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    Photosensitization of TRPA1 and TRPV1 by 7-dehydrocholesterol: implications for the Smith- Lemli-Opitz syndrome.
    Pain 2017 Sep 1. Epub 2017 Sep 1.
    1 Department of Anatomy, Physiology and Biophysics, Faculty of Biology, University of Bucharest, Romania 2 Institute for Physiology and Pathophysiology, Friedrich-Alexander University of Erlangen- Nürnberg, Germany 3 Department of Pharmacology and Clinical Pharmacy, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania 4 Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
    Loss of function mutations in the enzyme 7-dehydrocholesterol reductase are responsible for the Smith-Lemli-Opitz syndrome, in which 7-dehydrocholesterol (7-DHC) levels are markedly increased in the plasma and tissues of patients. This increase in 7-DHC is probably associated with the painful and itchy photosensitivity reported by the large majority of Smith-Lemli-Opitz syndrome patients. In order to identify the molecular targets involved in the activation and photosensitization of primary afferents by 7-DHC we focused on TRPA1 and TRPV1, two ion channels expressed in nociceptive nerve endings and previously shown to respond to ultraviolet and visible light under pathophysiological circumstances. Read More

    Cannabis constituent synergy in a mouse neuropathic pain model.
    Pain 2017 Sep 1. Epub 2017 Sep 1.
    Pain Management Research Institute, Kolling Institute of Medical Research, Northern Clinical School, University of Sydney at Royal North Shore Hospital, NSW, Australia.
    Cannabis and its psychoactive constituent Δ9-tetrahydrocannabinol (THC) have efficacy against neuropathic pain however, this is hampered by their side-effects. It has been suggested that co-administration with another major constituent cannabidiol (CBD) might enhance the analgesic actions of THC and minimise its deleterious side-effects. We examined the basis for this phytocannabinoid interaction in a mouse chronic constriction injury (CCI) model of neuropathic pain. Read More

    Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis.
    Pain 2017 Sep 1. Epub 2017 Sep 1.
    Departments of Pharmacology and Anaesthesia, Pain Management & Perioperative Medicine, Dalhousie University, 5850 College Street, Halifax, Nova Scotia, B3H 4R2, Canada.
    Osteoarthritis (OA) is a multifactorial joint disease, which includes joint degeneration, intermittent inflammation, and peripheral neuropathy. Cannabidiol (CBD) is a non-euphoria producing constituent of cannabis that has the potential to relieve pain. The aim of this study was to determine if CBD is anti-nociceptive in OA, and whether inhibition of inflammation by CBD could prevent the development of OA pain and joint neuropathy. Read More

    Brain processing of the temporal dimension of acute pain in short-term memory.
    Pain 2017 Oct;158(10):2001-2011
    aDepartment of Neuroscience, Université de Montréal, Montréal, QC, CanadabCentre de recherche de l'Institut universitaire de gériatrie de Montréal, Université de Montréal, Montréal, QC, CanadacDepartment of psychology, McGill University, Montreal, QC, CanadadDepartment of Stomatology, Université de Montréal, Montréal, QC, CanadaeÉcole Polytechnique de Montréal, Montréal, QC, CanadafÉcole de psychologie, Université Laval, Quebec City, QC, CanadagGroupe de recherche sur le système nerveux central (GRSNC), and Centre de recherche en neuropsychologie et cognition (CERNEC), Université de Montréal, Montréal, QC, Canada.
    The dynamics of noxious sensation shapes pain perception, yet the memory of the temporal dimension of pain remains almost completely unexplored. Here, brain activity during the memory of pain duration was contrasted with that associated with the memory of pain intensity using functional magnetic resonance imaging and a delayed reproduction task. Participants encoded, maintained during a short delay, and reproduced (1) the "duration" of pain (ie, onset-to-offset), (2) the "dynamics" of pain (ie, evolution of pain over time), or (3) the intensity of pain (ie, control with no explicit temporal processing required). Read More

    Pain and itch outcome trajectories differ among European American and African American survivors of major thermal burn injury.
    Pain 2017 Aug 3. Epub 2017 Aug 3.
    From the 1Institute for Trauma Recovery (MCM, JS, BL, AVB, AL) 2Anesthesiology, University of North Carolina, Chapel Hill, NC (MCM, SAM, JS, BL, AL) 3Emergency Medicine, University of North Carolina, Chapel Hill, NC (SAM) 4Jaycee Burn Center, University of North Carolina Chapel Hill, NC (SWJ, FW, JH, BAC) 5Washington Hospital Burn Center, Washington, DC (JWS) 6Department of Surgery, University of South Florida, Tampa FL (DJS, RK) 7Departments of Medicine and Biostatistics, University of North Carolina, Chapel Hill, NC.
    Over half of individuals experiencing major thermal burn injury (MThBI) receive an autologous skin graft (autograft), in which skin is removed from a healthy "donor" site and transplanted to the burn site. Persistent pain/itch at the graft site are major causes of suffering and disability in MThBI survivors. African Americans have a higher risk of MThBI, and in other clinical settings African Americans experience a greater burden of pain and itch relative to European Americans. Read More

