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Injury chronic pain

Kelly Barbosa Gama, Dourivaldo Silva Santos, Afrânio Ferreira Evangelista, Daniela Nascimento Silva, Adriano Costa de Alcântara, Ricardo Ribeiro Dos Santos, Milena Botelho Pereira Soares, Cristiane Flora Villarreal
Neuropathic pain is a type of chronic pain caused by injury or dysfunction of the nervous system, without effective therapeutic approaches. Mesenchymal stromal cells (MSCs), through their paracrine action, have great potential in the treatment of this syndrome. In the present study, the therapeutic potential of MSC-derived conditioned medium (CM) was investigated in a mouse model of neuropathic pain induced by partial sciatic nerve ligation (PSL). PSL mice were treated by endovenous route with bone marrow-derived MSCs (1 × 106 ), CM, or vehicle...
2018: Stem Cells International
Ji Eun Kim, Da-Hyun Song, Soo Hyun Kim, Youngmee Jung, Sang Jun Kim
Osteoarthritis (OA) is characterized by a progressive loss of articular cartilage, subchondral bone sclerosis and synovial inflammation and is the most common chronic condition worldwide today. However, most treatments have focused on pain relief and OA symptoms. For these reasons, many ongoing studies are currently trying to develop efficient and successful therapies based on its pathology. Animal models that mimic the histopathology and symptoms of OA have a critical role in OA research and make it possible to investigate both secondary osteoarthritic changes due to a precedent event such as traumatic injury and naturally occurring changes for the development of therapeutics which can be tested in preclinical and clinical OA trials...
2018: PloS One
Pini Koplovitch, Marshall Devor
Ectopic impulse discharge (ectopia) generated in the soma of afferent neurons in dorsal root ganglia (DRGs) following nerve injury is thought to be a major contributor to neuropathic pain. The DRG is thus a prime interventional target. The process of electrogenesis (impulse generation) in the DRG is far more sensitive to systemically administered Na channel blockers than the process of impulse propagation along sensory axons. It should therefore be possible to selectively suppress DRG ectopia with local application of membrane stabilizing agents without blocking normal impulse traffic...
March 12, 2018: Pain
Guan Yun Frances Wang, Xiang Qun Shi, Wenjia Wu, Maria Gueorguieva, Mu Yang, Ji Zhang
Temporomandibular disorder (TMD) is a set of heterogeneous musculoskeletal conditions involving the temporomandibular joint (TMJ) and/or the masticatory muscles. Up to 33% of the population has had at least one symptom of TMD with 5-10% of them requiring treatment. Common symptoms include limited jaw movement, joint sound, and pain in the orofacial area. Once TMD becomes chronic, it can be debilitating with comorbidities that greatly reduce one's overall quality of life. However, the underlying mechanism of TMD is unclear due to the multicausative nature of the disease...
March 12, 2018: Pain
Cyril Rivat, Chamroeun Sar, Ilana Mechaly, Jean-Philippe Leyris, Lucie Diouloufet, Corinne Sonrier, Yann Philipson, Olivier Lucas, Sylvie Mallié, Antoine Jouvenel, Adrien Tassou, Henri Haton, Stéphanie Venteo, Jean-Philippe Pin, Eric Trinquet, Fabienne Charrier-Savournin, Alexandre Mezghrani, Willy Joly, Julie Mion, Martine Schmitt, Alexandre Pattyn, Frédéric Marmigère, Pierre Sokoloff, Patrick Carroll, Didier Rognan, Jean Valmier
Peripheral neuropathic pain (PNP) is a debilitating and intractable chronic disease, for which sensitization of somatosensory neurons present in dorsal root ganglia that project to the dorsal spinal cord is a key physiopathological process. Here, we show that hematopoietic cells present at the nerve injury site express the cytokine FL, the ligand of fms-like tyrosine kinase 3 receptor (FLT3). FLT3 activation by intra-sciatic nerve injection of FL is sufficient to produce pain hypersensitivity, activate PNP-associated gene expression and generate short-term and long-term sensitization of sensory neurons...
March 12, 2018: Nature Communications
Peter M Grace, Xiaohui Wang, Keith A Strand, Michael V Baratta, Yingning Zhang, Erika L Galer, Hang Yin, Steven F Maier, Linda R Watkins
The absence of selective pharmacological tools is a major barrier to the in vivo study of microglia. To address this issue, we developed a Gq - and Gi -coupled Designer Receptor Exclusively Activated by a Designer Drug (DREADD) to enable selective stimulation or inhibition of microglia, respectively. DREADDs under a CD68 (microglia/macrophage) promoter were intrathecally transfected via an AAV9 vector. Naïve male rats intrathecally transfected with Gq (stimulatory) DREADDs exhibited significant allodynia following intrathecal administration of the DREADD-selective ligand clozapine-N-oxide (CNO), which was abolished by intrathecal interleukin-1 receptor antagonist...
