WorldWideScience

Sample records for human experimental pain

  1. [Pain in humans: experimental facts and hypotheses].

    Science.gov (United States)

    Cesaro, P

    1994-09-15

    The description of painful phenomena in humans has to take into account its different components: sensory component (relevant to nociception), affective and emotional components. Nociceptor's (physiology is best understood with electrophysiological and neurochemical methods allowing a clear description of hyperalgesia, with its peripheral and spinal mechanisms. A functional model is partly available to explain allodynia, spontaneous burning pain and lightning pain, the three main consequences following deafferentation. At the thalamo-cortical level, one can describe nociceptive pathways and other pathways or neuronal networks involved in the affective and emotional components of pain.

  2. A human experimental model of episodic pain

    DEFF Research Database (Denmark)

    Petrini, Laura; Hennings, Kristian; Li, Xi

    2014-01-01

    (VRS). Physiological (blood flow and axon flare reflex), psychophysical (perception threshold and verbal pain ratings) and electrophysiological (128 channels recorded somatosensory evoked potential (SEP)) measurements were recorded. The stimulation evoked a visible axon flare reflex and caused...

  3. Mechanisms of Osteoarthritic Pain. Studies in Humans and Experimental Models

    Directory of Open Access Journals (Sweden)

    Annett Eitner

    2017-11-01

    Full Text Available Pain due to osteoarthritis (OA is one of the most frequent causes of chronic pain. However, the mechanisms of OA pain are poorly understood. This review addresses the mechanisms which are thought to be involved in OA pain, derived from studies on pain mechanisms in humans and in experimental models of OA. Three areas will be considered, namely local processes in the joint associated with OA pain, neuronal mechanisms involved in OA pain, and general factors which influence OA pain. Except the cartilage all structures of the joints are innervated by nociceptors. Although the hallmark of OA is the degradation of the cartilage, OA joints show multiple structural alterations of cartilage, bone and synovial tissue. In particular synovitis and bone marrow lesions have been proposed to determine OA pain whereas the contribution of the other pathologies to pain generation has been studied less. Concerning the peripheral neuronal mechanisms of OA pain, peripheral nociceptive sensitization was shown, and neuropathic mechanisms may be involved at some stages. Structural changes of joint innervation such as local loss and/or sprouting of nerve fibers were shown. In addition, central sensitization, reduction of descending inhibition, descending excitation and cortical atrophies were observed in OA. The combination of different neuronal mechanisms may define the particular pain phenotype in an OA patient. Among mediators involved in OA pain, nerve growth factor (NGF is in the focus because antibodies against NGF significantly reduce OA pain. Several studies show that neutralization of interleukin-1β and TNF may reduce OA pain. Many patients with OA exhibit comorbidities such as obesity, low grade systemic inflammation and diabetes mellitus. These comorbidities can significantly influence the course of OA, and pain research just began to study the significance of such factors in pain generation. In addition, psychologic and socioeconomic factors may aggravate

  4. Experimental human pain models in gastro-esophageal reflux disease and unexplained chest pain

    Institute of Scientific and Technical Information of China (English)

    Asbj(φ)rn Mohr Drewes; Lars Arendt-Nielsen; Peter Funch-Jensen; Hans Gregersen

    2006-01-01

    Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechanical, electrical, thermal and chemical methods in visceral pain research are discussed with emphasis of combinations (e.g., the multimodal approach). The methods have been used widely in assessment of pain mechanisms in the esophagus and have contributed to our understanding of the symptoms reported in these patients. Hence abnormal activation and plastic changes of central pain pathways seem to play a major role in the symptoms in some patients with gastro-esophageal reflux disease and in patients with functional chest pain of esophageal origin. These findings may lead to an alternative approach for treatment in patients that does not respond to conventional medical or surgical therapy.

  5. Experimental human pain models in gastro-esophageal reflux disease and unexplained chest pain

    Science.gov (United States)

    Drewes, Asbjørn Mohr; Arendt-Nielsen, Lars; Funch-Jensen, Peter; Gregersen, Hans

    2006-01-01

    Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechanical, electrical, thermal and chemical methods in visceral pain research are discussed with emphasis of combinations (e.g., the multimodal approach). The methods have been used widely in assessment of pain mechanisms in the esophagus and have contributed to our understanding of the symptoms reported in these patients. Hence abnormal activation and plastic changes of central pain pathways seem to play a major role in the symptoms in some patients with gastro-esophageal reflux disease and in patients with functional chest pain of esophageal origin. These findings may lead to an alternative approach for treatment in patients that does not respond to conventional medical or surgical therapy. PMID:16718803

  6. Human experimental pain models: A review of standardized methods in drug development

    Directory of Open Access Journals (Sweden)

    K. Sunil kumar Reddy

    2012-01-01

    Full Text Available Human experimental pain models are essential in understanding the pain mechanisms and appear to be ideally suited to test analgesic compounds. The challenge that confronts both the clinician and the scientist is to match specific treatments to different pain-generating mechanisms and hence reach a pain treatment tailored to each individual patient. Experimental pain models offer the possibility to explore the pain system under controlled settings. Standardized stimuli of different modalities (i.e., mechanical, thermal, electrical, or chemical can be applied to the skin, muscles, and viscera for a differentiated and comprehensive assessment of various pain pathways and mechanisms. Using a multimodel-multistructure testing, the nociception arising from different body structures can be explored and modulation of specific biomarkers by new and existing analgesic drugs can be profiled. The value of human experimental pain models is to link animal and clinical pain studies, providing new possibilities for designing successful clinical trials. Spontaneous pain, the main compliant of the neuropathic patients, but currently there is no human model available that would mimic chronic pain. Therefore, current human pain models cannot replace patient studies for studying efficacy of analgesic compounds, although being helpful for proof-of-concept studies and dose finding.

  7. The genetic influences on oxycodone response characteristics in human experimental pain

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Sato, Hiroe; Nielsen, Lecia M

    2015-01-01

    Human experimental pain studies are of value to study basic pain mechanisms under controlled conditions. The aim of this study was to investigate whether genetic variation across selected mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1and OPRD1, respectively) influenced analgesic respon......; therefore, variation in opioid receptor genes may partly explain responder characteristics to oxycodone....

  8. The hypoalgesic effect of oxycodone in human experimental pain models in relation to the CYP2D6 oxidation polymorphism

    DEFF Research Database (Denmark)

    Zwisler, Stine T; Enggaard, Thomas P; Noehr-Jensen, Lene

    2009-01-01

    , extensive metabolizers (EM). The objective of the study was to determine if the analgesic effect of oxycodone in human experimental pain depends on its metabolism to oxymorphone. The analgesic effect of oxycodone was evaluated in a randomized, placebo-controlled, double-blinded, crossover experiment...... including 33 (16 EM and 17 PM) healthy volunteers. Pain tests were performed before and 1, 2, 3 and 4 hr after medication and included pain detection and tolerance thresholds to single electrical sural nerve stimulation, pain summation threshold to repetitive electrical sural nerve stimulation and the cold...... pressor test with rating of discomfort and pain-time area under curve (AUC(0-2 min.)). For single sural nerve stimulation, there was a less pronounced increase in thresholds on oxycodone in pain detection (9% vs. 20%, P = 0.02, a difference of 11%, CI: 2%-20%) and pain tolerance thresholds (15% vs. 26%, P...

  9. Inflammatory pain in experimental burns in man

    DEFF Research Database (Denmark)

    Pedersen, J L

    2000-01-01

    stimuli may be more reproducible. A methodological study also demonstrated that habituation to experimental pain developed as the study proceeded. Habituation is common in experimental pain models, and dividing analgesics and placebo evenly between the study days is one way of eliminating the effects......Human experimental pain models are important tools in pain research. The primary aims of pain research in normal man is 1) to provide insight in pain mechanisms, 2) to provide a rational basis for clinical trials of pain relieving interventions, and 3) to confirm the anti-nociceptive effects...... demonstrated in animal models. Most often clinical pain is due to tissue damage leading to acute inflammation and hyperalgesia, but only few human pain models have examined pain responses in injured tissues. Therefore, models with controlled and reversible tissue trauma are needed. The human burn model...

  10. Bone hyperalgesia after mechanical impact stimulation: a human experimental pain model.

    Science.gov (United States)

    Finocchietti, Sara; Graven-Nielsen, Thomas; Arendt-Nielsen, Lars

    2014-12-01

    Hyperalgesia in different musculoskeletal structures including bones is a major clinical problem. An experimental bone hyperalgesia model was developed in the present study. Hyperalgesia was induced by three different weights impacted on the shinbone in 16 healthy male and female subjects. The mechanical impact pain threshold (IPT) was measured as the height from which three weights (165, 330, and 660 g) should be dropped to elicit pain at the shinbone. Temporal summation of pain to repeated impact stimuli was assessed. All these stimuli caused bone hyperalgesia. The pressure pain threshold (PPT) was assessed by a computerized pressure algometer using two different probes (1.0 and 0.5 cm(2)). All parameters were recorded before (0), 24, 72, and 96 h after the initial stimulations. The IPTs were lowest 24 h after hyperalgesia induction for all three weights and the effect lasted up to 72 h (p pain and hyperalgesia model may provide the basis for studying this fundamental mechanism of bone-related hyperalgesia and be used for profiling compounds developed for this target.

  11. Topical acetylsalicylic, salicylic acid and indomethacin suppress pain from experimental tissue acidosis in human skin.

    Science.gov (United States)

    Steen, K H; Reeh, P W; Kreysel, H W

    1995-09-01

    Topically applied acetylsalicylic acid (ASA), salicylic acid (SA) and indomethacin were tested in an experimental pain model that provides direct nociceptor excitation through cutaneous tissue acidosis. In 30 volunteers, sustained burning pain was produced in the palmar forearm through a continuous intradermal pressure infusion of a phosphate-buffered isotonic solution (pH 5.2). In 5 different, double-blind, randomized cross-over studies with 6 volunteers each, the flow rate of the syringe pump was individually adjusted to result in constant pain ratings of around 20% (50% in study 4) on a visual analog scale (VAS). The painful skin area was then covered with either placebo or the drugs which had been dissolved in diethylether. In the first study on 6 volunteers, ASA (60 mg/ml) or lactose (placebo) in diethylether (10 ml) was applied, using both arms at 3-day intervals. Both treatments resulted in sudden and profound pain relief due to the cooling effect of the evaporating ether. With lactose, however, the mean pain rating was restored close to the baseline within 6-8 min while, with ASA, it remained significantly depressed for the rest of the observation period (another 20 min). This deep analgesia was not accompanied by a loss of tactile sensation. The further studies served to show that indomethacin (4.5 mg/ml) and SA (60 mg/ml) were equally effective as ASA (each 92-96% pain reduction) and that the antinociceptive effects were due to local but not systemic actions, since ASA and SA dis not reach measurable plasma levels up to 3 h after topical applications. With a higher flow rate of acid buffer producing more intense pain (VAS 50%). ASA and SA were still able to significantly reduce the ratings by 90% or 84%, respectively. On the other hand, by increasing the flow rate by a factor of 2 on average, during the period of fully developed drug effect it was possible to overcome the pain suppression, which suggests a competitive mechanism of (acetyl-) salicylic

  12. Experimental pain in human temporal muscle induced by hypertonic saline, potassium and acidity

    DEFF Research Database (Denmark)

    Jensen, K; Norup, M

    1992-01-01

    chloride (n = 12) induced significantly more pain than isotonic saline (ANOVA, p less than 0.0001). Compared to control injections, hypertonic saline and potassium chloride induced a significant reduction in pressure-pain threshold (ANOVA, p less than 0.0001 and p less than 0.05). Forty-eight percent...

  13. Evaluation of anti-hyperalgesic and analgesic effects of two benzodiazepines in human experimental pain: a randomized placebo-controlled study.

    Directory of Open Access Journals (Sweden)

    Pascal H Vuilleumier

    Full Text Available Compounds that act on GABA-receptors produce anti-hyperalgesia in animal models, but little is known on their effects in humans. The aim of this study was to explore the potential usefulness of GABA-agonism for the control of pain in humans. Two agonists at the benzodiazepine-binding site of GABAA-receptors (clobazam and clonazepam were studied using multiple experimental pain tests. Positive results would support further investigation of GABA agonism for the control of clinical pain.In a randomized double-blind crossover design, 16 healthy male volunteers received clobazam 20 mg, clonazepam 1 mg and tolterodine 1 mg (active placebo. The area of static hyperalgesia after intradermal capsaicin injection was the primary endpoint. Secondary endpoints were: area of dynamic hyperalgesia, response to von Frey hair stimulation, pressure pain thresholds, conditioned pain modulation, cutaneous and intramuscular electrical pain thresholds (1, 5 and 20 repeated stimulation, and pain during cuff algometry.For the primary endpoint, an increase in the area of static hyperalgesia was observed after administration of placebo (p<0.001, but not after clobazam and clonazepam. Results suggestive for an anti-hyperalgesic effect of the benzodiazepines were obtained with all three intramuscular pain models and with cuff algometry. No effect could be detected with the other pain models employed.Collectively, the results are suggestive for a possible anti-hyperalgesic effect of drugs acting at the GABAA-receptors in humans, particularly in models of secondary hyperalgesia and deep pain. The findings are not conclusive, but support further clinical research on pain modulation by GABAergic drugs. Because of the partial results, future research should focus on compounds acting selectively on subunits of the GABA complex, which may allow the achievement of higher receptor occupancy than unselective drugs. Our data also provide information on the most suitable experimental

  14. Translational pain research: evaluating analgesic effect in experimental visceral pain models

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Andresen, Trine; Christrup, Lona Louring

    2009-01-01

    Deep visceral pain is frequent and presents major challenges in pain management, since its pathophysiology is still poorly understood. One way to optimize treatment of visceral pain is to improve knowledge of the mechanisms behind the pain and the mode of action of analgesic substances. This can ...... studies and clinical condition in patients suffering from visceral pain, and thus constitute the missing link in translational pain research.......Deep visceral pain is frequent and presents major challenges in pain management, since its pathophysiology is still poorly understood. One way to optimize treatment of visceral pain is to improve knowledge of the mechanisms behind the pain and the mode of action of analgesic substances. This can...... facilitate minimizing the gap between knowledge gained in animal and human clinical studies. Combining experimental pain studies and pharmacokinetic studies can improve understanding of the pharmacokinetic-pharmacodynamic relationship of analgesics and, thus, provide valuable insight into optimal clinical...