    Age dependent plasticity in endocannabinoid modulation of pain processing through postnatal development.
    Pain 2017 Aug 1. Epub 2017 Aug 1.
    1School of Life Sciences 2 Centre for Analytical Bioscience, School of Pharmacy, University of Nottingham 3Arthritis Research UK Pain Centre, Nottingham NG7 2UH United Kingdom.
    Significant age and experience-dependent remodelling of spinal and supraspinal neural networks occur resulting in altered pain responses in early life. In adults endogenous opioid peptide and endocannabinoid (ECs) pain control systems exist which modify pain responses but the role they play in acute responses to pain and postnatal neurodevelopment is unknown. Here we have studied the changing role of the ECs in brainstem nuclei essential for the control of nociception from birth to adulthood in both rat and human. Read More

    Spinal microglia are required for long-term maintenance of neuropathic pain.
    Pain 2017 Sep;158(9):1792-1801
    aThe Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada bDepartment of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada cFaculty of Dentistry, McGill University, Montreal, QC, Canada dInstitut universitaire en santé mentale de Québec, QC, Canada eDepartment of Psychiatry and Neuroscience, Université Laval, Québec, QC, Canada.
    While spinal microglia play a role in early stages of neuropathic pain etiology, whether they are useful targets to reverse chronic pain at late stages remains unknown. Here, we show that microglia activation in the spinal cord persists for >3 months following nerve injury in rodents, beyond involvement of proinflammatory cytokine and chemokine signalling. In this chronic phase, selective depletion of spinal microglia in male rats with the targeted immunotoxin Mac1-saporin and blockade of brain-derived neurotrophic factor-TrkB signalling with intrathecal TrkB Fc chimera, but not cytokine inhibition, almost completely reversed pain hypersensitivity. Read More

    Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat.
    Pain 2017 Sep;158(9):1647-1655
    aPain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA bDepartments of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
    Vincristine (VNC) is commonly used to treat pediatric cancers, including the most prevalent childhood malignancy, acute lymphoblastic leukemia. Although clinical evidence suggests that VNC causes peripheral neuropathy in children, the degree to which pediatric chemotherapeutic regimens influence pain sensitivity throughout life remains unclear, in part because of the lack of an established animal model of chemotherapy-induced neuropathic pain during early life. Therefore, this study investigated the effects of VNC exposure between postnatal days (P) 11 and 21 on mechanical and thermal pain sensitivity in the developing rat. Read More

    Propranolol treatment prevents chronic central sensitization induced by repeated dural stimulation.
    Pain 2017 Oct;158(10):2025-2034
    aUniversité Clermont AuvergnebInserm, Neuro-Dol, Clermont-Ferrand, FrancecCHU, Clermont-Ferrand, France.
    Migraine is currently conceptualized as a chronic disease with episodic manifestations. In some patients, migraine attack frequency increases, leading to chronic migraine. Daily preventive therapy is initiated to decrease attack frequency. Read More

    Dose-response study of topical allyl isothiocyanate (mustard oil) as a human surrogate model of pain, hyperalgesia, and neurogenic inflammation.
    Pain 2017 Sep;158(9):1723-1732
    Laboratory of Experimental Cutaneous Pain Research, SMI, Department of Health Science and Technology, School of Medicine, Aalborg University, Aalborg, Denmark.
    Despite being a ubiquitous animal pain model, the natural TRPA1-agonist allyl isothiocyanate (AITC, also known as "mustard oil") has only been sparsely investigated as a potential human surrogate model of pain, sensitization, and neurogenic inflammation. Its dose-response as an algogenic, sensitizing irritant remains to be elucidated in human skin. Three concentrations of AITC (10%, 50%, and 90%) and vehicle (paraffin) were applied for 5 minutes to 3 × 3 cm areas on the volar forearms in 14 healthy volunteers, and evoked pain intensity (visual analog scale 0-100 mm) and pain quality were assessed. Read More

    Placebo effects of a sham opioid solution: a randomized controlled study in patients with chronic low back pain.
    Pain 2017 Oct;158(10):1893-1902
    aDepartment of Anesthesiology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanybDepartment of Spinal Surgery, Schön Klink Hamburg Eilbek, Hamburg, GermanycDepartment of Orthopedics, University Medical Center Hamburg-Eppendorf, Hamburg, GermanydDepartment of Clinical and Cognitive Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, GermanyeDepartment of Psychology, University of Mannheim, Mannheim, Germany.
    This study tested the experimental placebo effect in a group of chronic pain patients. Forty-eight patients having chronic back pain participated in a randomized clinical trial that tested the efficacy of a sham opioid solution (NaCl) compared with an alleged neutral, completely inactive solution (NaCl). We shaped the placebo effect by 2 interventions: verbal instruction and conditioning. Read More