March 9, 2018: Experimental Neurology
Jenny L Wilkerson, Zachary A Curry, Pamela D Kinlow, Brittany L Mason, Ku-Lung Hsu, Mario van der Stelt, Benjamin F Cravatt, Aron H Lichtman
A great need exists for the identification of new effective analgesics to treat sustained pain. However, most preclinical nociceptive assays measure behavioral responses evoked by noxious stimuli (i.e., pain-stimulated behavior), which presents a challenge to distinguish between motor impairing and antinociceptive effects of drugs. Here, we demonstrate that chronic constriction injury of the sciatic nerve (CCI) elicits common pain-stimulated responses (i.e., mechanical allodynia and thermal hyperalgesia) as well as reduces marble burying/digging behaviors that occur during the early stages of the neuropathy and resolve within one week...
March 8, 2018: Pain
Shannon M Blakey, H Ryan Wagner, Jennifer Naylor, Mira Brancu, Ilana Lane, Meghann Sallee, Nathan A Kimbrel, Eric B Elbogen
The polytrauma clinical triad refers to the co-occurrence of chronic pain, traumatic brain injury (TBI), and posttraumatic stress disorder (PTSD). Despite research implicating dyadic relationships between these conditions and adverse outcomes, scant research has examined the polytrauma clinical triad's relation to suicide or violence. The present cross-sectional study was designed to examine whether this complex clinical presentation increases risk of suicidal ideation and violent impulses after accounting for other established risk factors...
March 8, 2018: Journal of Pain: Official Journal of the American Pain Society
Okihiro Onishi, Kazuya Ikoma, Ryo Oda, Tetsuro Yamazaki, Hiroyoshi Fujiwara, Shunji Yamada, Masaki Tanaka, Toshikazu Kubo
Although treatment protocols are available, patients experience both acute neuropathic pain and chronic neuropathic pain, hyperalgesia, and allodynia after peripheral nerve injury. The purpose of this study was to identify the brain regions activated after peripheral nerve injury using functional magnetic resonance imaging (fMRI) sequentially and assess the relevance of the imaging results using histological findings. To model peripheral nerve injury in male Sprague-Dawley rats, the right sciatic nerve was crushed using an aneurysm clip, under general anesthesia...
March 7, 2018: Neuroscience Letters
Meritxell Llorca-Torralba, Juan A Mico, Esther Berrocoso
The persistent activation of N-methyl-d-aspartate acid receptors (NMDARs) seems to be responsible for a series of changes in neurons associated with neuropathic pain, including the failure of opioids that act through mu-opioid receptors (MORs) to provide efficacious pain relief. As the noradrenergic locus coeruleus (LC) forms part of the endogenous analgesic system, we explored how intra-LC administration of morphine, a MORs agonist, alone or in combination with MK-801, a NMDARs antagonist, affects the sensorial and affective dimension of pain in a rat model of neuropathic pain; chronic constriction injury (CCI)...
March 7, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Aroon La-Up, Phongtape Wiwatanadate, Sureeporn Uthaikhup, Sakda Pruenglampoo
Cadmium exposure is known to cause adverse health effects in different organs of the human body but whether the effects result in chronic musculoskeletal pain (CMP) remain inclusive. The present study, therefore, aims to examine the relationship between urinary cadmium levels and CMP. An observational retrospective cohort study was conducted in two areas having different levels of cadmium contamination for comparison. The subjects enrolled into the study were individuals ages 18 and above who have lived in the studied areas for 1 year or more...
March 9, 2018: Environmental Science and Pollution Research International
Dilara Nemutlu Samur, Rana Arslan, Sule Aydın, Nurcan Bektas
The purpose of this study is to assess the possible anti-allodynic and antihyperalgesic effect of valnoctamide, an amide derivative of valproic acid, at the doses of 40, 70 and 100mg/kg (i.p.) in neuropathic pain model induced by chronic constriction injury in rats, by using dynamic plantar test and plantar test (Hargreaves method), and to evaluate that the possible role of certain serotonin, noradrenergic, opioid and GABAergic receptors by pre-treatment with 1mg/kg (i.p.) ketanserin, yohimbine, naloxone and 0...
March 6, 2018: European Journal of Pharmacology
Gunnar Poplawski, Tetsuhiro Ishikawa, Coralie Brifault, Corinne Lee-Kubli, Robert Regestam, Kenneth W Henry, Yasuhiro Shiga, HyoJun Kwon, Seiji Ohtori, Steven L Gonias, Wendy M Campana
Sensory neurons in the PNS demonstrate substantial capacity for regeneration following injury. Recent studies have identified changes in the transcriptome of sensory neurons, which are instrumental for axon regeneration. The role of Schwann cells (SCs) in mediating these changes remains undefined. We tested the hypothesis that SCs regulate expression of genes in sensory neurons before and after PNS injury by comparing mice in which LDL Receptor-related Protein-1 (LRP1) is deleted in SCs (scLRP1-/- mice) with wild-type (scLRP1+/+ ) littermates...