  15. The Effect of a Combination of Diclofenac and Methadone Applied as Gel in a Human Experimental Pain Model- A Randomized, Placebo-Controlled Trial

    DEFF Research Database (Denmark)

    Larsen, Isabelle M; Drewes, Asbjørn M; Olesen, Anne E

    2018-01-01

    should be low. We hypothesized that anti-allodynic and anti-hyperalgesic effects of Diclometh could be demonstrated in a human experimental pain model, and that Diclometh would be safe to administer. Thus, the aims were: 1) To compare two doses of Diclometh versus placebo; 2) To assess the safety profile...... of Diclometh. The study was a cross-over, randomized, double-blind, placebo-controlled comparison of two doses of Diclometh gel (0.1% and 0.2%) administered topically in healthy participants. Nerve growth factor (NGF) and capsaicin intradermal injections were used as human pain models. Pressure stimulation...... of anti-allodynic effect of Diclometh 0.2% was found. Additionally, it was demonstrated that Diclometh was safe to use. This article is protected by copyright. All rights reserved....

  16. Experimental knee pain reduces muscle strength

    DEFF Research Database (Denmark)

    Henriksen, Marius; Mortensen, Sara Rosager; Aaboe, Jens

    2011-01-01

    Pain is the principal symptom in knee pathologies and reduced muscle strength is a common observation among knee patients. However, the relationship between knee joint pain and muscle strength remains to be clarified. This study aimed at investigating the changes in knee muscle strength following...... experimental knee pain in healthy volunteers, and if these changes were associated with the pain intensities. In a crossover study, 18 healthy subjects were tested on 2 different days. Using an isokinetic dynamometer, maximal muscle strength in knee extension and flexion was measured at angular velocities 0....... Knee pain reduced the muscle strength by 5 to 15% compared to the control conditions (P knee extension and flexion at all angular velocities. The reduction in muscle strength was positively correlated to the pain intensity. Experimental knee pain significantly reduced knee extension...

  17. Experimental headache in humans

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg

    1995-01-01

    The need for valid human experimental models of headache is obvious. Several compounds have been proposed as headache-inducing agents, but only the nitroglycerin (NTG) model has been validated. In healthy subjects, intravenous infusions of the nitric oxide (NO) donor NTG induce a dose......-dependent headache and dilatation of the temporal, radial and middle cerebral artery. NTG-induced headache, although less intense, resembles migraine in pain characteristics, but the accompanying symptoms are rarely present. Cephalic large arteries are dilated during migraine headache as well as during NTG headache....... N-acetylcysteine enhances the formation of NO and potentiates NTG-induced headache, whereas mepyramine, a H1-antagonist capable of blocking histamine-induced headache, has no effect. Thus, the headache is dependent on NO or other steps in the NO cascade. The model is useful for pharmacological...

  18. Endogenous opioid antagonism in physiological experimental pain models

    DEFF Research Database (Denmark)

    Werner, Mads U; Pereira, Manuel P; Andersen, Lars Peter H

    2015-01-01

    hyperalgesia models (6 studies), 'pain' models (25 studies), summation models (2 studies), nociceptive reflex models (3 studies) and miscellaneous models (2 studies). A consistent reversal of analgesia by a MOR-antagonist was demonstrated in 10 of the 25 ITP-studies, including stress-induced analgesia and r...... ratings, threshold assessments and somatosensory evoked potentials (SSEP), did not appear consistent in 28 out of 32 'pain' model studies. In conclusion, only in 2 experimental human pain models, i.e., stress-induced analgesia and rTMS, administration of MOR-antagonist demonstrated a consistent effect......Opioid antagonists are pharmacological tools applied as an indirect measure to detect activation of the endogenous opioid system (EOS) in experimental pain models. The objective of this systematic review was to examine the effect of mu-opioid-receptor (MOR) antagonists in placebo-controlled, double...

  19. Motor responses to experimental Achilles tendon pain

    DEFF Research Database (Denmark)

    Henriksen, Marius; Aaboe, Jens; Graven-Nielsen, Thomas

    2011-01-01

    of the exercise are affected by Achilles tendon pain. Objective The authors aimed to determine the effects of experimental Achilles tendon pain on motor function during one-legged weight bearing ankle plantar and dorsal flexion exercises. Methods In a crossover study, with 16 healthy subjects tested on two......Background Achilles tendinopathies are characterised by pain and reduced function, and heavy-load exercises have been shown to be effective in the treatment of painful chronic Achilles tendinopathies. However, basic information is needed on how the biomechanics and neuromuscular control...... different days separated by 1 week, three-dimensional ground reaction forces, ankle joint kinematics and surface electromyography (EMG) of the lower leg muscles were recorded during one-legged full weight-bearing ankle plantar (concentric) and dorsal (eccentric) flexion exercises. Measurements were done...

  20. Association between Gene Polymorphisms and Pain Sensitivity Assessed in a Multi-Modal Multi-Tissue Human Experimental Model - An Explorative Study

    DEFF Research Database (Denmark)

    Nielsen, Lecia Møller; Olesen, Anne Estrup; Sato, Hiroe

    2016-01-01

    The genetic influence on sensitivity to noxious stimuli (pain sensitivity) remains controversial and needs further investigation. In the present study, the possible influence of polymorphisms in three opioid receptor (OPRM, OPRD and OPRK) genes and the catechol-O-methyltransferase (COMT) gene...... on pain sensitivity in healthy participants was investigated. Catechol-O-methyltransferase has an indirect effect on the mu opioid receptor by changing its activity through an altered endogenous ligand effect. Blood samples for genetic analysis were withdrawn in a multi-modal and multi-tissue experimental......, electrical and thermal visceral stimulations. A cold pressor test was also conducted. DNA was available from 38 of 40 participants. Compared to non-carriers of the COMT rs4680A allele, carriers reported higher bone pressure pain tolerance threshold (i.e. less pain) by up to 23.8% (p

  1. Nature and Nurture of Human Pain

    Directory of Open Access Journals (Sweden)

    Inna Belfer

    2013-01-01

    Full Text Available Humans are very different when it comes to pain. Some get painful piercings and tattoos; others can not stand even a flu shot. Interindividual variability is one of the main characteristics of human pain on every level including the processing of nociceptive impulses at the periphery, modification of pain signal in the central nervous system, perception of pain, and response to analgesic strategies. As for many other complex behaviors, the sources of this variability come from both nurture (environment and nature (genes. Here, I will discuss how these factors contribute to human pain separately and via interplay and how epigenetic mechanisms add to the complexity of their effects.

  2. IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP.

    Directory of Open Access Journals (Sweden)

    Stephen F Murphy

    Full Text Available Chronic pelvic pain syndrome (CPPS is the most common form of prostatitis, accounting for 90-95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17's role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS.

  3. IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP).

    Science.gov (United States)

    Murphy, Stephen F; Schaeffer, Anthony J; Done, Joseph; Wong, Larry; Bell-Cohn, Ashlee; Roman, Kenny; Cashy, John; Ohlhausen, Michelle; Thumbikat, Praveen

    2015-01-01

    Chronic pelvic pain syndrome (CPPS) is the most common form of prostatitis, accounting for 90-95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP) in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17's role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS.

  4. Effect of bidirectional rotation of an acupuncture needle at LI10 on acupuncture needle sensation and experimentally-induced contact heat pain in healthy human volunteers.

    Science.gov (United States)

    Benham, Alex; Johnson, Mark I

    2014-06-01

    There is insufficient evidence of a relationship between acupuncture needle sensations (de qi) and hypoalgesia. The aim of this study was to investigate the effects of bidirectional needle rotation at LI10 on acupuncture needle sensations and heat pain thresholds. Twenty-two healthy participants received one acupuncture needle at LI10 with bidirectional rotation of the needle in one experimental session and one acupuncture needle at LI10 with mock rotation in a separate session, in a randomised order. Measurements of heat pain thresholds were taken before needle insertion, during needle retention and 15 min after needle removal. At each measurement time point, participants rated needle sensations using the Massachusetts Acupuncture Sensation Scale (MASS) and a visual analogue scale (VAS) of overall intensity of needle sensation. Bidirectional needle rotation produced significantly higher scores for VAS, MASStotal, MASSpain and MASSsensation compared with mock rotation (all psensation and change in pain threshold after needling was only found when data from mock and rotation interventions were combined. Needle rotation increases the magnitude of hypoalgesia. There is tentative evidence that needle sensation may be associated with the amount of change in pain threshold. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. Pain management: a fundamental human right.

    Science.gov (United States)

    Brennan, Frank; Carr, Daniel B; Cousins, Michael

    2007-07-01

    This article surveys worldwide medical, ethical, and legal trends and initiatives related to the concept of pain management as a human right. This concept recently gained momentum with the 2004 European Federation of International Association for the Study of Pain (IASP) Chapters-, International Association for the Study of Pain- and World Health Organization-sponsored "Global Day Against Pain," where it was adopted as a central theme. We survey the scope of the problem of unrelieved pain in three areas, acute pain, chronic noncancer pain, and cancer pain, and outline the adverse physical and psychological effects and social and economic costs of untreated pain. Reasons for deficiencies in pain management include cultural, societal, religious, and political attitudes, including acceptance of torture. The biomedical model of disease, focused on pathophysiology rather than quality of life, reinforces entrenched attitudes that marginalize pain management as a priority. Strategies currently applied for improvement include framing pain management as an ethical issue; promoting pain management as a legal right, providing constitutional guarantees and statutory regulations that span negligence law, criminal law, and elder abuse; defining pain management as a fundamental human right, categorizing failure to provide pain management as professional misconduct, and issuing guidelines and standards of practice by professional bodies. The role of the World Health Organization is discussed, particularly with respect to opioid availability for pain management. We conclude that, because pain management is the subject of many initiatives within the disciplines of medicine, ethics and law, we are at an "inflection point" in which unreasonable failure to treat pain is viewed worldwide as poor medicine, unethical practice, and an abrogation of a fundamental human right.

  6. An investigation into the effects of frequency-modulated transcutaneous electrical nerve stimulation (TENS) on experimentally-induced pressure pain in healthy human participants.

    Science.gov (United States)

    Chen, Chih-Chung; Johnson, Mark I

    2009-10-01

    Frequency-modulated transcutaneous electrical nerve stimulation (TENS) delivers currents that fluctuate between preset boundaries over a fixed period of time. This study compared the effects of constant-frequency TENS and frequency-modulated TENS on blunt pressure pain in healthy human volunteers. Thirty-six participants received constant-frequency TENS (80 pps), frequency-modulated TENS (20 to 100 pps), and placebo (no current) TENS at a strong nonpainful intensity in a randomized cross-over manner. Pain threshold was taken from the forearm using pressure algometry. There were no statistical differences between constant-frequency TENS and frequency-modulated TENS after 20 minutes (OR = 1.54; CI, 0.29, 8.23, P = 1.0). Both constant-frequency TENS and frequency-modulated TENS were superior to placebo TENS (OR = 59.5, P TENS does not influence hypoalgesia to any greater extent than constant-frequency TENS when currents generate a strong nonpainful paraesthesia at the site of pain. The finding that frequency-modulated TENS and constant-frequency TENS were superior to placebo TENS provides further evidence that a strong yet nonpainful TENS intensity is a prerequisite for hypoalgesia. This study provides evidence that TENS, delivered at a strong nonpainful intensity, increases pain threshold to pressure algometry in healthy participants over and above that seen with placebo (no current) TENS. Frequency-modulated TENS does not increase hypoalgesia to any appreciable extent to that seen with constant-frequency TENS.

  7. Administrative Aspects of Human Experimentation.

    Science.gov (United States)

    Irvine, George W.