    Child and parent pain catastrophizing and pain from presurgery to 6 weeks postsurgery: examination of cross-sectional and longitudinal actor-partner effects.
    Pain 2017 Oct;158(10):1886-1892
    aLawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON, CanadabChild Health Evaluative Sciences, The Hospital for Sick Children, Toronto, ON, CanadacDepartment of Anesthesia, Pain, and Perioperative Medicine, Dalhousie University, Halifax, NS, CanadadCentre for Pediatric Pain Research, IWK Health Centre, Halifax, NS, CanadaeDepartment of Surgery, Dalhousie University, Halifax, NS, Canada.
    Child and parent pain catastrophizing are reported preoperative risk factors for children's acute and persistent postsurgical pain. This study examined dyadic relations between child and parent pain catastrophizing and child and parent ratings of child pain prior to (M = 4.01 days; "baseline") and following surgery (M = 6. Read More

    Mechanisms of distraction in acute pain perception and modulation.
    Pain 2017 06;158(6):1012-1013
    aLawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON, Canada, bChild Health Evaluative Sciences, The Hospital for Sick Children, Toronto, ON, Canada, cDepartment of Psychology and Neuroscience, Dalhousie University, dCentre for Pediatric Pain Research, IWK Health Centre, eDepartment of Pediatrics, IWK Health Centre, Dalhousie University, fThe Mayday Fund.

    Effects of acute psychological stress on placebo and nocebo responses in a clinically relevant model of visceroception.
    Pain 2017 Aug;158(8):1489-1498
    aInstitute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, Essen, GermanybDepartment of Internal Medicine VI, University Hospital Tuebingen, Tuebingen, Germany.
    There is evidence to suggest a role of emotions in placebo and nocebo effects, but whether acute psychological stress changes the magnitude of placebo or nocebo responses has not been tested. In a clinically relevant model of visceroception, we assessed effects of acute psychological stress on changes in urgency and pain in response to positive or negative treatment suggestions. In 120 healthy volunteers, perceived urge-to-defecate and pain in response to individually calibrated rectal distensions were measured with visual analogue scales during a BASELINE. Read More

    Greater fear of visceral pain contributes to differences between visceral and somatic pain in healthy women.
    Pain 2017 Aug;158(8):1599-1608
    aInstitute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanybClinic for Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanycInstitute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
    This functional magnetic resonance imaging study addressed similarities and differences in behavioral and neural responses to experimental visceral compared with somatic pain stimuli and explored the contribution of fear of pain to differences between pain modalities. In N = 22 healthy women, we assessed blood oxygen level-dependent responses to rectal distensions and cutaneous heat stimuli matched for perceived pain intensity. Fear of pain and pain unpleasantness were assessed before and after scanning. Read More

    Neuropathic pain after chronic nerve constriction may not correlate with chloride dysregulation in mouse trigeminal nucleus caudalis neurons.
    Pain 2017 Jul;158(7):1366-1372
    aDepartment of Anatomy & Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA bProgram in Neuroscience, University of Maryland, Baltimore, MD, USA cDepartment of Endodontics, Prosthodontics, and Operative Surgery, Baltimore College of Dentistry, Baltimore, MD, USA.
    Changes in chloride reversal potential in rat spinal cord neurons have previously been associated with persistent pain in nerve injury and inflammation models. These changes correlate with a decrease in the expression of the potassium chloride transporter, KCC2, and with increases in neuronal excitability. Here, we test the hypothesis that similar changes occur in mice with neuropathic pain induced by chronic constriction injury of the trigeminal infraorbital nerve (CCI-ION). Read More

    Targeting brain-derived neurotrophic factor in the medial thalamus for the treatment of central poststroke pain in a rodent model.
    Pain 2017 Jul;158(7):1302-1313
    Neuroscience, Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan.
    Approximately 7% to 10% of patients develop a chronic pain syndrome after stroke. This chronic pain condition is called central poststroke pain (CPSP). Recent studies have observed an abnormal increase in the secretion of brain-derived neurotrophic factor (BDNF) in spinal cord tissue after spinal cord injury. Read More

    Midazolam as an active placebo in 3 fentanyl-validated nociceptive pain models.
    Pain 2017 Jul;158(7):1264-1271
    aDepartment of Anesthesia, General Intensive Care, and Pain Therapy, Medical University of Vienna, Vienna, Austria bDepartment of Anesthesia, Intensive Care, and Pain Medicine, Wilhelminen Hospital, Vienna, Austria cVienna Human Pain Research Group, Vienna, Austria.
    The use of inactive placebos in early translational trials of potentially analgesic compounds is discouraged because of the side-effect profiles of centrally acting analgesics. Therefore, benzodiazepines are used, although their use has not been validated in this context. Whether benzodiazepines confound the results of acute pain tests is unknown. Read More

    Use of analgesics in young adults as a predictor of health care utilization and pain prevalence: Israel defense forces experience.
    Pain 2017 Jun;158(6):1145-1152
    aIsrael Defense Force Medical Corps, Ramat Gan, Israel bDepartment of Management, Bar-Ilan University, Ramat Gan, Israel cDepartment of Neurology, Soroka University Medical Center, Ben Gurion University of the Negev, Beer-Sheva, Israel.
    Pain evaluation in large community studies is difficult. Analgesics can be a useful tool in estimating pain-related conditions in which analgesic use is highly regulated. In this study, we evaluated analgesics consumption patterns of regular Israel Defense Force soldiers. Read More

    Sickle cell disease: a natural model of acute and chronic pain.
    Pain 2017 Apr;158 Suppl 1:S79-S84
    aDepartment of Pediatrics, Section of Pediatric Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI, USA bChildren's Research Institute of the Children's Hospital of Wisconsin, Milwaukee, WI, USA cDepartment of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.

