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(Neuropathic Pain)

Rose Cairns, Andrea L Schaffer, Nicole Ryan, Sallie-Anne Pearson, Nicholas A Buckley
BACKGROUND AND AIMS: Pregabalin is a gamma-aminobutyric acid (GABA) analogue, used to treat neuropathic pain and epilepsy. Pregabalin was registered in Australia in 2005, and publically subsidised in 2013. We aimed to describe Australian patterns of pregabalin use and intentional poisoning, and identify people potentially at high risk of misuse. DESIGN AND SETTING: Population-based retrospective cohort study of dispensings in the 10% sample of Australian Pharmaceutical Benefits Scheme (July 2012-February 2017); intentional poisoning calls to New South Wales Poisons Information Centre (NSWPIC) (2004-2016); intentional poisonings in two Australian toxicology service databases; poisoning fatalities in NSW coronial records (2005-2016)...
August 11, 2018: Addiction
C Pitzer, C La Porta, R D Treede, A Tappe-Theodor
BACKGROUND: Chronic pain is often accompanied by comorbidities like anxiety and depression. The temporal correlations, as well as the underlying mechanisms of these reciprocal correlations, are unclear. Moreover, preclinical studies examining emotional behaviour are very controversial and a chronological analysis of anxiety-like behaviour in mouse pain models considering both genders has not been performed so far. METHODS: We used several behavioural tests to assess and validate anxiety-like behaviour in complete Freund's adjuvant (CFA) and spared nerve injury (SNI) pain models in C57BL/6 mice...
August 11, 2018: European Journal of Pain: EJP
Joy K Adewusi, Marios Hadjivassiliou, Ana Vinagre-Aragón, Karen Ruth O'Connor, Aijaz Khan, Richard Adam Grünewald, Panagiotis Zis
BACKGROUND AND PURPOSE: Pain is a frequent and debilitating non-motor symptom of Idiopathic Parkinson's Disease (IPD). The present study investigated the prevalence of pain and specifically peripheral neuropathic pain (PNP) in IPD, and ascertained any impact of PNP on quality of life (QoL). METHODS: Patients with IPD and age- and gender-matched controls were screened for overall pain using the King's Parkinson's Pain Scale (KPPS). PNP was assessed using the Michigan Neuropathy Screening Instrument (MNSI)...
September 15, 2018: Journal of the Neurological Sciences
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
Mónica Tramullas, Raquel Francés, Roberto de la Fuente, Sara Velategui, María Carcelén, Raquel García, Javier Llorca, María A Hurlé
Neuropathic pain is a debilitating chronic syndrome that is often refractory to currently available analgesics. Aberrant expression of several microRNAs (miRNAs) in nociception-related neural structures is associated with neuropathic pain in rodent models. We have exploited the antiallodynic phenotype of mice lacking the bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), a transforming growth factor-β (TGF-β) pseudoreceptor. We used these mice to identify new miRNAs that might be useful for diagnosing, treating, or predicting neuropathic pain...
August 8, 2018: Science Translational Medicine
Hemant Kumar, Hyemin Choi, Min-Jae Jo, Hari Prasad Joshi, Manjunatha Muttigi, Dario Bonanomi, Sung Bum Kim, Eunmi Ban, Aeri Kim, Soo-Hong Lee, Kyoung-Tae Kim, Seil Sohn, Xiang Zeng, Inbo Han
After spinal cord injury (SCI), neutrophil elastase (NE) released at injury site disrupts vascular endothelium integrity and stabilization. Angiopoietins (ANGPTs) are vascular growth factors that play an important role in vascular stabilization. We hypothesized that neutrophil elastase is one of the key determinants of vascular endothelium disruption/destabilization and affects angiopoietins expression after spinal cord injury. To test this, tubule formation and angiopoietins expression were assessed in endothelial cells exposed to different concentrations of recombinant neutropil elastase...
August 7, 2018: Acta Neuropathologica Communications
Sonia Kartha, Christine L Weisshaar, Blythe H Philips, Beth A Winkelstein
Painful neuropathic injuries are accompanied by robust inflammatory and oxidative stress responses that contribute to the development and maintenance of pain. After neural trauma the inflammatory enzyme cyclooxygenase-2 (COX-2) increases concurrent with pain onset. Although pre-treatment with the COX-2 inhibitor, meloxicam, before a painful nerve root compression prevents the development of pain, the pathophysiological mechanisms are unknown. This study evaluated if pre-treatment with meloxicam prior to painful root injury prevents pain by reducing spinal inflammation and peripheral oxidative stress...
August 4, 2018: Neuroscience
Flavien Bessaguet, Aurore Danigo, Hichem Bouchenaki, Mathilde Duchesne, Laurent Magy, Laurence Richard, Franck Sturtz, Alexis Desmouliere, Claire Demiot
Peripheral neuropathy is the major dose limiting side effect of many currently used chemotherapies, such as vincristine (VCR). We recently demonstrated that candesartan, an angiotensin II type 1 receptor antagonist, was neuroprotective against resiniferatoxin-induced sensory neuropathy and that this effect is mediated by stimulation of the angiotensin II type 2 receptor (AT2R). Thus, we evaluated the effect of preventive treatment with candesartan and a specific AT2R agonist, C21, on a mouse model of VCR-induced neuropathy...