March 9, 2018: Glia
Jelena M Janjic, Kiran Vasudeva, Muzamil Saleem, Andrea Stevens, Lu Liu, Sravan Patel, John A Pollock
Neuroinflammation involving macrophages elevates Prostaglandin E2 , associated with neuropathic pain. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) inhibits cyclooxygenase, reducing PGE2 . However, NSAIDs cause physiological complications. We developed nanoemulsions incorporating celecoxib and near infrared dye. Intravenous injected nanoemulsion is incorporated into monocytes that accumulate at the injury; revealed in live animals by fluorescence. A single dose (celecoxib 0.24 mg/kg) provides targeted delivery in chronic constriction injury rats, resulting in significant reduction in the visualized inflammation, infiltration of macrophages, COX-2 and PGE2 ...
February 25, 2018: Journal of Neuroimmunology
Stephen A Harrison, Mary E Rinella, Manal F Abdelmalek, James F Trotter, Angelo H Paredes, Hays L Arnold, Marcelo Kugelmas, Mustafa R Bashir, Mark J Jaros, Lei Ling, Stephen J Rossi, Alex M DePaoli, Rohit Loomba
BACKGROUND: Non-alcoholic steatohepatitis is a chronic liver disease characterised by the presence of hepatic steatosis, inflammation, and hepatocellular injury, for which no Food and Drug Administration (FDA)-approved treatment exists. FGF19 is a hormone that regulates bile acid synthesis and glucose homoeostasis. We aimed to assess the safety and efficacy of NGM282, an engineered FGF19 analogue, for the treatment of non-alcoholic steatohepatitis. METHODS: In this randomised, double-blind, placebo-controlled, phase 2 study, we recruited patients aged 18-75 years with biopsy-confirmed non-alcoholic steatohepatitis as defined by the non-alcoholic steatohepatitis clinical research network histological scoring system, from hospitals and gastroenterology and liver clinics in Australia and the USA...
March 5, 2018: Lancet
Athir Morad, Salia Farrokh, Alexander Papangelou
PURPOSE OF REVIEW: Pain management in neurocritical care is a subject often avoided because of concerns over the side-effects of analgesics and the potential to cause additional neurological injury with treatment. The sedation and hypercapnia caused by opioids have been feared to mask the neurological examination and contribute to elevations in intracranial pressure. Nevertheless, increasing attention to patient satisfaction has sparked a resurgence in pain management. As opioids have remained at the core of analgesic therapy, the increasing attention to pain has contributed to a growing epidemic of opioid dependence...
April 2018: Current Opinion in Critical Care
Lisa M Betthauser, Lisa A Brenner, Wesley Cole, Ann I Scher, Karen Schwab, Brian J Ivins
OBJECTIVE: Service members are frequently diagnosed with comorbid mild traumatic brain injury (mTBI) and posttraumatic stress disorder after returning from Afghanistan and Iraq. Little is known about how mTBI in the postacute and chronic phases combined with current posttraumatic stress disorder symptoms (PTS) affects performance on the Automated Neuropsychological Assessment Metrics, Version 4, Traumatic Brain Injury-Military (ANAM4) battery used by the US military. We examined postdeployment ANAM4 performance using conventional statistical methods, as well as rates of poor performance, below established cutoffs (<10th and ≤2nd percentile)...
March 2018: Journal of Head Trauma Rehabilitation
Petr Dubový, Ilona Klusáková, Ivana Hradilová-Svíženská, Marek Joukal, Pere Boadas-Vaello
Peripheral nerve injuries (PNIs) may result in cellular and molecular changes in supraspinal structures possibly involved in neuropathic pain (NPP) maintenance. Activated glial cells in specific supraspinal subregions may affect the facilitatory role of descending pathways. Sterile chronic compression injury (sCCI) and complete sciatic nerve transection (CSNT) in rats were used as NPP models to study the activation of glial cells in the subregions of periaqueductal gray (PAG) and rostral ventromedial medulla (RVM)...
2018: Frontiers in Cellular Neuroscience
Raymond Leung, Panos Thomas
Osteochondral defects (OCD) are rare conditions that usually present in young adolescents. The causes include trauma, inflammation, ischaemia, genetics and changes at secondary ossification centres. The case report presents a 27-year-old man with chronic intermittent left knee pain for about 3 years. He typically develops the symptom after prolonged standing or when rising from a prolonged seated position. An initial MRI scan in 2014 did not identify and report an OCD that was present in his left lateral tibial plateau...
March 7, 2018: BMJ Case Reports
A P K Riffel, M C Q Santos, J A de Souza, T Scheid, A Horst, C Kolberg, A Belló-Klein, W A Partata
Vitamin E (vit. E) and vitamin C (vit. C) are antioxidants that inhibit nociception. The effect of these vitamins on oxidative-stress markers in the spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve is unknown. This study investigated the effect of intraperitoneal administration of vit. E (15 mg·kg-1·day-1) and vit. C (30 mg·kg-1·day-1), given alone or in combination, on spinal cord oxidative-stress markers in CCI rats. Adult male Wistar rats weighing 200-250 g were divided equally into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve), which received injections of vitamins or vehicle (saline containing 1% Tween 80) for 3 or 10 days (n=6/each group)...
March 1, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
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