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stress and neuropathic pain

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https://www.readbyqxmd.com/read/27917874/discovery-synthesis-biological-evaluation-and-structure-based-optimization-of-novel-piperidine-derivatives-as-acetylcholine-binding-protein-ligands
#1
Jian Shen, Xi-Cheng Yang, Ming-Cheng Yu, Li Xiao, Xun-Jie Zhang, Hui-Jiao Sun, Hao Chen, Guan-Xin Pan, Yu-Rong Yan, Si-Chen Wang, Wei Li, Lu Zhou, Qiong Xie, Lin-Qian Yu, Yong-Hui Wang, Li-Ming Shao
The homomeric α7 nicotinic receptor (α7 nAChR) is widely expressed in the human brain that could be activated to suppress neuroinflammation, oxidative stress and neuropathic pain. Consequently, a number of α7 nAChR agonists have entered clinical trials as anti-Alzheimer's or anti-psychotic therapies. However, high-resolution crystal structure of the full-length α7 receptor is thus far unavailable. Since acetylcholine-binding protein (AChBP) from Lymnaea stagnalis is most closely related to the α-subunit of nAChRs, it has been used as a template for the N-terminal domain of α-subunit of nAChR to study the molecular recognition process of nAChR-ligand interactions, and to identify ligands with potential nAChR-like activities...
December 5, 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27868328/long-term-outcome-of-the-adjustable-transobturator-male-system-atoms-results-of-a-european-multicentre-study
#2
Alexander Friedl, Sandra Mühlstädt, Roman Zachoval, Alessandro Giammò, Danijel Kivaranovic, Maximilian Rom, Paolo Fornara, Clemens Brössner
OBJECTIVE: To evaluate the long-term effectiveness and safety of the adjustable transobturator male system (ATOMS(®) , Agency for Medical Innovations A.M.I., Feldkirch, Austria) in a European-wide multicentre setting. PATIENTS AND METHODS: In all, 287 men with stress urinary incontinence (SUI) were treated with the ATOMS device between June 2009 and March 2016. Continence parameters (daily pad test/pad use), urodynamics (maximum urinary flow rate, voiding volume, residual urine), and pain/quality of life (QoL) ratings (visual analogue scale/Leeds Assessment of Neuropathic Symptoms and Signs, International Consultation on Incontinence Questionnaire-Short Form [ICIQ-SF]/Patient Global Impression of Improvement [PGI-I]) were compared preoperatively and after intermediate (12 months) as well as after individual maximum follow-up...
November 21, 2016: BJU International
https://www.readbyqxmd.com/read/27856286/nox4-is-an-early-initiator-of-neuropathic-pain
#3
Christian Geis, Eva Geuss, Claudia Sommer, Harald H H W Schmidt, Christoph Kleinschnitz
Treatment of neuropathic pain remains challenging as the etiology is heterogeneous and pathomechanisms are incompletely understood. One possible mechanism is oxidative stress due to unphysiological reactive oxygen species (ROS) formation. The only know dedicated enzymatic source of ROS are NADPH oxidases of which the type 4 isoform (NOX4) has been suggested to be involved in the subacute and chronic phase of neuropathic pain. Here, we aim to translate this finding into a treatment strategy by examining the efficacy of the NOX1/4-specific inhibitor GKT136901 using the chronic constriction injury (CCI) mouse model of neuropathic pain...
November 14, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27811555/targeting-the-endocannabinoid-system-in-psychiatric-illness
#4
Martin A Katzman, Melissa Furtado, Leena Anand
Prevalence of psychiatric disorders continues to rise globally, yet remission rates and patient outcome remain less than ideal. As a result, novel treatment approaches for these disorders are necessary to decrease societal economic burden, as well as increase individual functioning. The recent discovery of the endocannabinoid system has provided an outlet for further research into its role in psychiatric disorders, because efficacy of targeted treatments have been demonstrated in medical illnesses, including cancers, neuropathic pain, and multiple sclerosis...
December 2016: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/27799181/mitovite-a-mitochondria-targeted-antioxidant-limits-paclitaxel-induced-oxidative-stress-and-mitochondrial-damage-in-vitro-and-paclitaxel-induced-mechanical-hypersensitivity-in-a-rat-pain-model
#5
B McCormick, D A Lowes, L Colvin, C Torsney, H F Galley
BACKGROUND: Neuropathic pain is a common side-effect of chemotherapy. Although precise mechanisms are unclear, oxidative stress and mitochondrial damage are involved. We investigated whether the mitochondria targeted antioxidant, MitoVitE, provided better protection against paclitaxel-induced mitochondrial damage in rat dorsal root ganglion (DRG) cells, than a non-targeted form of vitamin E, Trolox. We also determined whether MitoVitE, compared with duloxetine, could limit paclitaxel-induced mechanical hypersensitivity in rats...