    1992-01-01

    The following administrative aspects of scientific experimentation with human subjects are discussed: the definition of human experimentation; the distinction between experimentation and treatment; investigator responsibility; documentation; the elements and principles of informed consent; and the administrator's role in establishing and…

  8. Bilateral experimental neck pain reorganize axioscapular muscle coordination and pain sensitivity.

    Science.gov (United States)

    Christensen, S W; Hirata, R P; Graven-Nielsen, T

    2017-04-01

    Neck pain is a large clinical problem where reorganized trunk and axioscapular muscle activities have been hypothesised contributing to pain persistence and pain hypersensitivity. This study investigated the effects of bilateral experimental neck pain on trunk and axioscapular muscle function and pain sensitivity. In 25 healthy volunteers, bilateral experimental neck pain was induced in the splenius capitis muscles by hypertonic saline injections. Isotonic saline was used as control. In sitting, subjects performed slow, fast and slow-resisted unilateral arm movements before, during and after injections. Electromyography (EMG) was recorded from eight shoulder and trunk muscles bilaterally. Pressure pain thresholds (PPTs) were assessed bilaterally at the neck, head and arm. Data were normalized to the before-measures. Compared with control and post measurements, experimental neck pain caused (1) decreased EMG activity of the ipsilateral upper trapezius muscles during all but slow-resisted down movements (p neck pain reorganized axioscapular and trunk muscle activity together with local hyperalgesia and widespread hypoalgesia indicating that acute neck pain immediately affects trunk and axioscapular function which may affect both assessment and treatment. Bilateral clinical neck pain alters axioscapular muscle coordination but only effects of unilateral experimental neck pain has been investigated. Bilateral experimental neck pain causes task-dependent reorganized axioscapular and trunk muscle activity in addition to widespread decrease in pressure pain sensitivity. © 2016 European Pain Federation - EFIC®.

  9. Patterns of experimentally induced pain in pericranial muscles

    DEFF Research Database (Denmark)

    Schmidt-Hansen, Peter Thede; Svensson, Peter; Jensen, Troels Staehelin

    2006-01-01

    into the masseter muscle (anova: P pain areas (anova: P cervically innervated muscles had significantly different patterns of spread and referral of pain according to trigeminally vs....... cervically innervated dermatomes (P pain patterns and pain sensitivity in different craniofacial muscles in healthy volunteers, which may be of importance for further research on different craniofacial pain conditions.......Nociceptive mechanisms in the craniofacial muscle tissue are poorly understood. The pain pattern in individual pericranial muscles has not been described before. Experimental muscle pain was induced by standardized infusions of 0.2 ml 1 m hypertonic saline into six craniofacial muscles (masseter...

  10. Time discounting and pain anticipation. Experimental evidence

    Directory of Open Access Journals (Sweden)

    Brañas Garza, Pablo

    2012-03-01

    Full Text Available This paper deals with pain anticipation experienced before medical procedures. our experimental results show that individuals with lower time discount factors are more prone to suffer pain in advance. We provide a framework to rationalize the connection between pain anticipation and impatience. in this set up, more impatient subjects, who only value very near events, mainly take into account the present negative effects of medical procedures (the costs, whereas more patient individuals have a net positive valuation of medical events, given that they are able to value both the cost incurred now and all the benefits to be accrued in the future.

    Este artículo trata de la anticipación del dolor experimentada antes de los procedimientos médicos. nuestros resultados experimentales muestran que los individuos con factor de descuento temporal más bajo son más proclives a sufrir dolor por adelantado. el artículo proporciona un marco en el que racionalizar la relación existente entre impaciencia y anticipación del dolor. en este marco, los sujetos más impacientes, que evalúan sólo los eventos muy próximos en el tiempo, focalizan su atención principalmente en los efectos negativos de los procedimientos médicos (sólo los costes, mientras que los individuos más pacientes tienen una valoración neta positiva de los actos médicos puesto que valoran tanto el coste en el que se incurre en el presente como los beneficios que se obtendrán en el futuro.

  11. Slow brushing reduces heat pain in humans.

    Science.gov (United States)

    Liljencrantz, J; Strigo, I; Ellingsen, D M; Krämer, H H; Lundblad, L C; Nagi, S S; Leknes, S; Olausson, H

    2017-08-01

    C-tactile (CT) afferents are unmyelinated low-threshold mechanoreceptors optimized for signalling affective, gentle touch. In three separate psychophysical experiments, we examined the contribution of CT afferents to pain modulation. In total, 44 healthy volunteers experienced heat pain and CT optimal (slow brushing) and CT sub-optimal (fast brushing or vibration) stimuli. Three different experimental paradigms were used: Concurrent application of heat pain and tactile (slow brushing or vibration) stimulation; Slow brushing, applied for variable duration and intervals, preceding heat pain; Slow versus fast brushing preceding heat pain. Slow brushing was effective in reducing pain, whereas fast brushing or vibration was not. The reduction in pain was significant not only when the CT optimal touch was applied simultaneously with the painful stimulus but also when the two stimuli were separated in time. For subsequent stimulation, the pain reduction was more pronounced for a shorter time interval between brushing and pain. Likewise, the effect was more robust when pain was preceded by a longer duration of brush stimulation. Strong CT-related pain reduction was associated with low anxiety and high calmness scores obtained by a state anxiety questionnaire. Slow brushing - optimal for CT activation - is effective in reducing pain from cutaneous heating. The precise mechanisms for the pain relief are as yet unknown but possible mechanisms include inhibition of nociceptive projection neurons at the level of the dorsal horn as well as analgesia through cortical mechanisms. Slow brushing stimuli - optimal for activation of C-tactile fibres - can reduce pain from cutaneous heating. No such effect was seen with fast brushing or vibration. These observations indicate the role of C-tactile fibres in pain modulation. © 2017 European Pain Federation - EFIC®.

  12. The influence of experimentally induced pain on shoulder muscle activity

    DEFF Research Database (Denmark)

    Diederichsen, L.P.; Winther, A.; Dyhre-Poulsen, P.

    2009-01-01

    healthy men (range 22-27 years), with no history of shoulder or cervical problems, were included in the study. Pain was induced by 5% hypertonic saline injections into the supraspinatus muscle or subacromially. Seated in a shoulder machine, subjects performed standardized concentric abduction (0A degrees......Muscle function is altered in painful shoulder conditions. However, the influence of shoulder pain on muscle coordination of the shoulder has not been fully clarified. The aim of the present study was to examine the effect of experimentally induced shoulder pain on shoulder muscle function. Eleven...... muscles. EMG was recorded before pain, during pain and after pain had subsided and pain intensity was continuously scored on a visual analog scale (VAS). During abduction, experimentally induced pain in the supraspinatus muscle caused a significant decrease in activity of the anterior deltoid, upper...

  13. Adaptations in the gait pattern with experimental hamstring pain

    DEFF Research Database (Denmark)

    Henriksen, M; Mortensen, Sara Rosager; Aaboe, J

    2011-01-01

    and little attention has been given to how pain in other muscles affects functional movement. The purpose of this study was to investigate the changes in the gait patterns of healthy subjects that occur during experimental muscle pain in the biceps femoris. In a cross-over study design, 14 healthy volunteers...... underwent EMG assisted 3D gait analyses before, during and after experimental biceps femoris pain induced by intramuscular injections of hypertonic saline. Isotonic saline injections were administered as a non-painful control. The experimental biceps femoris pain led to reductions in hip extensor moments......, knee flexor and lateral rotator moments. No changes in lower extremity kinematics and EMG activity in any of the recorded muscles were observed. It is concluded that experimental muscle pain in the biceps femoris leads to changes in the gait pattern in agreement with unloading of the painful muscle...

  14. Human milk for neonatal pain relief during ophthalmoscopy

    Directory of Open Access Journals (Sweden)

    Laiane Medeiros Ribeiro

    2013-10-01

    Full Text Available Ophthalmoscopy performed for the early diagnosis of retinopathy of prematurity (ROP is painful for preterm infants, thus necessitating interventions for minimizing pain. The present study aimed to establish the effectiveness of human milk, compared with sucrose, for pain relief in premature infants subjected to ophthalmoscopy for the early diagnosis of ROP. This investigation was a pilot, quasi-experimental study conducted with 14 premature infants admitted to the neonatal intensive care unit (NICU of a university hospital. Comparison between the groups did not yield a statistically significant difference relative to the crying time, salivary cortisol, or heart rate (HR. Human milk appears to be as effective as sucrose in relieving acute pain associated with ophthalmoscopy. The study’s limitations included its small sample size and lack of randomization. Experimental investigations with greater sample power should be performed to reinforce the evidence found in the present study.

  15. Experimental knee pain evoke spreading hyperalgesia and facilitated temporal summation of pain

    DEFF Research Database (Denmark)

    Jørgensen, Tanja Schjødt; Henriksen, Marius; Danneskiold-Samsøe, Bente

    2013-01-01

    OBJECTIVES: This study evaluated the deep-tissue pressure pain sensitivity and temporal summation of pain within and around healthy knees exposed to experimental pain. DESIGN: The study was designed as a randomized crossover trial, with each subject tested on 1 day. SETTING: All tests were carried...... occasions: baseline, immediately after the injection, and when pain had vanished. Assessments sites were located in the peripatellar region, vastus lateralis, and tibialis anterior muscles. RESULTS: The experimental knee pain model demonstrated 1) hyperalgesia to pressure stimulation on the infrapatellar...... fat pad during experimental pain, and 2) facilitated temporal summation of pressure pain at the infrapatellar fat pad and knee-related muscles. CONCLUSION: The increased sensitivity and temporal summation found in this study were exclusive to deep -tissue with no contralateral decreased pain...

  16. Effects of gabapentin on experimental somatic pain and temporal summation

    DEFF Research Database (Denmark)

    Arendt-Nielsen, Lars; Frøkjaer, Jens Brøndum; Staahl, Camilla

    2007-01-01

    at 2 Hz); (2) stimulus-response function relating pain intensity scores (visual analog scale, VAS) to increasing current intensities for electrical skin and muscle stimuli (single and repeated, determined at baseline); and (3) the pain intensity (VAS) and pain areas after intramuscular injection......, was to examine the effect of a single dose of 1200 mg gabapentin on multi-modal experimental cutaneous and muscle pain models. METHODS: The following pain models were applied: (1) pain thresholds to single and repeated cutaneous and intramuscular electrical stimulation (temporal summation to 5 stimuli delivered...... reduced the area under the pain intensity curve to hypertonic saline injections in the muscle (P = .02); and (3) significantly reduced the area of pain evoked by hypertonic saline (P = .03). CONCLUSIONS: Gabapentin reduces temporal summation of skin stimuli at pain threshold intensities; this may have...

  17. Prediction of postoperative pain: a systematic review of predictive experimental pain studies

    DEFF Research Database (Denmark)

    Werner, Mads Utke; Mjöbo, Helena N; Nielsen, Per R

    2010-01-01

    Quantitative testing of a patient's basal pain perception before surgery has the potential to be of clinical value if it can accurately predict the magnitude of pain and requirement of analgesics after surgery. This review includes 14 studies that have investigated the correlation between...... preoperative responses to experimental pain stimuli and clinical postoperative pain and demonstrates that the preoperative pain tests may predict 4-54% of the variance in postoperative pain experience depending on the stimulation methods and the test paradigm used. The predictive strength is much higher than...

  18. Manipulation of pain catastrophizing: An experimental study of healthy participants

    Directory of Open Access Journals (Sweden)

    Joel E Bialosky

    2008-11-01

    Full Text Available Joel E Bialosky1*, Adam T Hirsh2,3, Michael E Robinson2,3, Steven Z George1,3*1Department of Physical Therapy; 2Department of Clinical and Health Psychology; 3Center for Pain Research and Behavioral Health, University of Florida, Gainesville, Florida, USAAbstract: Pain catastrophizing is associated with the pain experience; however, causation has not been established. Studies which specifically manipulate catastrophizing are necessary to establish causation. The present study enrolled 100 healthy individuals. Participants were randomly assigned to repeat a positive, neutral, or one of three catastrophizing statements during a cold pressor task (CPT. Outcome measures of pain tolerance and pain intensity were recorded. No change was noted in catastrophizing immediately following the CPT (F(1,84 = 0.10, p = 0.75, partial η2 < 0.01 independent of group assignment (F(4,84 = 0.78, p = 0.54, partial η2 = 0.04. Pain tolerance (F(4 = 0.67, p = 0.62, partial η2 = 0.03 and pain intensity (F(4 = 0.73, p = 0.58, partial η2 = 0.03 did not differ by group. This study suggests catastrophizing may be difficult to manipulate through experimental pain procedures and repetition of specific catastrophizing statements was not sufficient to change levels of catastrophizing. Additionally, pain tolerance and pain intensity did not differ by group assignment. This study has implications for future studies attempting to experimentally manipulate pain catastrophizing.Keywords: pain, catastrophizing, experimental, cold pressor task, pain catastrophizing scale

  19. Effect of experimental chewing on masticatory muscle pain onset

    Directory of Open Access Journals (Sweden)

    Paulo César Rodrigues Conti

    2011-02-01

    Full Text Available OBJECTIVES: To evaluate the effect of a chewing exercise on pain intensity and pressure-pain threshold in patients with myofascial pain. METHODS: Twenty-nine consecutive women diagnosed with myofascial pain (MFP according to the Research Diagnostic Criteria comprised the experimental group and 15 healthy age-matched female were used as controls. Subjects were asked to chew a gum stick for 9 min and to stay at rest for another 9 min afterwards. Pain intensity was rated on a visual analog scale (VAS every 3 min. At 0, 9 and 18 min, the pressure-pain threshold (PPT was measured bilaterally on the masseter and the anterior, medium, and posterior temporalis muscles. RESULTS: Patients with myofascial pain reported increase (76% and no change (24% on the pain intensity measured with the VAS. A reduction of the PPT at all muscular sites after the exercise and a non-significant recovery after rest were also observed. CONCLUSION: The following conclusions can be drawn: 1. there are at least two subtypes of patients with myofascial pain that respond differently to experimental chewing; 2. the chewing protocol had an adequate discriminative ability in distinguishing patients with myofascial pain from healthy controls.

