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Luís A B Tonaco, Flavia L Gomes, Gustavo Velasquez-Melendez, Miriam T P Lopes, Carlos E Salas
INTRODUCTION: The aim of the study was to investigate the role of the proteolytic fraction from Vasconcellea cundinamarcensis, designated as P1G10, on the healing of chronic foot ulcers in neuropathic patients with diabetes 2. METHODS: Fifty patients were enrolled in a prospective, randomized, double-blind trial, to verify the efficacy and safety of a topical dressing formulated with 0.1% P1G10, intended for wound healing, versus a hydrogel (control) protocol. Upon completion of the intervention, the outcome evaluated the number of patients attaining full epithelization (100%), or at least 80% healing...
March 21, 2018: Advances in Therapy
James J Miller, Kazuhiro Aoki, Francie Moehring, Carly A Murphy, Crystal L O'Hara, Michael Tiemeyer, Cheryl L Stucky, Nancy M Dahms
Fabry disease, the most common lysosomal storage disease, affects multiple organs and results in a shortened life span. This disease is caused by a deficiency of the lysosomal enzyme α-galactosidase A, which leads to glycosphingolipid accumulation in many cell types. Neuropathic pain is an early and severely debilitating symptom in patients with Fabry disease, but the cellular and molecular mechanisms that cause the pain are unknown. We generated a rat model of Fabry disease, the first nonmouse model to our knowledge...
March 22, 2018: JCI Insight
Yuki Domon, Naohisa Arakawa, Tatsuya Inoue, Fumihiko Matsuda, Makoto Takahashi, Naotoshi Yamamura, Kiyonori Kai, Yutaka Kitano
Mirogabalin ([(1 R ,5 S ,6 S )-6-(aminomethyl)-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid), a novel ligand for the α2 δ subunit of voltage-gated calcium channels, is being developed to treat pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. In the present study, we investigated the in vitro binding characteristics and in vivo analgesic effects of mirogabalin, compared to those of pregabalin, a standard α2 δ ligand. Mirogabalin showed potent and selective binding affinities for the α2 δ subunits, while having no effects on 186 off-target proteins...
March 21, 2018: Journal of Pharmacology and Experimental Therapeutics
Patrick R J Fortuna, Helle Bielefeldt-Ohmann, Dmitry A Ovchinnikov, Ernst Jurgen Wolvetang, Deanne Jeanette Whitworth
Horses are susceptible to a number of neurotropic viruses, including West Nile virus (WNV), which is a pathogen of global significance in both horses and humans. However, there are no in vitro models with which to study infectious neuropathic diseases in the horse. In an effort to redress this we have generated neurons from equine induced pluripotent stem cells (equiPSCs) that express a range of cortical neuron-specific markers, in addition to the membrane-bound ligand Ephrin B3, which plays an important role in axon guidance as well as functioning as the receptor through which henipaviruses, such as Hendra virus, enter mammalian neurons...
March 21, 2018: Stem Cells and Development
Alba Finocchiaro, Sara Marinelli, Federica De Angelis, Valentina Vacca, Siro Luvisetto, Flaminia Pavone
Clinical use of neurotoxins from Clostridium botulinum is well established and is continuously expanding, including in treatment of pain conditions. Background : The serotype A (BoNT/A) has been widely investigated, and current data demonstrate that it induces analgesia and modulates nociceptive processing initiated by inflammation or nerve injury. Given that data concerning the serotype B (BoNT/B) are limited, the aim of the present study was to verify if also BoNT/B is able not only to counteract neuropathic pain, but also to interfere with inflammatory and regenerative processes associated with the nerve injury...
March 18, 2018: Toxins
Takuya Nikaido, Masahiko Sumitani, Miho Sekiguchi, Shinichi Konno
OBJECTIVES: To develop screening tools for neuropathic pain caused by spinal disorders, the Spine painDETECT questionnaire (SPDQ) and its short-form version (SF-SPDQ), by modifying the Japanese version of the painDETECT questionnaire (PDQ-J), and to validate these tools. METHODS: Using data from patients with neuropathic pain caused by spinal disorders (NeP-SD) and patients with nociceptive pain caused by joint disorders (NocP) as controls, we devised a scoring system for the SPDQ by calculating weighting coefficients for nine PDQ-J items...
2018: PloS One
Luk Van Baelen, Karin De Ridder, Jérôme Antoine, Lies Gremeaux
Background: Although gabapentin has been licensed in the European Union only for neuropathic pain and epilepsy for patients who have partial seizures, it has also been prescribed in treatment for substance use disorders. Many studies report the potential risk of abuse of gabapentin by people with substance use disorders. The objective of this paper is to determine if people who have been in treatment for substance use disorders bought gabapentin in a time span that could indicate consumption at a dose that exceeded the maximum approved dose of 3600 mg/day...