    Psychophysical and psychological predictors of acute pain after breast surgery differ in patients with and without pre-existing chronic pain.
    Pain 2017 Jun;158(6):1030-1038
    aDepartment of Neurology, University of Munich, Munich, Germany Departments of bAnaesthesiology, Intensive Care and Pain Medicine and cObstetrics and Gynecology, University Hospital Muenster, Muenster, Germany.
    The prediction of acute postoperative pain would be of great clinical advantage, but results of studies investigating possible predictors are inconsistent. Here, we studied the role of a wide variety of previously suggested predictors in 74 patients undergoing breast surgery. Preoperatively, patients filled out the Pain Sensitivity Questionnaire (PSQ) and a set of psychological questionnaires (the Beck Depression Inventory [BDI], State-Trait Anxiety Inventory [STAI], and Pain Catastrophizing Scale [PCS]) and participated in an experimental pain testing session, including assessment of conditioned pain modulation (CPM), temporal summation, and responses to heat, pinprick, and pressure pain. Read More

    Predictors of the transition from acute to persistent musculoskeletal pain in children and adolescents: a prospective study.
    Pain 2017 May;158(5):794-801
    aDepartment of Pediatrics, Institute on Development and Disability, Oregon Health & Science University, Portland, OR, USA bDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA.
    Strategies directed at the prevention of disabling pain have been suggested as a public health priority, making early identification of youth at risk for poor outcomes critical. At present, limited information is available to predict which youth presenting with acute pain are at risk for persistence. The aims of this prospective longitudinal study were to identify biopsychosocial factors in the acute period that predict the transition to persistent pain in youth with new-onset musculoskeletal (MSK) pain complaints. Read More

    Burning pain: axonal dysfunction in erythromelalgia.
    Pain 2017 May;158(5):900-911
    aDepartment of Neurology, Sydney Children's Hospital and School of Women's and Children's Health, University of New South Wales, Sydney, Australia bDepartment of Neurology and Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan cBrain and Mind Centre, The University of Sydney, Sydney, Australia dTranslational Neuroscience Facilities (TNF), Department of Physiology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Randwick, Sydney, Australia.
    Erythromelalgia (EM) is a rare neurovascular disorder characterized by intermittent severe burning pain, erythema, and warmth in the extremities on heat stimuli. To investigate the underlying pathophysiology, peripheral axonal excitability studies were performed and changes with heating and therapy explored. Multiple excitability indices (stimulus-response curve, strength-duration time constant (SDTC), threshold electrotonus, and recovery cycle) were investigated in 23 (9 EMSCN9A+ and 14 EMSCN9A-) genetically characterized patients with EM stimulating median motor and sensory axons at the wrist. Read More

    Does expecting more pain make it more intense? Factors associated with the first week pain trajectories after breast cancer surgery.
    Pain 2017 May;158(5):922-930
    aDivision of Pain Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Finland bBreast Surgery Unit, Comprehensive Cancer Center, University of Helsinki and Helsinki University Hospital, Finland cInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland dDepartment of Public Health, Hjelt Institute, University of Helsinki, Finland.
    The aim of this study was to identify clinical risk factors for unfavorable pain trajectories after breast cancer surgery, to better understand the association between pain expectation, psychological distress, and acute postoperative pain. This prospective study included 563 women treated for breast cancer. Psychological data included questionnaires for depressive symptoms and anxiety. Read More

    Long-lasting antinociceptive effects of green light in acute and chronic pain in rats.
    Pain 2017 Feb;158(2):347-360
    Departments of aAnesthesiology andbPharmacology, College of Medicine, University of Arizona, Tucson, AZ, USA.
    Treatments for chronic pain are inadequate, and new options are needed. Nonpharmaceutical approaches are especially attractive with many potential advantages including safety. Light therapy has been suggested to be beneficial in certain medical conditions such as depression, but this approach remains to be explored for modulation of pain. Read More