November 2016: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/27778243/activation-of-the-nuclear-factor-e2-related-factor%C3%A2-2-anitioxidant-response-element-alleviates-the-nitroglycerin-induced-hyperalgesia-in-rats
#6
Wei Di, Xiaolei Shi, Hua Lv, Jun Liu, Hong Zhang, Zhiwei Li, Yannan Fang
BACKGROUND: Antioxidants have been proven to weaken hyperalgesia in neuropathic pain. Endogenous antioxidant defense system may have a role in the prevention of hyperalgesia in migraine. In this study, we aimed to evaluate the role of nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) pathway in regulating the activation of the trigeminovascular system (TGVS) and hypersensitivity in nitroglycerin (NTG)-induced hyperalgesia rats. METHODS: The expression levels of Nrf2, HO, HO1, and NQO1 in the trigeminal nucleus caudalis (TNC) were detected by western blot...
December 2016: Journal of Headache and Pain
https://www.readbyqxmd.com/read/27773810/incidence-and-risk-factors-for-pelvic-pain-after-mesh-implant-surgery-for-the-treatment-of-pelvic-floor-disorders
#7
Elizabeth J Geller, Emma Babb, Andrea G Nackley, Denniz Zolnoun
STUDY OBJECTIVE: Our aim was to assess incidence and risk factors for pelvic pain after pelvic mesh implantation. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: Single university hospital. PATIENTS: Women who have undergone surgery with pelvic mesh implant for treatment of pelvic floor disorders including prolapse and incontinence. INTERVENTIONS: Telephone interviews to assess pain, sexual function, and general health...
October 20, 2016: Journal of Minimally Invasive Gynecology
https://www.readbyqxmd.com/read/27757590/niflumic-acid-a-trpv1-channel-modulator-ameliorates-stavudine-induced-neuropathic-pain
#8
Lovish Marwaha, Yashika Bansal, Raghunath Singh, Priyanka Saroj, Rupinder Kaur Sodhi, Anurag Kuhad
TRP channels have been discovered as a specialized group of somatosensory neurons involved in the detection of noxious stimuli. Desensitization of TRPV1 located on dorsal root and trigeminal ganglia exhibits analgesic effect and makes it potential therapeutic target for treatment of neuropathic pain. With this background, the present study was aimed to investigate the protective effect of niflumic acid, a TRPV1 modulator, on stavudine (STV)-induced neuropathic pain in rats. Stavudine (50 mg/kg) was administered intravenously via tail vein in rats to induce neuropathic pain...
October 18, 2016: Inflammopharmacology
https://www.readbyqxmd.com/read/27717882/pain-modulation-from-the-brain-during-diabetic-neuropathy-uncovering-the-role-of-the-rostroventromedial-medulla
#9
Marta Silva, José Tiago Costa-Pereira, Daniel Martins, Isaura Tavares
Diabetic neuropathy has a profound impact in the quality of life of patients who frequently complain of pain. The mechanisms underlying diabetic neuropathic pain (DNP) are no longer ascribed only to damage of peripheral nerves. The effects of diabetes at the central nervous system are currently considered causes of DPN. Management of DNP may be achieved by antidepressants that act on serotonin (5-HT) uptake, namely specific serotonin reuptake inhibitors. The rostroventromedial medulla (RVM) is a key pain control center involved in descending pain modulation at the spinal cord through local release of 5-HT and plays a peculiar role in the balance of bidirectional control (i...
October 4, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27714773/histamine-h4-receptor-agonist-induced-relief-from-painful-peripheral-neuropathy-is-mediated-by-inhibition-of-spinal-neuroinflammation-and-oxidative-stress
#10
Maria Domenica Sanna, Laura Lucarini, Mariaconcetta Durante, Carla Ghelardini, Emanuela Masini, Nicoletta Galeotti
BACKGROUND AND PURPOSE: Neuropathic pain is under-treated, with a detrimental effect on quality of life, partly because of low treatment efficacy, but also because pathophysiological mechanisms are not fully elucidated. To clarify the pathobiology of neuropathic pain, we studied the contribution of neuroinflammation and oxidative stress in a model of peripheral neuropathy. We also assessed an innovative treatment for neuropathic pain by investigating the effects of histamine H4 receptor ligands in this model...