  20. Psychophysics, flare, and neurosecretory function in human pain models: capsaicin versus electrically evoked pain.

    Science.gov (United States)

    Geber, Christian; Fondel, Ricarda; Krämer, Heidrun H; Rolke, Roman; Treede, Rolfe-Detlef; Sommer, Claudia; Birklein, Frank

    2007-06-01

    Intradermal capsaicin injection (CAP) and electrical current stimulation (ES) are analyzed in respect to patterns and test-retest reliability of pain as well as sensory and neurosecretory changes. In 10 healthy subjects, 2x CAP (50 microg) and 2x ES (5 to 30 mA) were applied to the volar forearm. The time period between 2 identical stimulations was about 4 months. Pain ratings, areas of mechanical hyperalgesia, and allodynia were assessed. The intensity of sensory changes was quantified by using quantitative sensory testing. Neurogenic flare was assessed by using laser Doppler imaging. Calcitonin gene-related peptide (CGRP) release was quantified by dermal microdialysis in combination with an enzyme immunoassay. Time course and peak pain ratings were different between CAP and ES. Test-retest correlation was high (r > or = 0.73). Both models induced primary heat hyperalgesia and primary plus secondary pin-prick hyperalgesia. Allodynia occurred in about half of the subjects. Maximum flare sizes did not differ between CAP and ES, but flare intensities were higher for ES. Test-retest correlation was higher for flare sizes than for flare intensity. A significant CGRP release could only be measured after CAP. The different time courses of pain stimulation (CAP: rapidly decaying pain versus ES: pain plateau) led to different peripheral neurosecretory effects but induced similar central plasticity and hyperalgesia. The present study gives a detailed overview of psychophysical and neurosecretory characteristics induced by noxious stimulation with capsaicin and electrical current. We describe differences, similarities, and reproducibility of these human pain models. These data might help to interpret past and future results of human pain studies using experimental pain.

  1. Gender role affects experimental pain responses: a systematic review with meta-analysis.

    Science.gov (United States)

    Alabas, O A; Tashani, O A; Tabasam, G; Johnson, M I

    2012-10-01

    Gender role refers to the culturally and socially constructed meanings that describe how women and men should behave in certain situations according to feminine and masculine roles learned throughout life. The aim of this meta-analysis was to evaluate the relationship between gender role and experimental pain responses in healthy human participants. We searched computerized databases for studies published between January 1950 and May 2011 that had measured gender role in healthy human adults and pain response to noxious stimuli. Studies were entered into a meta-analysis if they calculated a correlation coefficient (r) for gender role and experimental pain. Searches yielded 4465 'hits' and 13 studies were eligible for review. Sample sizes were 67-235 participants and the proportion of female participants was 45-67%. Eight types of gender role instrument were used. Meta-analysis of six studies (406 men and 539 women) found a significant positive correlation between masculine and feminine personality traits and pain threshold and tolerance, with a small effect size (r = 0.17, p = 0.01). Meta-analysis of four studies (263 men and 297 women) found a significant negative correlation between gender stereotypes specific to pain and pain threshold and tolerance, with a moderate effect size (r = -0.41, p Gender stereotypes specific to pain scales showed stronger associations with sex differences in pain sensitivity response than masculine and feminine personality trait scales. © 2012 European Federation of International Association for the Study of Pain Chapters.

  2. Vicarious pain experiences while observing another in pain: an experimental approach

    Directory of Open Access Journals (Sweden)

    Sophie eVandenbroucke

    2013-06-01

    Full Text Available Objective: This study aimed at developing an experimental paradigm to assess vicarious pain experiences. We further explored the putative moderating role of observer’s characteristics such as hypervigilance for pain and dispositional empathy. Methods: Two experiments are reported using a similar procedure. Undergraduate students were selected based upon whether they reported vicarious pain in daily life, and categorized into a pain responder group or a comparison group. Participants were presented a series of videos showing hands being pricked whilst receiving occasionally pricking (electrocutaneous stimuli themselves. In congruent trials, pricking and visual stimuli were applied to the same spatial location. In incongruent trials, pricking and visual stimuli were in the opposite spatial location. Participants were required to report on which location they felt a pricking sensation. Of primary interest was the effect of viewing another in pain upon vicarious pain errors, i.e., the number of trials in which an illusionary sensation was reported. Furthermore, we explored the effect of individual differences in hypervigilance to pain, dispositional empathy and the rubber hand illusion (RHI upon vicarious pain errors. Results: Results of both experiments indicated that the number of vicarious pain errors was overall low. In line with expectations, the number of vicarious pain errors was higher in the pain responder group than in the comparison group. Self-reported hypervigilance for pain lowered the probability of reporting vicarious pain errors in the pain responder group, but dispositional empathy and the RHI did not. Conclusion: Our paradigm allows measuring vicarious pain experiences in students. However, the prevalence of vicarious experiences of pain is low, and only a small percentage of participants display the phenomenon. It remains however unknown which variables affect its occurrence.

  3. Experimental quadriceps muscle pain impairs knee joint control during walking

    DEFF Research Database (Denmark)

    Henriksen, Marius; Alkjaer, Tine; Lund, Hans

    2007-01-01

    Pain is a cardinal symptom in musculoskeletal diseases involving the knee joint, and aberrant movement patterns and motor control strategies are often present in these patients. However, the underlying neuromuscular mechanisms linking pain to movement and motor control are unclear. To investigate...... the functional significance of muscle pain on knee joint control during walking, three-dimensional gait analyses were performed before, during, and after experimentally induced muscle pain by means of intramuscular injections of hypertonic saline (5.8%) into vastus medialis (VM) muscle of 20 healthy subjects....... Isotonic saline (0.9%) was used as control. Surface electromyography (EMG) recordings of VM, vastus lateralis (VL), biceps femoris, and semitendinosus muscles were synchronized with the gait analyses. During experimental muscle pain, the loading response phase peak knee extensor moments were attenuated...

  4. The influence of working memory capacity on experimental heat pain.

    Science.gov (United States)

    Nakae, Aya; Endo, Kaori; Adachi, Tomonori; Ikeda, Takashi; Hagihira, Satoshi; Mashimo, Takashi; Osaka, Mariko

    2013-10-01

    Pain processing and attention have a bidirectional interaction that depends upon one's relative ability to use limited-capacity resources. However, correlations between the size of limited-capacity resources and pain have not been evaluated. Working memory capacity, which is a cognitive resource, can be measured using the reading span task (RST). In this study, we hypothesized that an individual's potential working memory capacity and subjective pain intensity are related. To test this hypothesis, we evaluated 31 healthy participants' potential working memory capacity using the RST, and then applied continuous experimental heat stimulation using the listening span test (LST), which is a modified version of the RST. Subjective pain intensities were significantly lower during the challenging parts of the RST. The pain intensity under conditions where memorizing tasks were performed was compared with that under the control condition, and it showed a correlation with potential working memory capacity. These results indicate that working memory capacity reflects the ability to process information, including precise evaluations of changes in pain perception. In this work, we present data suggesting that changes in subjective pain intensity are related, depending upon individual potential working memory capacities. Individual working memory capacity may be a phenotype that reflects sensitivity to changes in pain perception. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

  5. The influence of experimentally induced pain on shoulder muscle activity

    DEFF Research Database (Denmark)

    Diederichsen, L.P.; Winther, A.; Dyhre-Poulsen, P.

    2009-01-01

    muscles. EMG was recorded before pain, during pain and after pain had subsided and pain intensity was continuously scored on a visual analog scale (VAS). During abduction, experimentally induced pain in the supraspinatus muscle caused a significant decrease in activity of the anterior deltoid, upper......-105A degrees) at a speed of approximately 120A degrees/s, controlled by a metronome. During abduction, electromyographic (EMG) activity was recorded by intramuscular wire electrodes inserted in two deeply located shoulder muscles and by surface-electrodes over six superficially located shoulder...... trapezius and the infraspinatus and an increase in activity of lower trapezius and latissimus dorsi muscles. Following subacromial injection a significantly increased muscle activity was seen in the lower trapezius, the serratus anterior and the latissimus dorsi muscles. In conclusion, this study shows...

  6. Dissociable Learning Processes Underlie Human Pain Conditioning.

    Science.gov (United States)

    Zhang, Suyi; Mano, Hiroaki; Ganesh, Gowrishankar; Robbins, Trevor; Seymour, Ben

    2016-01-11

    Pavlovian conditioning underlies many aspects of pain behavior, including fear and threat detection [1], escape and avoidance learning [2], and endogenous analgesia [3]. Although a central role for the amygdala is well established [4], both human and animal studies implicate other brain regions in learning, notably ventral striatum and cerebellum [5]. It remains unclear whether these regions make different contributions to a single aversive learning process or represent independent learning mechanisms that interact to generate the expression of pain-related behavior. We designed a human parallel aversive conditioning paradigm in which different Pavlovian visual cues probabilistically predicted thermal pain primarily to either the left or right arm and studied the acquisition of conditioned Pavlovian responses using combined physiological recordings and fMRI. Using computational modeling based on reinforcement learning theory, we found that conditioning involves two distinct types of learning process. First, a non-specific "preparatory" system learns aversive facial expressions and autonomic responses such as skin conductance. The associated learning signals-the learned associability and prediction error-were correlated with fMRI brain responses in amygdala-striatal regions, corresponding to the classic aversive (fear) learning circuit. Second, a specific lateralized system learns "consummatory" limb-withdrawal responses, detectable with electromyography of the arm to which pain is predicted. Its related learned associability was correlated with responses in ipsilateral cerebellar cortex, suggesting a novel computational role for the cerebellum in pain. In conclusion, our results show that the overall phenotype of conditioned pain behavior depends on two dissociable reinforcement learning circuits. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. A dyadic analysis of siblings' relationship quality, behavioural responses, and pain experiences during experimental pain.

    Science.gov (United States)

    Schinkel, Meghan G; Chambers, Christine T; Corkum, Penny; Jacques, Sophie

    2018-04-16

    Research on family factors in paediatric pain has primarily focused on parents; the role of siblings has been largely ignored. This study examined whether sibling relationship quality was related to siblings' behaviours during experimental pain, and whether the behaviours of an observing sibling were related to children's pain outcomes. Ninety-two sibling dyads between 8-12 years old completed both observational and questionnaire measures of sibling relationship quality. Children took turns completing the cold pressor task (CPT) in a counterbalanced order with their sibling present. Pain outcomes (intensity, fear, tolerance) were recorded for each sibling, and the behaviour of the observing and participating siblings during the CPT were coded as attending, non-attending, and coping/encouragement. Structural equation modelling, using the actor-partner interdependence model, was conducted to analyse the dyadic data. While participating in the CPT with their sibling present, greater levels of warmth and positivity in the sibling relationship were related to children engaging in more non-attending behaviours and less attending behaviours. Greater levels of attending behaviours by the observing child was related to the sibling having a lower pain tolerance, and greater levels of coping/encouragement behaviours by the observing child was related to the sibling reporting greater pain intensity and fear during the CPT. Children with warmer/positive sibling relationships were more likely to respond to acute pain by shifting the focus away from their pain experience (e.g., through distraction) when a sibling was present. Pain-focused behaviours by an observing sibling are related to greater child pain and fear during experimental pain.

  8. Pain and executive functions: A unique relationship between Stroop task and experimentally induced pain

    NARCIS (Netherlands)

    Bjekic, J.; Zivanovic, M.; Puric, D.; Oosterman, J.M.; Filipovic, S.R.

    2018-01-01

    There is a growing body of evidence that a higher level of cognitive inhibition is associated with lower experimental pain sensitivity. However, a systematic examination of the association between executive functions, which include not only inhibition but also updating and shifting, and experimental

  9. The antinociceptive effect and adverse drug reactions of oxycodone in human experimental pain in relation to genetic variations in the OPRM1 and ABCB1 genes

    DEFF Research Database (Denmark)

    Zwisler, Stine T; Enggaard, Thomas P; Noehr-Jensen, Lene

    2010-01-01

    % for the wild-type carriers, P = 0.007). C3435T: The carriers of the variant T allele generally had less adverse drug reactions on oxycodone than the carriers of the wild-type genotype. G2677T/A: The carriers of the variant T allele had a better antinociceptive effect of oxycodone than the carriers of the wild......-type genotype in the cold pressor test (25% reduction vs. 15%, P = 0.015 in the discomfort rating and 25% reduction vs. 12%, P = 0.007 in the pain time AUC) and less adverse drug reactions. The combined wild-type genotype 3435CC-2677GG was associated with less antinociceptive effect of oxycodone...