    Persistent pain after motor vehicle collision: comparative effectiveness of opioids vs nonsteroidal antiinflammatory drugs prescribed from the emergency department-a propensity matched analysis.
    Pain 2017 Feb;158(2):289-295
    aDepartment of Emergency Medicine, Alpert Medical School of Brown University, Providence, RI, USA Departments of bEpidemiology and cBiostatistics, Brown University, Providence, RI, USA dDepartment of Quantitative Health Science, University of Massachusetts Medical School, Worcester, MA, USA eDepartment of Emergency Medicine, William Beaumont Hospital, Royal Oak, MI, USA fDepartment of Emergency Medicine, Spectrum Health Butterworth Campus, Grand Rapids, MI, USA gDepartment of Emergency Medicine, North Shore University Hospital, Manhasset, NY, USA hDepartment of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA iDepartment of Emergency Medicine, St Joseph Mercy Hospital, Yipsilanti, MI, USA jDepartment of Emergency Medicine, Baystate Medical Center, Springfield, MA, USA Departments of k Emergency Medicine and l Anesthesiology, University of North Carolina, Chapel Hill, NC, USA mTRYUMPH Research Program, University Of North Carolina, Chapel Hill, NC, USA.
    Each year millions of Americans present to the emergency department (ED) for care after a motor vehicle collision (MVC); the majority (>90%) are discharged to home after evaluation. Acute musculoskeletal pain is the norm in this population, and such patients are typically discharged to home with prescriptions for oral opioid analgesics or nonsteroidal antiinflammatory drugs (NSAIDs). The influence of acute pain management on subsequent pain outcomes in this common ED population is unknown. Read More

    Intraoperative ketamine reduces immediate postoperative opioid consumption after spinal fusion surgery in chronic pain patients with opioid dependency: a randomized, blinded trial.
    Pain 2017 Mar;158(3):463-470
    aDepartment of Neuroanesthesiology, Rigshospitalet-Glostrup, Copenhagen University Hospital, Glostrup, Denmark bDepartment of Anesthesiology, Nykoebing Falster Hospital, Nykoebing Falster, Denmark, Copenhagen University Hospital cDepartment of Anesthesiology, Aarhus University Hospital, Aarhus, Denmark dDepartment of Anesthesiology, Bispebjerg Hospital, Copenhagen University Hospital, Copenhagen, Denmark eDepartment of Anesthesiology, Zealand University Hospital Koege, Copenhagen University Hospital, Koege, Denmark.
    Perioperative handling of surgical patients with opioid dependency represents an important clinical problem. Animal studies suggest that ketamine attenuates central sensitization and hyperalgesia and thereby reduces postoperative opioid tolerance. We hypothesized that intraoperative ketamine would reduce immediate postoperative opioid consumption compared with placebo in chronic pain patients with opioid dependency undergoing lumbar spinal fusion surgery. Read More

    Agomelatine: a new opportunity to reduce neuropathic pain-preclinical evidence.
    Pain 2017 Jan;158(1):149-160
    aUniversité Clermont Auvergne, Université d'Auvergne, INSERM UMR 1107 Neuro-Dol Equipe Pharmacologie Fondamentale et Clinique de la Douleur, CHU Clermont-Ferrand Service de Pharmacologie Médicale, Institut Analgesia, Faculté de Médecine, Clermont-Ferrand, France bUniversité Clermont Auvergne, Université d'Auvergne, INSERM UMR 1107 Neuro-Dol Equipe Pharmacologie Fondamentale et Clinique de la Douleur, Institut Analgesia, Faculté de Médecine, Clermont-Ferrand, France cNeuropsychiatry Division, Institut de Recherches Internationales Servier, Suresnes, France.
    Antidepressants are first-line treatments of neuropathic pain but not all these drugs are really effective. Agomelatine is an antidepressant with a novel mode of action, acting as an MT1/MT2 melatonergic receptor agonist and a 5-HT2C receptor antagonist that involves indirect norepinephrine release. Melatonin, serotonin, and norepinephrine have been involved in the pathophysiology of neuropathic pain. Read More

    Genetic variant rs3750625 in the 3'UTR of ADRA2A affects stress-dependent acute pain severity after trauma and alters a microRNA-34a regulatory site.
    Pain 2017 Feb;158(2):230-239
    aTRYUMPH Research Program bDepartment of Anesthesiology, University of North Carolina, Chapel Hill, NC, USA cDepartment of Battlefield Pain Research, Fort Sam, TX, USAISR dForensic Nursing Program, Family Medicine, Cone Health System, Greensboro, NC, USA eDepartment of Emergency Medicine, William Beaumont Hospital, Royal Oak, MI, USA fDepartment of Emergency Medicine, Spectrum Health Butterworth Campus, Grand Rapids, MI, USA gThe Allan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada hDepartment of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA iDepartment of Emergency Medicine, University of North Carolina, Chapel Hill, NC, USA.
    α2A adrenergic receptor (α2A-AR) activation has been shown in animal models to play an important role in regulating the balance of acute pain inhibition vs facilitation after both physical and psychological stress. To our knowledge, the influence of genetic variants in the gene encoding α2A-AR, ADRA2A, on acute pain outcomes in humans experiencing traumatic stress has not been assessed. In this study, we tested whether a genetic variant in the 3'UTR of ADRA2A, rs3750625, is associated with acute musculoskeletal pain (MSP) severity following motor vehicle collision (MVC, n = 948) and sexual assault (n = 84), and whether this influence was affected by stress severity. Read More

