeting the endocannabinoid system has emerged as an effective strategy for the treatment of inflammatory and neurological diseases. Unlike the inhibition of the principal 2-arachidonyl glycerol (2-AG) hydrolytic enzyme monoacylglycerol lipase (MAGL), which leads to 2-AG overload and cannabinoid receptor desensitization, selective inhibition of the minor 2-AG hydrolytic enzyme alpha, beta-hydrolase domain 6 (ABHD6) can provide therapeutic benefits without producing cannabimimetic side effects...
January 8, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29310515/persons-with-chronic-spinal-cord-injury-have-decreased-nk-cell-and-increased-tlr-inflammatory-gene-expression
#16
Paige Herman, Adam B Stein, Katie Gibbs, Ilya Korsunsky, Peter Gregersen, Ona Bloom
Infections are the leading cause of death for individuals with traumatic spinal cord injury (SCI). Along with increased infection rates, inflammation is often also observed in persons with chronic SCI. Together, immunological changes after SCI are also poised to impede neurological recovery and to mediate common medical consequences of SCI, including atherogenesis and neuropathic pain. The molecular mechanisms contributing to increased infection susceptibility and inflammation in persons living with SCI are poorly understood...
January 8, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29307749/inflammatory-and-neuropathic-pain-from-bench-to-bedside-what-went-wrong
#17
REVIEW
Robert P Yezierski, Per Hansson
In recent years, the disappointing history of translation in the field of pain research has undergone significant scrutiny. The escalation of knowledge and understanding related to presumed pain in neuropathic and inflammatory animal models contrasted with the unsatisfactory record of "bench-to-bedside" translation has raised many questions about the validity and clinical relevance of preclinical models and methods of behavioral assessment. Although many opinions have been expressed one of the overriding concerns and greatest barriers to the widening gap between preclinical research and the development of new interventions has been the underappreciated distinction between pain and nociception...
January 4, 2018: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/29305340/evidence-from-web-based-dietary-search-patterns-to-the-role-of-b12-deficiency-in-non-specific-chronic-pain-a-large-scale-observational-study
#18
Eitan Giat, Elad Yom-Tov
BACKGROUND: Profound vitamin B12 deficiency is a known cause of disease, but the role of low or intermediate levels of B12 in the development of neuropathy and other neuropsychiatric symptoms, as well as the relationship between eating meat and B12 levels, is unclear. OBJECTIVE: The objective of our study was to investigate the role of low or intermediate levels of B12 in the development of neuropathy and other neuropsychiatric symptoms. METHODS: We used food-related Internet search patterns from a sample of 8...
January 5, 2018: Journal of Medical Internet Research
https://www.readbyqxmd.com/read/29303763/development-of-mirror-pain-following-trigeminal-nerve-injury-a-case-report-and-review-of-neuropathic-mechanisms
#19
James A Giglio, John M Gregg
Following injury to a peripheral nerve, patients may complain of pain over the distribution of the same contralateral nerve, a phenomenon referred to as contralateral pain or mirror pain (MP). Symptoms of MP usually begin after the neuropathic pain from the original nerve injury has become chronic. Chronic neuropathic pain can lead to sensitization and spread of pain. Because the diagnosis of MP can be missed, patients may undergo multiple treatment procedures that prove to be ineffective in relieving the pain...
January 2018: General Dentistry
https://www.readbyqxmd.com/read/29285962/cellular-and-molecular-mechanisms-driving-neuropathic-pain-recent-advancements-and-challenges
#20
Valencia Fernandes, Dilip Sharma, Shivani Vaidya, Shantanu P A, Yun Guan, Kiran Kalia, Vinod Tiwari
Current pharmacotherapeutics for neuropathic pain offer only symptomatic relief without treating the underlying pathophysiology. Additionally, they are associated with various dose-limiting side effects. Pain research in the past few decades has revolved around the role of oxidative-nitrosative stress, protein kinases, glial cell activation, and inflammatory signaling cascades but has failed to produce specific and effective therapies. Areas Covered: This review focuses on recent advances in cellular and molecular mechanisms of neuropathic pain that may be translated into future therapies...
December 29, 2017: Expert Opinion on Therapeutic Targets
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