2018: Archives of Public Health, Archives Belges de Santé Publique
Kuhu Sharma, Dilip Sharma, Monika Sharma, Nishant Sharma, Pankaj Bidve, Namrata Prajapati, Kiran Kalia, Vinod Tiwari
Despite considerable advances in understanding mechanisms involved in chronic pain, effective treatment remains limited. Astaxanthin, a marine natural drug, having potent anti-oxidant and anti-inflammatory activities is known to possess neuroprotective effects. However, effects of astaxanthin against nerve injury induce chronic pain remains unknown. Overactivity of glutamatergic NMDARs results in excitotoxicity which may participate in astrocytic and microglial activation during pathology which further contribute to the development of neuropathic pain...
March 17, 2018: Neuroscience Letters
Dongdong Guo, Xinyi Hu, Haojie Zhang, Chenghua Lu, Guangwei Cui, Xingjing Luo
Neuropathic pain affects patients worldwide. The therapeutic effects of current methods are still poor. This study was performed to investigate the neuro-protective effect of orientin in rats with spinal nerve ligation (SNL). In this study, the paw mechanical withdrawal threshold (PWT) and the paw thermal withdrawal latency (PWL) behavioral assays indicated that orientin alleviated the warm and mechanical allodynia in rats with SNL. The enzyme-linked immunosorbent assay (ELISA) showed that orientin suppressed the levels of pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor alpha (TNF-α) and increased the levels of anti-inflammatory cytokine interleukin-10 (IL-10)...
March 17, 2018: International Immunopharmacology
Sumit S Sood, Christopher McClinton, Rajeev Badkul, Nathan Aguilera, Fen Wang, Allen M Chen
Purpose: The treatment of apical lung tumors with stereotactic body radiation therapy (SBRT) is challenging due to the proximity of the brachial plexus and the concern for nerve damage. Methods and materials: Between June 2009 and February 2017, a total of 75 consecutive patients underwent SBRT for T1-T3N0 non-small cell lung cancer involving the upper lobe of the lung. All patients were treated with 4-dimensional computed tomography (CT)-based image guided SBRT to a dose of 40 to 60 Gy in 3 to 5 fractions...
January 2018: Advances in Radiation Oncology
Amneh Al-Husseini, Rana Abu-Farha, Mayyada Wazaify, Marie Claire Van Hout
Objectives: Pregabalin is currently approved for the treatment of epilepsy, generalized anxiety disorder, neuropathic pain and fibromyalgia. Rising attention to the abuse liability of pregabalin causing addictive behaviors is partially based on case reports and published literature of pregabalin used in dosages that override the approved therapeutic range. This study was conducted to provide background data regarding the abuse/misuse of pregabalin from community pharmacy in Jordan. Methods: A prospective cross-sectional observational study design was used, which was conducted at different community pharmacies in Amman-Jordan...
March 2018: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
Melissa Faria, Inmaculada Fuertes, Eva Prats, Jose Luis Abad, Francesc Padrós, Cristian Gomez-Canela, Josefina Casas, Jorge Estevez, Eugenio Vilanova, Benjamin Piña, Demetrio Raldúa
Inhibition and aging of neuropathy target esterase (NTE) by exposure to neuropathic organophosphorus compounds (OPs) can result in OP-induced delayed neuropathy (OPIDN). In the present study we aimed to build a model of OPIDN in adult zebrafish. First, inhibition and aging of zebrafish NTE activity were characterized in the brain by using the prototypic neuropathic compounds cresyl saligenin phosphate (CBDP) and diisopropylphosphorofluoridate (DFP). Our results show that, as in other animal models, zebrafish NTE is inhibited and aged by both neuropathic OPs...
March 19, 2018: Scientific Reports
A M Illias, A C Gist, H Zhang, A K Kosturakis, P M Dougherty
Activation of innate immune mechanisms within the dorsal root ganglion (DRG) and spinal dorsal horn has been shown to play a key role in the development of neuropathic pain including paclitaxel-related chemotherapy-induced peripheral neuropathy (CIPN). Here we tested whether similar mechanisms are generalizable to oxaliplatin-induced CIPN. After a single intraperitoneal injection of 3mg/kg oxaliplatin, mechanical withdrawal threshold and the expression of C-C chemokine ligand 2 (CCL2) and its receptor, CCR2 in the DRG were measured by behavioral testing and immunohistochemical (IHC) staining, respectively...