    Reduced excitability and impaired nociception in peripheral unmyelinated fibers from Nav1.9-null mice.
    Pain 2017 Jan;158(1):58-67
    aInstitute for Physiology and Pathophysiology, University of Erlangen-Nuremberg, Erlangen, Germany bDepartment of Anesthesiology and Operative Intensive Care, Heidelberg University, Mannheim, Germany cDepartment of Biomedical Science, University of Sheffield, Sheffield, United Kingdom.
    The upregulation of the tetrodotoxin-resistant voltage-gated sodium channel NaV1.9 has previously been associated with inflammatory hyperalgesia. Na1. Read More

    Disproportionate longer-term opioid use among U.S. adults with mood disorders.
    Pain 2016 Nov;157(11):2452-2457
    aDivision of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA bDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
    Adults with mood disorders frequently use prescription opioids. The factors associated with this increased use remain unclear. We used the Medical Expenditure Panel Surveys from 2005 to 2011 to measure the association of mood disorders with new opioid use and the transition to longer-term opioid use for a variety of pain conditions before and after controlling for patient characteristics and clinical disability. Read More

    Agomelatine: a new opportunity to reduce neuropathic pain. Preclinical evidence.
    Pain 2016 Oct 1. Epub 2016 Oct 1.
    a Université Clermont Auvergne, Université d'Auvergne, INSERM UMR 1107 Neuro-Dol Equipe Pharmacologie Fondamentale et Clinique de la Douleur; CHU Clermont-Ferrand Service de Pharmacologie Médicale; Institut Analgesia, Faculté de Médecine, 63000 Clermont-Ferrand, France b Université Clermont Auvergne, Université d'Auvergne, INSERM UMR 1107 Neuro-Dol Equipe Pharmacologie Fondamentale et Clinique de la Douleur ; Institut Analgesia, Faculté de Médecine, 63000 Clermont-Ferrand, France c Neuropsychiatry division, Institut de Recherches Internationales Servier, 92284 Suresnes, France.
    Antidepressants are first-line treatments of neuropathic pain but not all of these drugs are really effective. Agomelatine is an antidepressant with a novel mode of action, acting as a MT1/MT2 melatonergic receptor agonist and a 5-HT2C receptor antagonist that involves indirect noradrenaline release. Melatonin, serotonin and noradrenaline have been involved in the pathophysiology of neuropathic pain. Read More

    Differential expression of systemic inflammatory mediators in amputees with chronic residual limb pain.
    Pain 2017 Jan;158(1):68-74
    Departments of aPharmacology and Cancer Biology and bAnesthesiology, Duke University Medical Center, Durham, NC cDivision of Anesthesiology, Durham Veterans Affairs Medical Center, Durham, NC dDefense and Veterans Center for Integrative Pain Management, Rockville, MD eDepartment of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN Departments of fBiomedical Informatics, gMedicine, and hAnesthesiology, Vanderbilt University Medical Center, Nashville, TN iDepartment of Military Emergency Medicine, Uniformed Services University, Bethesda, MD.
    Chronic postsurgical pain impacts most amputees, with more than half experiencing neuralgic residual limb pain. The transition from normal acute postamputation pain to chronic residual limb pain likely involves both peripheral and central inflammatory mechanisms. As part of the Veterans Integrated Pain Evaluation Research study, we investigated links between systemic inflammatory mediator levels and chronic residual limb pain. Read More

    Hedonic and motivational responses to food reward are unchanged in rats with neuropathic pain.
    Pain 2016 Dec;157(12):2731-2738
    aDepartment of Pharmacology, University of Arizona, Tucson, AZ, USA bNeuroscience Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly and Company, Indianapolis, IN, USA cDepartment of Psychology, University of Arizona, Tucson, AZ, USA.
    Rewards influence responses to acute painful stimuli, but the relationship of chronic pain to hedonic or motivational aspects of reward is not well understood. We independently evaluated hedonic qualities of sweet or bitter tastants and motivation to seek food reward in rats with experimental neuropathic pain induced by L5/6 spinal nerve ligation. Hedonic response was measured by implantation of intraoral catheters to allow passive delivery of liquid solutions, and "liking/disliking" responses were scored according to a facial reactivity scale. Read More

    Angiotensin-(1-7)/Mas receptor as an antinociceptive agent in cancer-induced bone pain.
    Pain 2016 Dec;157(12):2709-2721
    aDepartment of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USA bDepartment of Physiology, Evelyn McKnight Brain Institute, College of Medicine, University of Arizona, Tucson, AZ, USA.
    Many cancerous solid tumors metastasize to the bone and induce pain (cancer-induced bone pain [CIBP]). Cancer-induced bone pain is often severe because of enhanced inflammation, rapid bone degradation, and disease progression. Opioids are prescribed to manage this pain, but they may enhance bone loss and increase tumor proliferation, further compromising patient quality of life. Read More

    The effect of pain on task switching: pain reduces accuracy and increases reaction times across multiple switching paradigms.
    Pain 2016 Oct;157(10):2179-93
    aMathematics Education Centre, School of Science, Loughborough University, Loughborough, United Kingdom, bCentre for Pain Research, University of Bath, Bath, United Kingdom.
    Pain disrupts attention, which may have negative consequences for daily life for people with acute or chronic pain. It has been suggested that switching between tasks may leave us particularly susceptible to pain-related attentional disruption, because we need to disengage our attention from one task before shifting it onto another. Switching tasks typically elicit lower accuracies and/or longer reaction times when participants switch to a new task compared with repeating the same task, and pain may exacerbate this effect. Read More