  10. Ansiedade experimental humana Human experimental anxiety

    Directory of Open Access Journals (Sweden)

    Frederico Guilherme Graeff

    2007-01-01

    Full Text Available CONTEXTO: A ansiedade experimental no ser humano constitui-se em ponte entre os modelos animais e os ensaios clínicos. OBJETIVO: Este artigo focaliza métodos químicos e psicológicos utilizados para provocar ansiedade experimental em seres humanos. MÉTODOS: Realizou-se revisão seletiva da literatura. RESULTADOS: Os desafios farmacológicos têm sido usados principalmente para induzir ataques de pânico em pacientes com transtorno de pânico, os quais são mais sensíveis a eles que indivíduos normais ou pacientes portadores de outros transtornos psiquiátricos. Uma das mais importantes contribuições deste método é a de ter mostrado que os agentes panicogênicos mais seletivos, como o lactato ou a inalação de CO2, não ativam o eixo hormonal do estresse. Entre os métodos psicológicos, destacam-se o condicionamento de respostas elétricas da condutância da pele, cujo perfil farmacológico se aproxima daquele do transtorno de ansiedade generalizada, e o teste da simulação do falar em público, cuja farmacologia é semelhante à do transtorno de pânico. CONCLUSÕES: Tais resultados salientam a diferença entre a neurobiologia da ansiedade e a do pânico.BACKGROUND: Human experimental anxiety methods bridge the gap between animal models and clinical assays. OBJECTIVE: This article is focused on chemical and psychological procedures used to generate experimental anxiety in human beings. METHODS: A selective review of the literature has been carried out. RESULTS: Pharmacological challenges have been mainly used to induce panic attacks in panic disorder patients, who are more susceptible than normal individuals or patients with other psychiatric disorders. One of the most important contributions of this method is to have shown that the most selective panicogenic agents, such as lactate or CO2 inhalation, do not activate the hormonal stress axis. Among the psychological methods stand the conditioning of the electrical skin conductance

  11. Transcutaneous electrical nerve stimulation: nonparallel antinociceptive effects on chronic clinical pain and acute experimental pain.

    Science.gov (United States)

    Cheing, G L; Hui-Chan, C W

    1999-03-01

    To investigate to what extent a single 60-minute session of transcutaneous electrical nerve stimulation (TENS) would modify chronic clinical pain, acute experimental pain, and the flexion reflex evoked in chronic low back pain patients. Thirty young subjects with chronic low back pain were randomly allocated to two groups, receiving either TENS or placebo stimulation to the lumbosacral region for 60 minutes. The flexion reflex was elicited by an electrical stimulation applied to the subject's right sole and recorded electromyographically from the biceps femoris and the tibialis anterior muscles. Subjective sensation of low back pain and the electrically induced pain were measured by two separate visual analog scales, termed VAS(LBP) and VAS(FR), respectively. Data obtained before, during, and 60 minutes after TENS and placebo stimulations were analyzed using repeated measures ANOVA. The VAS(LBP) score was significantly reduced to 63.1% of the prestimulation value after TENS (pTENS protocol had different degrees of antinociceptive influence on chronic and acute pain in chronic low back pain patients.

  12. Nonpainful wide-area compression inhibits experimental pain.

    Science.gov (United States)

    Honigman, Liat; Bar-Bachar, Ofrit; Yarnitsky, David; Sprecher, Elliot; Granovsky, Yelena

    2016-09-01

    Compression therapy, a well-recognized treatment for lymphoedema and venous disorders, pressurizes limbs and generates massive non-noxious afferent sensory barrages. The aim of this study was to study whether such afferent activity has an analgesic effect when applied on the lower limbs, hypothesizing that larger compression areas will induce stronger analgesic effects, and whether this effect correlates with conditioned pain modulation (CPM). Thirty young healthy subjects received painful heat and pressure stimuli (47°C for 30 seconds, forearm; 300 kPa for 15 seconds, wrist) before and during 3 compression protocols of either SMALL (up to ankles), MEDIUM (up to knees), or LARGE (up to hips) compression areas. Conditioned pain modulation (heat pain conditioned by noxious cold water) was tested before and after each compression protocol. The LARGE protocol induced more analgesia for heat than the SMALL protocol (P < 0.001). The analgesic effect interacted with gender (P = 0.015). The LARGE protocol was more efficient for females, whereas the MEDIUM protocol was more efficient for males. Pressure pain was reduced by all protocols (P < 0.001) with no differences between protocols and no gender effect. Conditioned pain modulation was more efficient than the compression-induced analgesia. For the LARGE protocol, precompression CPM efficiency positively correlated with compression-induced analgesia. Large body area compression exerts an area-dependent analgesic effect on experimental pain stimuli. The observed correlation with pain inhibition in response to robust non-noxious sensory stimulation may suggest that compression therapy shares similar mechanisms with inhibitory pain modulation assessed through CPM.

  13. Analgesic effect of clobazam in chronic low-back pain but not in experimentally induced pain.

    Science.gov (United States)

    Schliessbach, J; Vuilleumier, P H; Siegenthaler, A; Bütikofer, L; Limacher, A; Juni, P; Zeilhofer, H U; Arendt-Nielsen, L; Curatolo, M

    2017-09-01

    Chronic pain is frequently associated with hypersensitivity of the nervous system, and drugs that increase central inhibition are therefore a potentially effective treatment. Benzodiazepines are potent modulators of GABAergic neurotransmission and are known to exert antihyperalgesic effects in rodents, but translation into patients are lacking. This study investigates the effect of the benzodiazepine clobazam in chronic low-back pain in humans. The aim of this study is to explore the effect of GABA modulation on chronic low-back pain and on quantitative sensory tests. In this double-blind cross-over study, 49 patients with chronic low-back pain received a single oral dose of clobazam 20 mg or active placebo tolterodine 1 mg. Pain intensity on the 0-10 numeric rating scale and quantitative sensory tests were assessed during 2 h after drug intake. Pain intensity in the supine position was significantly reduced by clobazam compared to active placebo (60 min: 2.9 vs. 3.5, p = 0.008; 90 min: 2.7 vs. 3.3, p = 0.024; 120 min: 2.4 vs. 3.1, p = 0.005). Pain intensity in the sitting position was not significantly different between groups. No effects on quantitative sensory tests were observed. This study suggests that clobazam has an analgesic effect in patients with chronic low-back pain. Muscle relaxation or sedation may have contributed to the effect. Development of substances devoid of these side effects would offer the potential to further investigate the antihyperalgesic action of GABAergic compounds. Modulation of GABAergic pain-inhibitory pathways may be a potential future therapeutic target. © 2017 European Pain Federation - EFIC®.

  14. Functional resonance magnetic imaging (fMRI) in adolescents with idiopathic musculoskeletal pain: a paradigm of experimental pain

    OpenAIRE

    Molina, Juliana; Amaro, Edson; da Rocha, Liana Guerra Sanches; Jorge, Liliana; Santos, Flavia Heloisa; Len, Claudio A.

    2017-01-01

    Background Studies on functional magnetic resonance imaging (fMRI) have shown that adults with musculoskeletal pain syndromes tolerate smaller amount of pressure (pain) as well as differences in brain activation patterns in areas related to pain.The objective of this study was to evaluate, through fMRI, the brain activation in adolescents with idiopathic musculoskeletal pain (IMP) while performing an experimental paradigm of pain. Methods The study included 10 consecutive adolescents with idi...

  15. Effects of ethnicity and gender role expectations of pain on experimental pain: a cross-cultural study.

    Science.gov (United States)

    Alabas, O A; Tashani, O A; Johnson, M I

    2013-05-01

    Gender role expectations of pain (GREP) have been shown to mediate sex differences in experimental pain. Few studies have investigated the role of ethnicity in shaping GREP. The aim of this study was to examine interactions between ethnicity and GREP on experimentally induced pressure and ischaemic pain in Libyan and white British students in their respective countries. Libyan (n = 124) and white British (n = 51) students completed a GREP questionnaire and their response to experimental pain was measured. Blunt pressure pain threshold (PPT) was measured over the 1st interosseous muscle using algometry. Pain intensity and pain unpleasantness (100 mm visual analogue scale) were measured at 1-min intervals during a submaximal effort tourniquet test on the forearm. Multivariate analysis of variance detected significant effects for Sex and Ethnicity on pain measurements. Men had higher PPTs than women (p 0.05). Libyan participants had higher pain intensity (p < 0.01) and pain unpleasantness (p < 0.05) ratings compared with white British participants. There were effects for Sex and Ethnicity for all GREP dimensions. Libyan participants exhibited stronger stereotypical views in GREP than white British participants (p < 0.001). GREP was the mediator of sex but not ethnic differences in pain report, suggesting that gender stereotypical attitudes to pain account for differences in pain expression between men and women. © 2012 European Federation of International Association for the Study of Pain Chapters.

  16. The genetic influence on the cortical processing of experimental pain and the moderating effect of pain status.

    Directory of Open Access Journals (Sweden)

    Helen Vossen

    Full Text Available BACKGROUND: Research suggests that the COMT Val(158Met, BDNF Val(66Met and OPRM1 A(118G polymorphisms moderate the experience of pain. In order to obtain experimental confirmation and extension of findings, cortical processing of experimentally-induced pain was used. METHOD: A sample of 78 individuals with chronic low back pain complaints and 37 healthy controls underwent EEG registration. Event-Related Potentials were measured in response to electrical nociceptive stimuli and moderation by COMT Val(158Met, BDNF Val(66Met and OPRM1 A(118G polymorphisms was assessed. RESULTS: Genetic variation did not have a direct effect on cortical processing of experimental pain. However, genetic effects (COMT Val(158Met and BDNF Val(66Met on experimental pain were moderated by the presence of chronic pain. In the presence of chronic pain, the COMT Met allele and the BDNF Met allele augmented cortical pain processing, whilst reducing pain processing in pain-free controls. No significant effects were found concerning the OPRM1 A(118G polymorphism. CONCLUSIONS: The current study suggests that chronic experience of pain enhances genetic sensitivity to experimentally induced mildly painful stimuli, possibly through a process of epigenetic modification.

  17. Striatal μ-opioid receptor availability predicts cold pressor pain threshold in healthy human subjects

    DEFF Research Database (Denmark)

    Hagelberg, Nora; Aalto, Sargo; Tuominen, Lauri

    2012-01-01

    the potential associations between μ-opioid receptor BP(ND) and psychophysical measures. The results show that striatal μ-opioid receptor BP(ND) predicts cold pressor pain threshold, but not cold pressor pain tolerance or tactile sensitivity. This finding suggests that striatal μ-opioid receptor density......Previous PET studies in healthy humans have shown that brain μ-opioid receptor activation during experimental pain is associated with reductions in the sensory and affective ratings of the individual pain experience. The aim of this study was to find out whether brain μ-opioid receptor binding...... at the resting state, in absence of painful stimulation, can be a long-term predictor of experimental pain sensitivity. We measured μ-opioid receptor binding potential (BP(ND)) with μ-opioid receptor selective radiotracer [(11)C]carfentanil and positron emission tomography (PET) in 12 healthy male subjects...

  18. The Modulation of Pain by Circadian and Sleep-Dependent Processes: A Review of the Experimental Evidence

    DEFF Research Database (Denmark)

    Hagenauer, Megan; Crodelle, Jennifer; Piltz, Sofia Helena

    2017-01-01

    conditions, pain sensitivity varies across the 24 h day, with highest sensitivity occurring during the evening in humans. Pain sensitivity is also modulated by sleep behavior, with pain sensitivity increasing in response to the build-up of homeostatic sleep pressure following sleep deprivation or sleep...... of physiologically meaningful stimulation levels. Following this normalization, we find that the estimated impact of the daily rhythm and of sleep deprivation on experimental pain measurements is surprisingly consistent across different pain modalities. We also review evidence documenting the impact of circadian...... rhythms and sleep deprivation on the neural circuitry in the spinal cord underlying pain sensation. The characterization of sleep-dependent and circadian influences on pain sensitivity in this review paper is used to develop and constrain the mathematical models introduced in the two companion articles....

  19. Historical development of epistemology and the study of pain: Place of neuromodulation of electroacupuncture in the experimental pain research

    Directory of Open Access Journals (Sweden)

    Bárbara B. Garrido-Suárez

    2013-10-01

    Full Text Available Despite the diffusion of acupuncture and its related techniques in Cuba and the World, its mechanism of action is still controversial, being considered by the most sceptics as placebo or some kind oriental myth, and it only should by related to this subjects as a matter of cultural-historical elements and not to science. The purpose of this revision is to characterize the pain sensation, after a critical analysis of the different philosophical streams related to the human knowledge and its expression in the historical evolution of the algology. On the other hand, to emphasize the importance of electroacupuncture-induced neuro-modulation in the field of experimental pain researches. In this content will be analyzed the concept of Khun paradigm and his ideas about the structure of scientific revolution in the theory of gates control and the explosion of pain researches in the last decades. It will related the introduction to acupuncture and its techniques in pain clinics, with scientific context of the historical moment. In addition, a space will be dedicated to the topic of complementary and alternative medicine on the century of evidence based medicine, given its scientific needs of validation in ours times.