March 15, 2018: Pain
Kathrin R Blume, Juliane Racz, Marcel Franz, Caroline Dietrich, Christian Puta, Reinhard Friedel, Gunther O Hofmann, Wolfgang H R Miltner, Thomas Weiss
A comprehensive functional recovery is one of the criteria for successful replantation of an amputated limb. Functionality of a replanted limb is strongly dependent on its regained sensibility. In previous studies concerning the sensibility of replanted limbs, only a few somatosensory submodalities were examined in small samples. The purpose of the present study is to provide a full pattern of somatosensory symptoms following replantation. Quantitative Sensory Testing (QST) was carried out according to a standardized protocol in a sample of 15 patients who underwent replantation of their upper limb proximal to the radiocarpal joint (macroreplantation)...
March 15, 2018: Pain
Stephen R Humble, Nicolas Varela, Asantha Jayaweera, Arun Bhaskar
PURPOSE OF REVIEW: Chronic postsurgical pain (CPSP) is an important and well recognized cause of much long-term suffering, which in some cases may be preventable and affects many people living with cancer. Unfortunately, general consensus is lacking as to how best reduce the risk of developing CPSP. RECENT FINDINGS: Cancer is now not always a short-lived, fatal disease and is now moving towards a chronic illness. Poorly managed perioperative pain is the greatest risk factor for CPSP...
March 16, 2018: Current Opinion in Supportive and Palliative Care
Yi-Chen Lee, Shui-Chin Lu, Yu-Lin Hsieh
Patients with diabetes mellitus (DM) or those experiencing the neurotoxic effects of chemotherapeutic agents may develop sensation disorders due to degeneration and injury of small-diameter sensory neurons, referred to as small fiber neuropathy. Present animal models of small fiber neuropathy affect both large- and small-diameter sensory fibers and thus create a neuropathology too complex to properly assess the effects of injured small-diameter sensory fibers. Therefore, it is necessary to develop an experimental model of pure small fiber neuropathy to adequately examine these issues...
February 13, 2018: Journal of Visualized Experiments: JoVE
Mitsufumi Nakawaki, Kensuke Fukushima, Gen Inoue, Mitsutoshi Moriya, Katsufumi Uchiyama, Naonobu Takahira, Masashi Takaso
The nature of pain associated with a labrum tear of the hip joint can vary widely among patients and does not always correlate with findings from diagnostic imaging. Identifying the components of the pain (nociceptive, neuropathic, or mixed pattern) is important to direct treatment. This report aimed to describe the use of the painDETECT questionnaire as a screening tool in order to classify the nature of the pain in three patients who presented with pain that was atypical for a labrum tear. The painDETECT questionnaire was an effective tool to identify appropriate pain management strategies in each case...
January 2018: Asia-Pacific Journal of Sports Medicine, Arthroscopy, Rehabilitation and Technology
Ying Wang, Chenyang Feng, Haoying He, Jinjin He, Jun Wang, Xiaomin Li, Shasha Wang, Wei Li, Jiuzhou Hou, Tong Liu, Dong Fang, Song-Qiang Xie
Vincristine is one of the most common anticancer drugs clinically employed in the treatment of various malignancies. A major side effect associated with vincristine is the development of neuropathic pain, which is not readily relieved by available analgesics. Although efforts have been made to identify the pathogenesis of vincristine-induced neuropathic pain, the mechanisms underlying its pathogenesis have not been fully elucidated. In the present study, a neuropathic pain model was established in Sprague-Dawley rats by intraperitoneal injection of vincristine sulfate...
April 2018: Oncology Letters
Katja Sauerstein, Jan Liebelt, Barbara Namer, Roland Schmidt, Roman Rukwied, Jürgen Sandkühler, Martin Schmelz
Secondary mechanical hyperalgesia to punctate mechanical stimuli and light touch (allodynia) are prominent symptoms in neuropathic pain states. In a combined microneurographic and psychophysical study, we investigated the role of mechano-insensitive (silent) nociceptors regarding induction. Electrical thresholds of mechano-sensitive and silent nociceptors were assessed by microneurography with two closely spaced intracutaneous electrodes (i.c.) and a transcutaneous configuration (t.c.) in the foot dorsum. For t...
March 15, 2018: Neuroscience
Crystle J Kelly, Marco Martina
Functional deactivation of the prefrontal cortex (PFC) is a critical step in the neuropathic pain phenotype. We performed optogenetic circuit dissection to study the properties of ventral hippocampal (vHipp) and thalamic (MDTh) inputs to L5 pyramidal cells in acute mPFC slices and to test whether alterations in these inputs contribute to mPFC deactivation in neuropathic pain. We found that: (1) both the vHipp and MDTh inputs elicit monosynaptic excitatory and polysynaptic inhibitory currents. (2) The strength of the excitatory MDTh input is uniform, while the vHipp input becomes progressively stronger along the dorsal-ventral axis...
March 17, 2018: Brain Structure & Function
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