    Discriminative ability of reflex receptive fields to distinguish patients with acute and chronic low back pain.
    Pain 2016 Dec;157(12):2664-2671
    aUniversity Clinic of Anesthesiology and Pain Medicine, Inselspital Bern, Bern, Switzerland bInstitute of Social and Preventive Medicine, University of Bern, Bern, Switzerland cDepartment of Health Science and Technology, Center for Sensory-Motor Interaction, Aalborg University, Aalborg, Denmark dDepartment of Radiology, Balgrist University Hospital, Zürich, Switzerland eDepartment of Orthopedics, Private Clinic Sonnenhof, Bern, Switzerland fDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA gInstitute of Primary Health Care, University of Bern, Bern, Switzerland hApplied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
    Low back pain has a life time prevalence of 70% to 85%. Approximately 10% to 20% of all patients experience recurrent episodes or develop chronic low back pain. Sociodemographic, clinical, and psychological characteristics explain the transition from acute to chronic low back pain only to a limited extent. Read More

    Electroencephalographic signatures of pain and analgesia in rats.
    Pain 2016 Oct;157(10):2330-40
    aDepartment of Neurosurgery, Rhode Island Hospital, Providence, RI, USA bDepartment of Neuroscience, Brown University, Providence, RI, USA cDepartment of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
    Pain modulates rhythmic neuronal activity recorded by Electroencephalography (EEG) in humans. Our laboratory previously showed that rat models of acute and neuropathic pain manifest increased power in primary somatosensory cortex (S1) recorded by electrocorticography (ECoG). In this study, we hypothesized that pain increases EEG power and corticocortical coherence in different rat models of pain, whereas treatments with clinically effective analgesics reverse these changes. Read More

    Reduced thermal sensitivity and increased opioidergic tone in the TASTPM mouse model of Alzheimer's disease.
    Pain 2016 Oct;157(10):2285-96
    Wolfson Centre for Age Related Diseases, King's College London, London, United Kingdom.
    Individuals with Alzheimer's disease (AD) are in susceptible patient groups in which pain is an important clinical issue that is often underdiagnosed. However, it is unclear whether decreased pain complaints in patients with AD result from elevated pain tolerance or an impaired ability to communicate sensations. Here, we explored if AD-related pathology is present in key regions of the pain pathway and assessed whether nociceptive thresholds to acute noxious stimulation are altered in the double-mutant APPswe × PS1. Read More

    Restraint training for awake functional brain scanning of rodents can cause long-lasting changes in pain and stress responses.
    Pain 2016 08;157(8):1761-72
    Laboratory of Pain and Integrative Neuroscience, National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD, USA.
    With the increased interest in longitudinal brain imaging of awake rodents, it is important to understand both the short-term and long-term effects of restraint on sensory and emotional processing in the brain. To understand the effects of repeated restraint on pain behaviors and stress responses, we modeled a restraint protocol similar to those used to habituate rodents for magnetic resonance imaging scanning, and studied sensory sensitivity and stress hormone responses over 5 days. To uncover lasting effects of training, we also looked at responses to the formalin pain test 2 weeks later. Read More

    Therapeutic potential of RQ-00311651, a novel T-type Ca2+ channel blocker, in distinct rodent models for neuropathic and visceral pain.
    Pain 2016 08;157(8):1655-65
    aLaboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University (formerly known as Kinki University), Higashi-Osaka, Japan bDepartment of Life Science, Faculty of Science and Engineering, Kindai University (formerly known as Kinki University), Higashi-Osaka, Japan cDepartment of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka, Japan.
    T-type Ca channels (T channels), particularly Cav3.2 among the 3 isoforms, play a role in neuropathic and visceral pain. We thus characterized the effects of RQ-00311651 (RQ), a novel T-channel blocker, in HEK293 cells transfected with human Cav3. Read More

    Complex regional pain syndrome: evidence for warm and cold subtypes in a large prospective clinical sample.
    Pain 2016 08;157(8):1674-81
    aDepartment of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN, USA bDepartment of Neurology, General Fürth Hospital, Fürth, Germany cDepartment of Pain Management, Cleveland Clinic, Cleveland, OH, USA dDepartment of Anesthesiology, VU University Medical Center and EMGO+ Institute for Health and Care Research, Amsterdam, the Netherlands eDepartment of Rehabilitation Medicine, Reuth Rehabilitation Hospital, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel fDepartment of Physical Medicine and Rheumatology, Balgrist University Hospital, Zurich, Switzerland gDepartment of Neurology, University Medical Center Mainz, Mainz, Germany hDepartment of Anesthesiology, Perioperative, and Pain Medicine, Stanford University Medical Center, Stanford, CA, USA iDepartment of Physical Medicine and Rehabilitation, University of Toronto, Toronto, Canada jDepartment of Physical Medicine and Rehabilitation, Northwestern University School of Medicine, Chicago, IL, USA.
    Limited research suggests that there may be Warm complex regional pain syndrome (CRPS) and Cold CRPS subtypes, with inflammatory mechanisms contributing most strongly to the former. This study for the first time used an unbiased statistical pattern recognition technique to evaluate whether distinct Warm vs Cold CRPS subtypes can be discerned in the clinical population. An international, multisite study was conducted using standardized procedures to evaluate signs and symptoms in 152 patients with clinical CRPS at baseline, with 3-month follow-up evaluations in 112 of these patients. Read More