  20. Viewing pictures of a romantic partner reduces experimental pain: involvement of neural reward systems.

    Science.gov (United States)

    Younger, Jarred; Aron, Arthur; Parke, Sara; Chatterjee, Neil; Mackey, Sean

    2010-10-13

    The early stages of a new romantic relationship are characterized by intense feelings of euphoria, well-being, and preoccupation with the romantic partner. Neuroimaging research has linked those feelings to activation of reward systems in the human brain. The results of those studies may be relevant to pain management in humans, as basic animal research has shown that pharmacologic activation of reward systems can substantially reduce pain. Indeed, viewing pictures of a romantic partner was recently demonstrated to reduce experimental thermal pain. We hypothesized that pain relief evoked by viewing pictures of a romantic partner would be associated with neural activations in reward-processing centers. In this functional magnetic resonance imaging (fMRI) study, we examined fifteen individuals in the first nine months of a new, romantic relationship. Participants completed three tasks under periods of moderate and high thermal pain: 1) viewing pictures of their romantic partner, 2) viewing pictures of an equally attractive and familiar acquaintance, and 3) a word-association distraction task previously demonstrated to reduce pain. The partner and distraction tasks both significantly reduced self-reported pain, although only the partner task was associated with activation of reward systems. Greater analgesia while viewing pictures of a romantic partner was associated with increased activity in several reward-processing regions, including the caudate head, nucleus accumbens, lateral orbitofrontal cortex, amygdala, and dorsolateral prefrontal cortex--regions not associated with distraction-induced analgesia. The results suggest that the activation of neural reward systems via non-pharmacologic means can reduce the experience of pain.

  1. Human parallels to experimental myopia?

    DEFF Research Database (Denmark)

    Fledelius, Hans C; Goldschmidt, Ernst; Haargaard, Birgitte

    2014-01-01

    acquiring new and basic knowledge, the practical object of the research is to reduce the burden of human myopia around the world. Acquisition and cost of optical correction is one issue, but associated morbidity counts more, with its global load of myopia-associated visual loss and blindness. The object......Raviola and Wiesel's monkey eyelid suture studies of the 1970s laid the cornerstone for the experimental myopia science undertaken since then. The aim has been to clarify the basic humoral and neuronal mechanisms behind induced myopization, its eye tissue transmitters in particular. Besides...... serve as inspiration to the laboratory research, which aims at solving the basic enigmas on a tissue level....

  2. Dose-specific effects of transcutaneous electrical nerve stimulation (TENS) on experimental pain: a systematic review.

    Science.gov (United States)

    Claydon, Leica S; Chesterton, Linda S; Barlas, Panos; Sim, Julius

    2011-09-01

    To determine the hypoalgesic effects of transcutaneous electrical nerve stimulation (TENS) parameter combinations on experimental models in healthy humans. Searches were performed using the electronic databases Ovid MEDLINE, CINAHL, AMED, and Web of Science (from inception to December 2009). Manual searches of journals and reference lists of retrieved trials were also performed. Randomized controlled trials (RCTs) were included in the review if they compared the hypoalgesic effect of TENS relative with placebo and control, using an experimental pain model in healthy human participants. Two reviewers independently selected the trials, assessed their methodologic quality and extracted data. Forty-three RCTs were eligible for inclusion. A best evidence synthesis revealed: Overall "conflicting" (inconsistent findings in multiple RCTs) evidence of TENS efficacy on experimental pain irrespective of TENS parameters used. Overall intense TENS has "moderate" evidence of efficacy (1 high-quality and 2 low-quality trials). Conventional TENS has overall conflicting evidence of efficacy, this is derived from "strong" evidence of efficacy (generally consistent findings in multiple high-quality RCTs) on pressure pain but strong evidence of inefficacy on other pain models. "Limited" evidence (positive findings from 1 RCT) of hypoalgesia exists for some novel parameters. Low-intensity, low-frequency, local TENS has strong evidence of inefficacy. Inappropriate TENS (using "barely perceptible" intensities) has moderate evidence of inefficacy. The level of hypoalgesic efficacy of TENS is clearly dependent on TENS parameter combination selection (defined in terms of intensity, frequency, and stimulation site) and experimental pain model. Future clinical RCTs may consider these TENS dose responses.

  3. The effect of electroacupuncture and tramadol on experimental tourniquet pain.

    Science.gov (United States)

    Musial, Frauke; Choi, Kyung-Eun; Gabriel, Tim; Lüdtke, Rainer; Rampp, Thomas; Michalsen, Andreas; Dobos, Gustav

    2012-03-01

    The hypoalgesic effect of electroacupuncture (EA) was directly compared with the analgesic effect of pharmacological interventions using the submaximum effort tourniquet technique (SETT). 125 healthy subjects (mean age 24.44±4.46 years; 62.4% female, 37.6% male) performed SETT at baseline and under one of five experimental conditions (n=25 per group): EA (2 Hz with burst pulses in alternating one-phase-square wave pulses; burst length 180 μs, burst frequency 80 Hz, stimulation time/pulse width 3 s), tramadol (50 mg), ibuprofen (400 mg), placebo pill or non-treatment control. EA was performed at LI4 and LI10 contralaterally with stimulation beginning 20 min before SETT and lasting throughout SETT. The pharmacological interventions were given in a double-blind design 1 h before the SETT assessment. Subjects showed a hypoalgesic effect of the opiate and of the EA for subjective pain rating (EA p=0.0051; tramadol p=0.0299), and pain tolerance index (time/rating) (EA p=0.043; tramadol p=0.047) analysed using analysis of covariance. More subjects reached the strict time limit of 30 min (analysed by logistic regression and adjusted OR as a post-hoc analysis) under EA compared with most other experimental conditions. Only EA and tramadol were not significantly different (95% Wald confidence limits: non-treatment control vs EA 0.011 to 0.542; placebo pill vs EA 0.009 to 0.438; ibuprofen vs EA 0.021 to 0.766; tramadol vs EA 0.065 to 1.436). In a laboratory setting, an EA procedure was as effective as a single dose of an orally administered opiate in reducing experimentally induced ischaemic pain.

  4. Masseter motor unit recruitment is altered in experimental jaw muscle pain

    NARCIS (Netherlands)

    Minami, I.; Akhter, R.; Albersen, I.; Burger, C.; Whittle, T.; Lobbezoo, F.; Peck, C.C.; Murray, G.M.

    2013-01-01

    Some management strategies for chronic orofacial pain are influenced by models (e.g., Vicious Cycle Theory, Pain Adaptation Model) proposing either excitation or inhibition within a painful muscle. The aim of this study was to determine if experimental painful stimulation of the masseter muscle

  5. Pain and Consciousness in Humans. Or Why Pain Subserves the Identity and Self-representation

    Directory of Open Access Journals (Sweden)

    Irene Venturella

    2016-08-01

    Full Text Available Traditional definitions of pain assume that an individual learns about pain through verbal usages related to the experience of injury in early life. This emphasis on the verbal correlates of pain restricts our understanding of pain to the context of adult human consciousness. In this paper we instead support the idea that our understanding of pain originates in neonatal experience and is not merely a verbally determined phenomenon. We also challenge the definition of pain as a merely sensory message related to peripheral tissue trauma. We aim to move beyond this definition by considering the relationship between the centre (Central Nervous System and periphery, taking into account certain phenomena such as phantom limbs and interoception. We show that pain helps an individual to develop a sense of awareness of himself immersed in a social context, and is thus a complex and adaptive phenomenon, that supports bodily integrity and social behavior.

  6. Pharmacology of human experimental anxiety

    Directory of Open Access Journals (Sweden)

    F.G. Graeff

    2003-04-01

    Full Text Available This review covers the effect of drugs affecting anxiety using four psychological procedures for inducing experimental anxiety applied to healthy volunteers and patients with anxiety disorders. The first is aversive conditioning of the skin conductance responses to tones. The second is simulated public speaking, which consists of speaking in front of a video camera, with anxiety being measured with psychometric scales. The third is the Stroop Color-Word test, in which words naming colors are painted in the same or in a different shade, the incongruence generating a cognitive conflict. The last test is a human version of a thoroughly studied animal model of anxiety, fear-potentiated startle, in which the eye-blink reflex to a loud noise is recorded. The evidence reviewed led to the conclusion that the aversive conditioning and potentiated startle tests are based on classical conditioning of anticipatory anxiety. Their sensitivity to benzodiazepine anxiolytics suggests that these models generate an emotional state related to generalized anxiety disorder. On the other hand, the increase in anxiety determined by simulated public speaking is resistant to benzodiazepines and sensitive to drugs affecting serotonergic neurotransmission. This pharmacological profile, together with epidemiological evidence indicating its widespread prevalence, suggests that the emotional state generated by public speaking represents a species-specific response that may be related to social phobia and panic disorder. Because of scant pharmacological data, the status of the Stroop Color-Word test remains uncertain. In spite of ethical and economic constraints, human experimental anxiety constitutes a valuable tool for the study of the pathophysiology of anxiety disorders.

  7. A practical guide and perspectives on the use of experimental pain modalities with children and adolescents

    Science.gov (United States)

    Birnie, Kathryn A; Caes, Line; Wilson, Anna C; Williams, Sara E; Chambers, Christine T

    2014-01-01

    SUMMARY Use of experimental pain is vital for addressing research questions that would otherwise be impossible to examine in the real world. Experimental induction of pain in children is highly scrutinized given the potential for harm and lack of direct benefit to a vulnerable population. However, its use has critically advanced our understanding of the mechanisms, assessment and treatment of pain in both healthy and chronically ill children. This article introduces various experimental pain modalities, including the cold pressor task, the water load symptom provocation test, thermal pain, pressure pain and conditioned pain modulation, and discusses their application for use with children and adolescents. It addresses practical implementation and ethical issues, as well as the advantages and disadvantages offered by each task. The incredible potential for future research is discussed given the array of experimental pain modalities now available to pediatric researchers. PMID:24641434

  8. Measuring empathy for human and robot hand pain using electroencephalography.

    Science.gov (United States)

    Suzuki, Yutaka; Galli, Lisa; Ikeda, Ayaka; Itakura, Shoji; Kitazaki, Michiteru

    2015-11-03

    This study provides the first physiological evidence of humans' ability to empathize with robot pain and highlights the difference in empathy for humans and robots. We performed electroencephalography in 15 healthy adults who observed either human- or robot-hand pictures in painful or non-painful situations such as a finger cut by a knife. We found that the descending phase of the P3 component was larger for the painful stimuli than the non-painful stimuli, regardless of whether the hand belonged to a human or robot. In contrast, the ascending phase of the P3 component at the frontal-central electrodes was increased by painful human stimuli but not painful robot stimuli, though the interaction of ANOVA was not significant, but marginal. These results suggest that we empathize with humanoid robots in late top-down processing similarly to human others. However, the beginning of the top-down process of empathy is weaker for robots than for humans.

  9. Experimental knee joint pain during strength training and muscle strength gain in healthy subjects

    DEFF Research Database (Denmark)

    Sørensen, T J; Langberg, Henning; Hodges, P W

    2012-01-01

    Knee joint pain and reduced quadriceps strength are cardinal symptoms in many knee pathologies. In people with painful knee pathologies, quadriceps exercise reduces pain, improves physical function, and increases muscle strength. A general assumption is that pain compromises muscle function...... and thus may prevent effective rehabilitation. This study evaluated the effects of experimental knee joint pain during quadriceps strength training on muscle strength gain in healthy individuals....

  10. Pain perception in people with Down syndrome: a synthesis of clinical and experimental research

    Science.gov (United States)

    McGuire, Brian E.; Defrin, Ruth

    2015-01-01

    People with an intellectual disability experience both acute and chronic pain with at least the same frequency as the general population. However, considerably less is known about the pain perception of people with Down syndrome. In this review paper, we evaluated the available clinical and experimental evidence. Some experimental studies of acute pain have indicated that pain threshold was higher than normal but only when using a reaction time method to measure pain sensitivity. However, when reaction time is not part of the calculation of the pain threshold, pain sensitivity in people with Down syndrome is in fact lower than normal (more sensitive to pain). Clinical studies of chronic pain have shown that people with an intellectual disability experience chronic pain and within that population, people with Down syndrome also experience chronic pain, but the precise prevalence of chronic pain in Down syndrome has yet to be established. Taken together, the literature suggests that people with Down syndrome experience pain, both acute and chronic, with at least the same frequency as the rest of the population. Furthermore, the evidence suggests that although acute pain expression appears to be delayed, once pain is registered, there appears to be a magnified pain response. We conclude by proposing an agenda for future research in this area. PMID:26283936

  11. Pain modulatory phenotypes differentiate subgroups with different clinical and experimental pain sensitivity

    DEFF Research Database (Denmark)

    Vaegter, Henrik B.; Graven-Nielsen, Thomas

    2016-01-01

    between subgroups. Cuff algometry was performed on lower legs in 400 chronic pain patients to assess pressure pain threshold (cPPT), pressure pain tolerance (cPTT), temporal summation of pain (TSP: increase in pain scores to ten repeated stimulations), and conditioned pain modulation (CPM: increase in c......PPT during cuff pain conditioning on the contralateral leg). Heat detection (HDT) and heat pain thresholds (HPT) at clinical painful and non-painful body areas were assessed. Based on TSP and CPM four distinct groups were formed: Group 1 (n=85) had impaired CPM and facilitated TSP. Group 2 (n=148) had...... impaired CPM and normal TSP. Group 3 (n=45) had normal CPM and facilitated TSP. Group 4 (n=122) had normal CPM and normal TSP. Group 1 showed more pain regions compared with the other three groups (PCPM and facilitated TSP plays an important role in widespread pain. Group 1...