January 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27712995/combination-strategy-of-parp-inhibitor-with-antioxidant-prevent-bioenergetic-deficits-and-inflammatory-changes-in-cci-induced-neuropathy
#11
Prashanth Komirishetty, Aparna Areti, Ranadeep Gogoi, Ramakrishna Sistla, Ashutosh Kumar
Neuropathic pain, a debilitating pain condition and the underlying pathogenic mechanisms are complex and interwoven amongst each other and still there is scant information available regarding therapies which promise to treat the condition. Evidence indicate that oxidative/nitrosative stress induced poly (ADP-ribose) polymerase (PARP) overactivation initiate neuroinflammation and bioenergetic crisis culminating into neurodegenerative changes following nerve injury. Hence, we investigated the therapeutic effect of combining an antioxidant, quercetin and a PARP inhibitor, 4-amino 1, 8-naphthalimide (4-ANI) on the hallmark deficits induced by chronic constriction injury (CCI) of sciatic nerve in rats...
February 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27685701/assessment-of-somatosensory-function-in-patients-with-idiopathic-dry-eye-symptoms
#12
Anat Galor, Roy C Levitt, Katherine T McManus, Jerry P Kalangara, Benjamin E Seiden, Jasmine J Park, Derek B Covington, Constantine D Sarantopoulos, Elizabeth R Felix
Importance: Somatosensory dysfunction likely underlies dry eye (DE) symptoms in many individuals yet remains an understudied component of the disease. Its presence has important diagnostic and therapeutic implications. Objective: To assess the integrity of nociceptive system processes in persons with DE and ocular pain using quantitative sensory testing (QST) techniques applied at a site remote from the eye. Design, Setting, and Participants: A cross-sectional study conducted at Miami Veterans Affairs Hospital included 118 individuals with a wide variety of DE symptoms and signs...
November 1, 2016: JAMA Ophthalmology
https://www.readbyqxmd.com/read/27664772/regenerative-peripheral-neuropathic-pain-novel-pathological-pain-new-therapeutic-dimension
#13
You-Quan Ding, Wei-Ze Xie, Jian-Guo Qi
After peripheral nerve damage, injured or stressed primary sensory neurons (PSNs) transmitting pathological pain (pathopain) sensitize central nervous system (CNS) neural circuits and determine behavioral phenotypes of peripheral neuropathic pain (PNP). Therefore, phenotypic profiling of pathopain-transmitting PSNs is vital for probing and discovering PNP conditions. Following peripheral nerve injuries (PNIs), PNP might be potentially transmitted by distinct classes of damaged or stressed PSNs, such as axotomized PSNs without regeneration (axotomy-non-regenerative neurons), axotomized PSNs with accurate regeneration (axotomy-regenerative neurons), and spared intact PSNs adjacent to axotomized neurons (axotomy-spared neurons)...
September 24, 2016: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/27629805/progranulin-overexpression-in-sensory-neurons-attenuates-neuropathic-pain-in-mice-role-of-autophagy
#14
Christine Altmann, Stefanie Hardt, Caroline Fischer, Juliana Heidler, Hee-Young Lim, Annett Häussler, Boris Albuquerque, Béla Zimmer, Christine Möser, Christian Behrends, Frank Koentgen, Ilka Wittig, Mirko H H Schmidt, Albrecht M Clement, Thomas Deller, Irmgard Tegeder
Peripheral or central nerve injury is a frequent cause of chronic pain and the mechanisms are not fully understood. Using newly generated transgenic mice we show that progranulin overexpression in sensory neurons attenuates neuropathic pain after sciatic nerve injury and accelerates nerve healing. A yeast-2-hybrid screen revealed putative interactions of progranulin with autophagy-related proteins, ATG12 and ATG4b. This was supported by colocalization and proteomic studies showing regulations of ATG13 and ATG4b and other members of the autophagy network, lysosomal proteins and proteins involved in endocytosis...
September 11, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27561290/neuroprotective-effect-of-matrine-in-mouse-model-of-vincristine-induced-neuropathic-pain
#15
Shuai-Shuai Gong, Yu-Xiang Li, Meng-Ting Zhang, Juan Du, Peng-Sheng Ma, Wan-Xia Yao, Ru Zhou, Yang Niu, Tao Sun, Jian-Qiang Yu
Chemotherapy drugs such as vincristine (VCR) can cause neuropathic pain, and there is still lack of ideal strategy to treat it. The current study was designed to investigate effect of matrine (MT) on VCR-induced neuropathic pain in animal model. VCR (75 μg/kg, i.p. for 10 consecutive days) was administered to induce painful neuropathy model in mice. MT (15, 30 and 60 mg/kg, i.p.) and pregabalin (10 mg/kg, i.p.) were administered for 11 consecutive days. Various tests were performed to assess the degree of pain at different days (1, 6, 11, 16, and 21)...