    The effect of local vs remote experimental pain on motor learning and sensorimotor integration using a complex typing task.
    Pain 2016 08;157(8):1682-95
    Faculty of Health Sciences, University of Ontario Institute of Technology, Oshawa, ON, Canada.
    Recent work demonstrated that capsaicin-induced acute pain improved motor learning performance; however, baseline accuracy was very high, making it impossible to discern the impact of acute pain on motor learning and retention. In addition, the effects of the spatial location of capsaicin application were not explored. Two experiments were conducted to determine the interactive effects of acute pain vs control (experiment 1) and local vs remote acute pain (experiment 2) on motor learning and sensorimotor processing. Read More

    Acute analgesic effects of nicotine and tobacco in humans: a meta-analysis.
    Pain 2016 07;157(7):1373-81
    aDepartment of Psychology, Syracuse University, Syracuse, NY, USA bCenter for Integrated Healthcare, Syracuse VA Medical Center, Syracuse, NY, USA cDepartment of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Columbia, SC, USA.
    Although animal models have consistently demonstrated acute pain inhibitory effects of nicotine and tobacco, human experimental studies have yielded mixed results. The main goal of this meta-analysis was to quantify the effects of nicotine/tobacco administration on human experimental pain threshold and tolerance ratings. A search of PubMed and PsycINFO online databases identified 13 eligible articles, including k = 21 tests of pain tolerance (N = 393) and k = 15 tests of pain threshold (N = 339). Read More

    (S)-lacosamide inhibition of CRMP2 phosphorylation reduces postoperative and neuropathic pain behaviors through distinct classes of sensory neurons identified by constellation pharmacology.
    Pain 2016 07;157(7):1448-63
    aDepartment of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USA bDepartment of Biological Chemistry, University of Science and Technology and Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea cDepartment of Biology, University of Utah, Salt Lake City, UT, USA.
    Chronic pain affects the life of millions of people. Current treatments have deleterious side effects. We have advanced a strategy for targeting protein interactions which regulate the N-type voltage-gated calcium (CaV2. Read More

    Relieving patients' pain with expectation interventions: a meta-analysis.
    Pain 2016 06;157(6):1179-91
    aUnit Health, Medical and Neuropsychology, Leiden University, Leiden, the Netherlands bLeiden Institute for Brain and Cognition, Leiden University, Leiden, the Netherlands cDepartment of Psychology and Behavioural Sciences, Aarhus University, Aarhus, Denmark dDanish Pain Research Center, Aarhus University Hospital, Aarhus, Denmark eRadboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands fDepartment of Clinical Psychological Science, Maastricht University, Maastricht, the Netherlands gDepartment of Medical Psychology, Radboud University Medical Center, Nijmegen, the Netherlands.
    Patients' expectations are important predictors of the outcome of analgesic treatments, as demonstrated predominantly in research on placebo effects. Three commonly investigated interventions that have been found to induce expectations (verbal suggestion, conditioning, and mental imagery) entail promising, brief, and easy-to-implement adjunctive procedures for optimizing the effectiveness of analgesic treatments. However, evidence for their efficacy stems mostly from research on experimentally evoked pain in healthy samples, and these findings might not be directly transferable to clinical populations. Read More

    Experimental manipulations of pain catastrophizing influence pain levels in patients with chronic pain and healthy volunteers.
    Pain 2016 Jun;157(6):1287-96
    aDepartment of Psychology and Behavioural Sciences, Aarhus University, Aarhus, Denmark bDanish Pain Research Center, Aarhus University Hospital, Aarhus, Denmark cResearch Department, Spinal Cord Injury Center of Western Denmark, Department of Neurology, Regional Hospital of Viborg, Viborg, Denmark dDepartment of Oncology, Aarhus University Hospital, Aarhus, Denmark eSection of Orofacial Pain and Jaw Function, School of Dentistry, Aarhus University, Aarhus, Denmark fDepartment of Dental Medicine, Karolinska Institutet, Huddinge, Sweden.
    Pain catastrophizing (PC) has been related to pain levels in both patients experiencing acute or chronic pain and in healthy volunteers exposed to experimental pain. Still, it is unclear whether high levels of pain catastrophizing lead to high levels of pain or vice versa. We therefore tested whether levels of pain catastrophizing could be increased and decreased in the same participant through hypnotic suggestions and whether the altered level of situation-specific pain catastrophizing was related to increased and decreased pain levels, respectively. Read More

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