  12. Acute pain induces insulin resistance in humans

    DEFF Research Database (Denmark)

    Greisen, J.; Juhl, C.B.; Grøfte, Thorbjørn

    2001-01-01

    Background: Painful trauma results in a disturbed metabolic state with impaired insulin sensitivity, which is related to the magnitude of the trauma. The authors explored whether pain per se influences hepatic and extrahepatic actions of insulin. Methods: Ten healthy male volunteers underwent two...... randomly sequenced hyperinsulinemic–euglycemic (insulin infusion rate, 0.6 mU · kg-1 · min-1 for 180 min) clamp studies 4 weeks apart. Self-controlled painful electrical stimulation was applied to the abdominal skin for 30 min, to a pain intensity of 8 on a visual analog scale of 0–10, just before...... the clamp procedure (study P). In the other study, no pain was inflicted (study C). Results: Pain reduced whole-body insulin-stimulated glucose uptake from 6.37 ± 1.87 mg · kg-1 · min-1 (mean ± SD) in study C to 4.97 ± 1.38 mg · kg-1 · min-1 in study P (P

  13. Role of synchronized oscillatory brain activity for human pain perception.

    Science.gov (United States)

    Hauck, Michael; Lorenz, Jürgen; Engel, Andreas K

    2008-01-01

    The understanding of cortical pain processing in humans has significantly improved since the development of modern neuroimaging techniques. Non-invasive electrophysiological approaches such as electro- and magnetoencephalography have proven to be helpful tools for the real-time investigation of neuronal signals and synchronous communication between cortical areas. In particular, time-frequency decomposition of signals recorded with these techniques seems to be a promising approach because different pain-related oscillatory changes can be observed within different frequency bands, which are likely to be linked to specific sensory and motor functions. In this review we discuss the latest evidence on pain-induced time-frequency signals and propose that changes in oscillatory activity reflect an essential communication mechanism in the brain that is modulated during pain processing. The importance of synchronization processes for normal and pathological pain processing, such as chronic pain states, is discussed.

  14. New perspectives in EEG/MEG brain mapping and PET/fMRI neuroimaging of human pain.

    Science.gov (United States)

    Chen, A C

    2001-10-01

    With the maturation of EEG/MEG brain mapping and PET/fMRI neuroimaging in the 1990s, greater understanding of pain processing in the brain now elucidates and may even challenge the classical theory of pain mechanisms. This review scans across the cultural diversity of pain expression and modulation in man. It outlines the difficulties in defining and studying human pain. It then focuses on methods of studying the brain in experimental and clinical pain, the cohesive results of brain mapping and neuroimaging of noxious perception, the implication of pain research in understanding human consciousness and the relevance to clinical care as well as to the basic science of human psychophysiology. Non-invasive brain studies in man start to unveil the age-old puzzles of pain-illusion, hypnosis and placebo in pain modulation. The neurophysiological and neurohemodynamic brain measures of experimental pain can now largely satisfy the psychophysiologist's dream, unimaginable only a few years ago, of modelling the body-brain, brain-mind, mind-matter duality in an inter-linking 3-P triad: physics (stimulus energy); physiology (brain activities); and psyche (perception). For neuropsychophysiology greater challenges lie ahead: (a) how to integrate a cohesive theory of human pain in the brain; (b) what levels of analyses are necessary and sufficient; (c) what constitutes the structural organisation of the pain matrix; (d) what are the modes of processing among and across the sites of these structures; and (e) how can neural computation of these processes in the brain be carried out? We may envision that modular identification and delineation of the arousal-attention, emotion-motivation and perception-cognition neural networks of pain processing in the brain will also lead to deeper understanding of the human mind. Two foreseeable impacts on clinical sciences and basic theories from brain mapping/neuroimaging are the plausible central origin in persistent pain and integration of

  15. Infusion pressure and pain during microneedle injection into skin of human subjects

    Science.gov (United States)

    Gupta, Jyoti; Park, Sohyun; Bondy, Brian; Felner, Eric I.; Prausnitz, Mark R.

    2011-01-01

    Infusion into skin using hollow microneedles offers an attractive alternative to hypodermic needle injections. However, the fluid mechanics and pain associated with injection into skin using a microneedle have not been studied in detail before. Here, we report on the effect of microneedle insertion depth into skin, partial needle retraction, fluid infusion flow rate and the co-administration of hyaluronidase on infusion pressure during microneedle-based saline infusion, as well as on associated pain in human subjects. Infusion of up to a few hundred microliters of fluid required pressures of a few hundred mmHg, caused little to no pain, and showed weak dependence on infusion parameters. Infusion of larger volumes up to 1 mL required pressures up to a few thousand mmHg, but still usually caused little pain. In general, injection of larger volumes of fluid required larger pressures and application of larger pressures cause more pain, although other experimental parameters also played a significant role. Among the intradermal microneedle groups, microneedle length had little effect; microneedle retraction lowered infusion pressure but increased pain; lower flow rate reduced infusion pressure and kept pain low; and use of hyaluronidase also lowered infusion pressure and kept pain low. We conclude that microneedles offer a simple method to infuse fluid into the skin that can be carried out with little to no pain. PMID:21684001

  16. Reliability of four experimental mechanical pain tests in children

    DEFF Research Database (Denmark)

    Søe, Ann-Britt Langager; Thomsen, Lise L; Tornoe, Birte

    2013-01-01

    In order to study pain in children, it is necessary to determine whether pain measurement tools used in adults are reliable measurements in children. The aim of this study was to explore the intrasession reliability of pressure pain thresholds (PPT) in healthy children. Furthermore, the aim was a...... was also to study the intersession reliability of the following four tests: (1) Total Tenderness Score; (2) PPT; (3) Visual Analog Scale score at suprapressure pain threshold; and (4) area under the curve (stimulus-response functions for pressure versus pain).......In order to study pain in children, it is necessary to determine whether pain measurement tools used in adults are reliable measurements in children. The aim of this study was to explore the intrasession reliability of pressure pain thresholds (PPT) in healthy children. Furthermore, the aim...

  17. Identifying experimental methods to determine the effect of pain on attention: a review of pain, caffeine, alcohol and nicotine studies.

    Science.gov (United States)

    Moore, David J; Keogh, Edmund; Eccleston, Christopher

    2009-12-01

    To review published studies of the effects that pain and common psychopharmacological substances have on the attentional performance of healthy adults. To identify which attentional tasks have the greatest potential to investigate the effect of pain on attention and provide recommendations for future research. A search was conducted for reports of experimental studies of attention in the context of pain. This was supplemented with studies on attention and caffeine, nicotine and alcohol. Studies were included if they used a healthy adult sample, used experimental or quasi-experimental methods, were relevant to the study of attention or interruption of pain and/or examined the acute effects of a substance on attention. Thirty-two papers, with 49 different experimental studies were identified (12 pain, 21 nicotine, 7 caffeine, 9 alcohol). Fourteen different tasks were reviewed across six domains of attention. The most promising measures of attention were the continuous performance task, flanker task, endogenous pre-cuing task, n-back task, inhibition task and dual task. There are reliable tasks that could be used to determine the effects of pain on attention. Future research is required that develops the utility of these tasks to improve our understanding of the effects pain and analgesia have on attentional performance. Copyright (c) 2009 John Wiley & Sons, Ltd.

  18. Reorganized trunk muscle activity during multidirectional floor perturbations after experimental low back pain

    DEFF Research Database (Denmark)

    Larsen, Lars Henrik; Hirata, Rogerio Pessoto; Graven-Nielsen, Thomas

    2016-01-01

    Low back pain changes the trunk muscle activity after external perturbations but the relationship between pain intensities and distributions and their effect on the trunk muscle activity remains unclear. The effects of unilateral and bilateral experimental low back pain on trunk muscle activity w...

  19. Multimodal distribution of human cold pain thresholds.

    Science.gov (United States)

    Lötsch, Jörn; Dimova, Violeta; Lieb, Isabel; Zimmermann, Michael; Oertel, Bruno G; Ultsch, Alfred

    2015-01-01

    It is assumed that different pain phenotypes are based on varying molecular pathomechanisms. Distinct ion channels seem to be associated with the perception of cold pain, in particular TRPM8 and TRPA1 have been highlighted previously. The present study analyzed the distribution of cold pain thresholds with focus at describing the multimodality based on the hypothesis that it reflects a contribution of distinct ion channels. Cold pain thresholds (CPT) were available from 329 healthy volunteers (aged 18 - 37 years; 159 men) enrolled in previous studies. The distribution of the pooled and log-transformed threshold data was described using a kernel density estimation (Pareto Density Estimation (PDE)) and subsequently, the log data was modeled as a mixture of Gaussian distributions using the expectation maximization (EM) algorithm to optimize the fit. CPTs were clearly multi-modally distributed. Fitting a Gaussian Mixture Model (GMM) to the log-transformed threshold data revealed that the best fit is obtained when applying a three-model distribution pattern. The modes of the identified three Gaussian distributions, retransformed from the log domain to the mean stimulation temperatures at which the subjects had indicated pain thresholds, were obtained at 23.7 °C, 13.2 °C and 1.5 °C for Gaussian #1, #2 and #3, respectively. The localization of the first and second Gaussians was interpreted as reflecting the contribution of two different cold sensors. From the calculated localization of the modes of the first two Gaussians, the hypothesis of an involvement of TRPM8, sensing temperatures from 25 - 24 °C, and TRPA1, sensing cold from 17 °C can be derived. In that case, subjects belonging to either Gaussian would possess a dominance of the one or the other receptor at the skin area where the cold stimuli had been applied. The findings therefore support a suitability of complex analytical approaches to detect mechanistically determined patterns from pain phenotype data.

  20. Sex differences in experimental measures of pain sensitivity and endogenous pain inhibition

    Directory of Open Access Journals (Sweden)

    Bulls HW

    2015-06-01

    Full Text Available Hailey W Bulls,1 Emily L Freeman,1 Austen JB Anderson,2 Meredith T Robbins,3 Timothy J Ness,3 Burel R Goodin1,3 1Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA; 2Department of Biology, Samford University, Birmingham, AL, USA; 3Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL, USA Abstract: It has been suggested that increased pain sensitivity and disruption of endogenous pain inhibitory processes may account, at least in part, for the greater prevalence and severity of chronic pain in women compared to men. However, previous studies addressing this topic have produced mixed findings. This study examined sex differences in pain sensitivity and inhibition using quantitative sensory testing (QST, while also considering the influence of other important factors such as depressive symptoms and sleep quality. Healthy men (n=24 and women (n=24 each completed a QST battery. This battery included an ischemic pain task (IPT that used a submaximal effort tourniquet procedure as well as a conditioned pain modulation (CPM procedure for the assessment of endogenous pain inhibition. Prior to QST, participants completed the Center for Epidemiologic Studies Depression Scale and the Pittsburgh Sleep Quality Index. Analyses revealed significant sex differences for the ischemic pain task and the conditioned pain modulation procedure, such that women tolerated the ischemic pain for a shorter amount of time and demonstrated less pain inhibition compared with men. This remained true even when accounting for sex differences in depressive symptoms and sleep quality. The results of this study suggest that women may be more pain sensitive and possess less-efficient endogenous pain inhibitory capacity compared with men. Whether interventions that decrease pain sensitivity and enhance pain inhibition in women ultimately improve their clinical pain outcomes is an area of research that deserves additional

  1. Movement does not promote recovery of motor output following acute experimental muscle pain

    DEFF Research Database (Denmark)

    Schabrun, Siobhan M.; Palsson, Thorvaldur Skuli; Thapa, Tribikram

    2018-01-01

    Objective.:  To examine the effect of motor activity on the magnitude and duration of altered corticomotor output following experimental muscle pain. Design. : Experimental, pre-post test. Setting. : University laboratory. Subjects. : Twenty healthy individuals. Methods.:  Participants were rando....... Understanding corticomotor depression in the postpain period and what factors promote recovery has relevance for clinical pain syndromes where ongoing motor dysfunction, in the absence of pain, may predispose to symptom persistence or recurrence....

  2. 5-HT modulation of pain perception in humans.