August 25, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27504866/potential-contribution-of-antioxidant-mechanism-in-the-defensive-effect-of-lycopene-against-partial-sciatic-nerve-ligation-induced-behavioral-biochemical-and-histopathological-modification-in-wistar-rats
#16
R Goel, N Tyagi
Neuropathic pain is a severe and unbearable condition which arises due to activation of peripheral nociceptors after tissue damage, neuropathic pain is caused from anomalous physiology of central or peripheral nervous system and it may not be related to the ongoing tissue damage or inflammation. Involvement of oxidative damage has been reported in the pathophysiology of neuropathic pain. The purpose of this study was to examine the effect of lycopene to quench the free radicals produced as a result of the increased oxidative stress in neuropathic pain...
December 2016: Drug Research
https://www.readbyqxmd.com/read/27468916/response-of-the-tail-of-the-ventral-tegmental-area-to-aversive-stimuli
#17
María-José Sánchez-Catalán, Fanny Faivre, Ipek Yalcin, Marc-Antoine Muller, Dominique Massotte, Monique Majchrzak, Michel Barrot
The GABAergic tail of the ventral tegmental area (tVTA), also named rostromedial tegmental nucleus (RMTg), exerts an inhibitory control on dopamine neurons of the VTA and substantia nigra. The tVTA has been implicated in avoidance behaviors, response to drugs of abuse, reward prediction error and motor functions. Stimulation of the lateral habenula inputs to the tVTA, or of the tVTA itself, induces avoidance behaviors, which suggests a role of the tVTA in processing aversive information. Our aim was to test the impact of aversive stimuli on the molecular recruitment of the tVTA, and the behavioral consequences of tVTA lesions...
July 29, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27435304/in-vivo-and-in-vitro-protective-effects-of-omeprazole-against-neuropathic-pain
#18
Sanjay K Chanchal, Umesh B Mahajan, Sumit Siddharth, Navyya Reddy, Sameer N Goyal, Prakash H Patil, Basavaraj P Bommanahalli, Chanakya N Kundu, Chandragouda R Patil, Shreesh Ojha
Apart from reducing the acid secretion, omeprazole inhibits activation of the nuclear factor-κB, release of inflammatory cytokines, and chemotaxis of neutrophils. These mechanisms prompted us to evaluate antineuropathic effect of omeprazole in the chronic constriction injury (CCI)-induced rat model of neuropathic pain and LPS mediated ROS-induced U-87 cells. Omeprazole at 50 mg/kg/day/oral for 14 days significantly reduced the intensity of neuropathic pain estimated as paw withdrawal latency, withdrawal pressure threshold and restored the motor nerve conduction velocity in the constricted nerve, when compared with respective groups...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27414466/effect-of-ursolic-acid-in-attenuating-chronic-constriction-injury-induced-neuropathic-pain-in-rats
#19
Rafia A Bhat, Madhu C Lingaraju, Nitya N Pathak, Jaspreet Kalra, Dhirendra Kumar, Dinesh Kumar, Surendra K Tandan
Ursolic acid (UA; 3b-hydroxy-12-urs-12-en-28-oic acid), a natural pentacyclic triterpenoid carboxylic acid, has been known to possess potent anti-inflammatory, antioxidant, and antinociceptive effects in various animal models. Therefore, this study was designed to investigate the antihyperalgesic, anti-inflammatory, and antioxidant effects of UA at 5, 10, and 20 mg/kg of doses via per os (p.o.) route for 14 days in chronic constriction injury (CCI)-induced neuropathic pain in rats. Pain behavior in rats was evaluated before and after UA administration via mechanical and heat hyperalgesia...
December 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27352979/ppar%C3%AE-as-a-therapeutic-target-to-rescue-mitochondrial-function-in-neurological-disease
#20
Juan Carlos Corona, Michael R Duchen
There is increasing evidence for the involvement of mitochondrial dysfunction and oxidative stress in the pathogenesis of many of the major neurodegenerative and neuroinflammatory diseases, suggesting that mitochondrial and antioxidant pathways may represent potential novel therapeutic targets. Recent years have seen a rapidly growing interest in the use of therapeutic strategies that can limit the defects in, or even to restore, mitochondrial function while reducing free radical generation. The peroxisome proliferation-activated receptor gamma (PPARγ), a ligand-activated transcription factor, has a wide spectrum of biological functions, regulating mitochondrial function, mitochondrial turnover, energy metabolism, antioxidant defence and redox balance, immune responses and fatty acid oxidation...
June 25, 2016: Free Radical Biology & Medicine
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