August 2, 2018: Pain
Lusine Gomtsian, Kirsty Bannister, Nathan Eyde, Dagoberto Robles, Anthony H Dickenson, Frank Porreca, Edita Navratilova
Modulation of pain may result from engagement of opioid receptors in multiple brain regions. Whether sensory and affective qualities of pain are differentially affected by brain opioid receptor circuits remains unclear. We previously reported that opioid actions within the rostral anterior cingulate cortex (rACC) produces selective modulation of affective qualities of neuropathic pain in rodents but whether such effects may occur in other areas of the anterior cingulate cortex (ACC) is not known. Here, morphine was microinjected in three regions of the ACC or in the rostral ventromedial medulla (RVM) and pain behaviors in naïve, sham or spinal nerve ligated (SNL) rats were evaluated...
August 2, 2018: Pain
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
Margherita Brindisi, Giuseppe Borrelli, Simone Brogi, Alessandro Grillo, Samuele Maramai, Marco Paolino, Mascia Benedusi, Alessandra Pecorelli, Giuseppe Valacchi, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Marco Allarà, Alessia Ligresti, Patrizia Minetti, Giuseppe Campiani, Stefania Butini, Vincenzo di Marzo, Sandra Gemma
The unique role of fatty acid amide hydrolase (FAAH) in terminating endocannabinoid (EC) signaling supports its relevance as therapeutic target. Inhibition of the ECs metabolizing enzymes elicits indirect agonism of CBRs, and therapeutic efficacy, devoid of psychotropic effects. Based on our previous ligands and aiming at discovering new selective FAAH inhibitors, we developed a series of new compounds (5a-l) characterized by functionalized tricyclic scaffolds. All the developed compounds display negligible activity on MAGL and CBRs...
August 7, 2018: ChemMedChem
Corey W Hunter, Dawood Sayed, Timothy Lubenow, Timothy Davis, Jonathan Carlson, Jeffery Rowe, Ralph Justiz, Tory McJunkin, Timothy Deer, Pankaj Mehta, Steven Falowski, Leo Kapural, Jason Pope, Nagy Mekhail
INTRODUCTION: Dorsal root ganglion stimulation (DRGS) is a powerful tool in the treatment of chronic, neuropathic pain. The premise of DRGS is similar to that of conventional spinal cord stimulation (cSCS), however, there is more variability in how it can be utilized. While it is this variability that likely gives it its versatility, DRGS is not as straightforward to implement as cSCS. The purpose of this study was to assess the efficacy of DRGS on a broad number of diagnoses, determine which dorsal root ganglia were associated with better outcomes for particular body parts/diagnoses, and evaluate what factors/parameters were associated with higher rates of trial success...
August 7, 2018: Neuromodulation: Journal of the International Neuromodulation Society
Ya-Feng Zhou, Xiao-Ming Ying, Xiao-Fen He, Sheng-Yun Shou, Jun-Jun Wei, Zhao-Xia Tai, Xiao-Mei Shao, Yi Liang, Fang Fang, Jian-Qiao Fang, Yong-Liang Jiang
Painful diabetic neuropathy (PDN) is a common and troublesome diabetes complication. Protein kinase C (PKC)-mediated dorsal root ganglia (DRG) P2X3 receptor upregulation is one important mechanism underlying PDN. Accumulating evidence demonstrated that electroacupuncture (EA) at low frequency could effectively attenuate neuropathic pain. Our previous study showed that 2-Hz EA could relieve pain well in PDN. The study aimed to investigate whether 2-Hz EA relieves pain in PDN through suppressing PKC-mediated DRG P2X3 receptor upregulation...
August 7, 2018: Purinergic Signalling
Andrew J Shepherd, Aaron D Mickle, Judith P Golden, Madison R Mack, Carmen M Halabi, Annette D de Kloet, Vijay K Samineni, Brian S Kim, Eric G Krause, Robert W Gereau, Durga P Mohapatra
Peripheral nerve damage initiates a complex series of structural and cellular processes that culminate in chronic neuropathic pain. The recent success of a type 2 angiotensin II (Ang II) receptor (AT2R) antagonist in a phase II clinical trial for the treatment of postherpetic neuralgia suggests angiotensin signaling is involved in neuropathic pain. However, transcriptome analysis indicates a lack of AT2R gene ( Agtr2 ) expression in human and rodent sensory ganglia, raising questions regarding the tissue/cell target underlying the analgesic effect of AT2R antagonism...
August 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
Fausto Salaffi, Marco Di Carlo, Marina Carotti, Piercarlo Sarzi-Puttini
BACKGROUND: The presence of neuropatic pain (NeP) is common in subjects with established rheumatoid arthritis (RA), and it can influence the disease remission. These aspects have not been investigated in patients with early rheumatoid arthritis (ERA). OBJECTIVE: To investigate the effect of NeP on the achievement of remission in patients with ERA. METHOD: The study involved consecutive patients with moderately or highly active ERA (a score of >11 on the Simplified Disease Activity Index)...
August 6, 2018: Current Rheumatology Reviews
Liberty François-Moutal, David Donald Scott, Samantha Perez-Miller, Vijay Gokhale, May Khanna, Rajesh Khanna
Drug discovery campaigns directly targeting the voltage-gated sodium channel NaV1.7, a highly prized target in chronic pain, have not yet been clinically successful. In a differentiated approach, we demonstrated allosteric control of trafficking and activity of NaV1.7 by prevention of SUMOylation of collapsin response mediator protein 2 (CRMP2). Spinal administration of a SUMOylation incompetent CRMP2 (CRMP2 K374A) significantly attenuated pain behavior in the spared nerve injury (SNI) model of neuropathic pain, underscoring the importance of SUMOylation of CRMP2 as a pathologic event in chronic pain...
August 6, 2018: Channels
Andrei V Chernov, Albert G Remacle, Swathi K Hullugundi, Piotr Cieplak, Mila Angert, Jennifer Dolkas, Veronica I Shubayev, Alex Y Strongin
Neurotrauma frequently results in neuropathic pain. Our earlier studies revealed that peripheral neurotrauma-induced fragmentation of the myelin basic protein (MBP), a major component of the myelin sheath formed by Schwann cells, initiates a pain response from light touch stimuli (mechanical allodynia) in rodents. Here, we identified the cyclin-dependent kinase 5 (CDK5), as an intracellular interactor of MBP in Schwann cells. The algesic peptide fragment of MBP directly associated with CDK5. When complexed with its p25 co-activator, CDK5 phosphorylated the conserved MBP sequence...
August 6, 2018: FEBS Journal
M A Bangash, Sascha R A Alles, Sonia Santana-Varela, Queensta Millet, Shafaq Sikandar, Larissa de Clauser, Freija Ter Heegde, Abdella M Habib, Vanessa Pereira, Jane E Sexton, Edward C Emery, Shengnan Li, Ana P Luiz, Janka Erdos, Samuel J Gossage, Jing Zhao, James J Cox, John N Wood
Background: Sensory neurons play an essential role in almost all pain conditions, and have recently been classified into distinct subsets on the basis of their transcriptomes. Here we have analysed alterations in dorsal root ganglia (DRG) gene expression using microarrays in mouse models related to human chronic pain. Methods: Six different pain models were studied in male C57BL/6J mice: (1) bone cancer pain using cancer cell injection in the intramedullary space of the femur; (2) neuropathic pain using partial sciatic nerve ligation; (3) osteoarthritis pain using mechanical joint loading; (4) chemotherapy-induced pain with oxaliplatin; (5) chronic muscle pain using hyperalgesic priming; and (6) inflammatory pain using intraplantar complete Freund's adjuvant...
2018: Wellcome Open Research
Keisuke Migita, Yu Matsuzaki, Kohei Koga, Taichi Matsumoto, Kenichi Mishima, Shuji Hara, Kenji Honda
The role of the GABAB receptor in the anterior cingulate cortex (ACC) of neuropathic pain is unclear. Injection of a GABAB receptor antagonist CGP35348 into the ACC induced mechanical hypersensitivity in normal rats. Activation of the GABAB receptor injected by a GABAB receptor agonist baclofen into the ACC attenuated mechanical hypersensitivity in partial sciatic nerve ligation (PSNL) rats. Co-microinjection of CGP35348 with a muscarinic M1 receptor agonist McN-A-343 into the ACC significantly inhibited McN-A-343-induced antihypersensitivity in PSNL rats...
June 2018: Journal of Pharmacological Sciences
Volker M Tronnier, Sam Eldabe, Jörg Franke, Frank Huygen, Philippe Rigoard, Javier de Andres Ares, Richard Assaker, Alejandro Gomez-Rice, Marco La Grua, Maarten Moens, Lieven Moke, Christophe Perruchoud, Nasir A Quraishi, Dominique A Rothenfluh, Pedram Tabatabaei, Koen Van Boxem, Carmen Vleggeert-Lankamp, Björn Zoëga, Herman J Stoevelaar
PURPOSE: Management of patients with persisting pain after spine surgery (PPSS) shows significant variability, and there is limited evidence from clinical studies to support treatment choice in daily practice. This study aimed to develop patient-specific recommendations on the management of PPSS. METHODS: Using the RAND/UCLA appropriateness method (RUAM), an international panel of 6 neurosurgeons, 6 pain specialists, and 6 orthopaedic surgeons assessed the appropriateness of 4 treatment options (conservative, minimally invasive, neurostimulation, and re-operation) for 210 clinical scenarios...
August 4, 2018: European Spine Journal
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