    Science.gov (United States)

    Martin, Sarah L; Power, Andrea; Boyle, Yvonne; Anderson, Ian M; Silverdale, Monty A; Jones, Anthony K P

    2017-10-01

    Although there is clear evidence for the serotonergic regulation of descending control of pain in animals, little direct evidence exists in humans. The majority of our knowledge comes from the use of serotonin (5-HT)-modulating antidepressants as analgesics in the clinical management of chronic pain. Here, we have used an acute tryptophan depletion (ATD) to manipulate 5-HT function and examine its effects of ATD on heat pain threshold and tolerance, attentional manipulation of nociceptive processing and mood in human volunteers. Fifteen healthy participants received both ATD and balanced amino acid (BAL) drinks on two separate sessions in a double-blind cross-over design. Pain threshold and tolerance were determined 4 h post-drink via a heat thermode. Additional attention, distraction and temperature discrimination paradigms were completed using a laser-induced heat pain stimulus. Mood was assessed prior and throughout each session. Our investigation reported that the ATD lowered plasma TRP levels by 65.05 ± 7.29% and significantly reduced pain threshold and tolerance in response to the heat thermode. There was a direct correlation between the reduction in total plasma TRP levels and reduction in thermode temperature. In contrast, ATD showed no effect on laser-induced pain nor significant impact of the distraction-induced analgesia on pain perception but did reduce performance of the painful temperature discrimination task. Importantly, all findings were independent of any effects of ATD on mood. As far as we are aware, it is the first demonstration of 5-HT effects on pain perception which are not confounded by mood changes.

  3. Human subjects and experimental irradiation

    International Nuclear Information System (INIS)

    Rosen, R.

    1985-01-01

    In recent years the public has expressed concern about the use of human subjects in scientific research. Some professional institutions have adopted codes of practice to guide them in this matter. At the University of New South Wales, where human subjects are used in teaching and research programmes, a committee ensures that high ethical standards are maintained. As the volunteer subjects do not gain any benefit themselves from the procedures, their level of risk is kept low. One type of procedure in which risk is becoming quantifiable, is the irradiation of human subjects. To assist peer review groups, the ICRP, WHO and the National Health and Medical Research Council have enunciated principles which should be followed in the irradiation of human volunteer subjects. In general the role of the Committee is advisory to protect the rights of the investigator, the subject, and the institution. Some of the inherent problems are discussed

  4. Modelling concentration-analgesia relationships for morphine to evaluate experimental pain models

    DEFF Research Database (Denmark)

    Sverrisdóttir, Eva; Foster, David John Richard; Upton, Richard Neil

    2015-01-01

    The aim of this study was to develop population pharmacokinetic-pharmacodynamic models for morphine in experimental pain induced by skin heat and muscle pressure, and to evaluate the experimental pain models with regard to assessment of morphine pharmacodynamics. In a randomized, double......-blind, placebo-controlled, crossover study, 39 healthy volunteers received an oral dose of 30 mg morphine hydrochloride or placebo. Non-linear mixed effects modelling was used to describe the plasma concentrations of morphine and metabolites, and the analgesic effect of morphine on experimental pain in skin...... and muscle. Baseline pain metrics varied between individuals and occasions, and were described with interindividual and interoccasion variability. Placebo-response did not change with time. For both pain metrics, morphine effect was proportional to baseline pain and was described with a linear model...

  5. The human pain genetics database: an interview with Luda Diatchenko.

    Science.gov (United States)

    Diatchenko, Luda

    2018-06-05

    Luda Diatchenko, MD, PhD is a Canada Excellence Research Chair in Human Pain Genetics, Professor, Faculty of Medicine, Department of Anesthesia and Faculty of Dentistry at McGill University, Alan Edwards Centre for Research on Pain. She earned her MD and PhD in the field of molecular biology from the Russian State Medical University. She started her career in industry, she was a Leader of the RNA Expression Group at Clontech, Inc., and subsequently, Director of Gene Discovery at Attagene, Inc. During this time, she was actively involved in the development of several widely used and widely cited molecular tools for the analysis of gene expression and regulation. Her academic career started at 2000 in the Center for Neurosensory Disorders at University of North Carolina. Her research since then is focused on determining the cellular and molecular biological mechanisms by which functional genetic variations impact human pain perception and risk of development of chronic pain conditions, enabling new approaches to identify new drug targets, treatment responses to analgesics and diagnostic. Multiple collaborative activities allow the Diatchenko group to take basic genetic findings all the way from human association studies, through molecular and cellular mechanisms to animal models and ultimately to human clinical trials. In total, she has authored or co-authored over 120 peer-reviewed research papers in journals, ten book chapters and edited a book in human pain genetics. She is a member and an active officer of several national and international scientific societies, including the International Association for the Study of Pain and the American Pain Society.

  6. Experimental knee pain impairs submaximal force steadiness in isometric, eccentric, and concentric muscle actions.

    Science.gov (United States)

    Rice, David A; McNair, Peter J; Lewis, Gwyn N; Mannion, Jamie

    2015-09-12

    Populations with knee joint damage, including arthritis, have noted impairments in the regulation of submaximal muscle force. It is difficult to determine the exact cause of such impairments given the joint pathology and associated neuromuscular adaptations. Experimental pain models that have been used to isolate the effects of pain on muscle force regulation have shown impaired force steadiness during acute pain. However, few studies have examined force regulation during dynamic contractions, and these findings have been inconsistent. The goal of the current study was to examine the effect of experimental knee joint pain on submaximal quadriceps force regulation during isometric and dynamic contractions. The study involved fifteen healthy participants. Participants were seated in an isokinetic dynamometer. Knee extensor force matching tasks were completed in isometric, eccentric, and concentric muscle contraction conditions. The target force was set to 10 % of maximum for each contraction type. Hypertonic saline was then injected into the infrapatella fat pad to generate acute joint pain. The force matching tasks were repeated during pain and once more 5 min after pain had subsided. Hypertonic saline resulted in knee pain with an average peak pain rating of 5.5 ± 2.1 (0-10 scale) that lasted for 18 ± 4 mins. Force steadiness significantly reduced during pain across all three muscle contraction conditions. There was a trend to increased force matching error during pain but this was not significant. Experimental knee pain leads to impaired quadriceps force steadiness during isometric, eccentric, and concentric contractions, providing further evidence that joint pain directly affects motor performance. Given the established relationship between submaximal muscle force steadiness and function, such an effect may be detrimental to the performance of tasks in daily life. In order to restore motor performance in people with painful arthritic conditions of the

  7. Periodontal CGRP contributes to orofacial pain following experimental tooth movement in rats.

    Science.gov (United States)

    Long, Hu; Liao, Lina; Gao, Meiya; Ma, Wenqiang; Zhou, Yang; Jian, Fan; Wang, Yan; Lai, Wenli

    2015-08-01

    Calcitonin-related gene peptide (CGRP) plays an important role in orofacial inflammatory pain. The aim of this study was to determine whether periodontal CGRP contributes to orofacial pain induced by experimental tooth movement in rats. Male Sprague-Dawley rats were used in this study. Closed coil springs were used to deliver forces. Rats were euthanized on 0d, 1d, 3d, 5d, 7d, and 14d following experimental tooth movement. Then, alveolar bones were obtained for immunostaining of periodontal tissues against CGRP. Two hours prior to euthanasia on each day, orofacial pain levels were assessed through rat grimace scale. CGRP and olcegepant (CGRP receptor antagonist) were injected into periodontal tissues to verify the roles of periodontal CGRP in orofacial pain induced by experimental tooth movement. Periodontal CGRP expression levels and orofacial pain levels were elevated on 1d, 3d, 5d, and 7d following experimental tooth movement. The two indices were significantly correlated with each other and fitted into a dose-response model. Periodontal administration of CGRP could elevate periodontal CGRP expressions and exacerbate orofacial pain. Moreover, olcegepant administration could decrease periodontal CGRP expressions and alleviate orofacial pain. Therefore, periodontal CGRP plays an important role in pain transmission and modulation following experimental tooth movement. We suggest that it may participate in a positive feedback aiming to amplify orofacial pain signals. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Induction and modulation of referred muscle pain in humans

    DEFF Research Database (Denmark)

    Laursen, René Johannes

    correlated to pain intensity, and LP and RP thresholds were reproducible within and between sessions. Experimentally (electrical stimulation and infusion of hypertonic saline) induced muscle pain seems to be mediated by myelinated and unmyelinated afferents and the peripheral component of RP by myelinated...... afferents. Furthermore, cutaneous anesthesia of the RP area resulted in a reduction of RP intensity of 22%, while a complete nerve block of afferents from the RP area resulted in a 40% reduction. In summary, observations from the presented experiments suggest that elicitation of referred muscle pain...... is depending on and correlated to local muscle pain. Peripheral input from the RP area is involved, but is not a necessary condition for RP to appear. The present studies as well as others suggest that central hyperexcitability is involved in the generation of RP, but further investigations on mechanisms of RP...

  9. Functional resonance magnetic imaging (fMRI) in adolescents with idiopathic musculoskeletal pain: a paradigm of experimental pain.

    Science.gov (United States)

    Molina, Juliana; Amaro, Edson; da Rocha, Liana Guerra Sanches; Jorge, Liliana; Santos, Flavia Heloisa; Len, Claudio A

    2017-11-14

    Studies on functional magnetic resonance imaging (fMRI) have shown that adults with musculoskeletal pain syndromes tolerate smaller amount of pressure (pain) as well as differences in brain activation patterns in areas related to pain.The objective of this study was to evaluate, through fMRI, the brain activation in adolescents with idiopathic musculoskeletal pain (IMP) while performing an experimental paradigm of pain. The study included 10 consecutive adolescents with idiopathic musculoskeletal pain (average age 16.3±1.0) and 10 healthy adolescents age-matched. fMRI exams were performed in a 3 T scanner (Magnetom Trio, Siemens) using an event-related design paradigm. Pressure stimuli were performed in the nondominant hand thumb, divided into two stages, fixed pain and variable pain. The two local Research Ethics Committees (Ethics Committee from Universidade Federal de São Paulo- Brazil, process number 0688/11, on July 1st, 2011 and Ethics Committee from Hospital Israelita Albert Einsten - Brazil, process number 1673, on October 19th, 2011) approved the study. The idiopathic musculoskeletal pain (IMP) group showed a reduced threshold for pain (3.7 kg/cm 2 versus 4.45 kg/cm 2 , p = 0.005). Control group presented increased bain activation when compared to IMP group in the following areas: thalamus (p = 0.00001), precentral gyrus (p = 0.0004) and middle frontal gyrus (p = 0.03). In intragroup analysis, IMP group showed greater brain activation during the unpredictable stimuli of the variable pain stage, especially in the lingual gyrus (p = 0.0001), frontal lobe (p = 0.0001), temporal gyrus (p = 0.0001) and precentral gyrus (p = 0.03), when compared to predictable stimulus of fixed pain. The same intragroup analysis with the control group showed greater activation during the unpredictable stimuli in regions of the precentral gyrus (p = 0.0001), subcallosal area (p = 0.0001), right and left occipital fusiform gyrus (p

  10. Effects of experimental muscle pain on muscle activity and co-ordination during static and dynamic motor function.

    Science.gov (United States)

    Graven-Nielsen, T; Svensson, P; Arendt-Nielsen, L

    1997-04-01

    The relation between muscle pain, muscle activity, and muscle co-ordination is still controversial. The present human study investigates the influence of experimental muscle pain on resting, static, and dynamic muscle activity. In the resting and static experiments, the electromyography (EMG) activity and the contraction force of m. tibialis anterior were assessed before and after injection of 0.5 ml hypertonic saline (5%) into the same muscle. In the dynamic experiment, injections of 0.5 ml hypertonic saline (5%) were performed into either m. tibialis anterior (TA) or m. gastrocnemius (GA) and the muscle activity and co-ordination were investigated during gait on a treadmill by EMG recordings from m. TA and m. GA. At rest no evidence of EMG hyperactivity was found during muscle pain. The maximal voluntary contraction (MVC) during muscle pain was significantly lower than the control condition (P Fibromyalgia and Myofascial Pain. Elsevier, Amsterdam, 1993, pp. 311-327.) which predicts increased activity of antagonistic muscle and decreased activity of agonistic muscle during experimental and clinical muscle pain.

  11. Are preoperative experimental pain assessments correlated with clinical pain outcomes after surgery?

    DEFF Research Database (Denmark)

    Sangesland, Anders; Støren, Carl; Vaegter, Henrik B.

    2017-01-01

    of surgery, QST variables, clinical pain outcome measure and main result. Results Most studies showed moderate to high risk of bias. Type of surgery investigated include 7 studies on total knee replacement, 5 studies on caesarean section, 4 studies on thoracic surgery, 2 studies on herniotomy, 2 studies......Background Pain after surgery is not uncommon with 30% of patients reporting moderate to severe postoperative pain. Early identification of patients prone to postoperative pain may be a step forward towards individualized pain medicine providing a basis for improved clinical management through......, and (3) the association between QST and pain after surgery was investigated. Forty-four unique studies were identified, with 30 studies on 2738 subjects meeting inclusion criteria. The methodological quality of the include studies was assessed and data extraction included study population, type...

  12. Human radiation experimentation: a health physics perspective

    International Nuclear Information System (INIS)

    Kathren, R.L.

    1996-01-01

    This paper observes ethical human experimentation can be considered in terms of two basic principles or tests: informed, willing and knowledgeable subjects; and expectation of benefits. A number of human experiments are evaluated in terms of these principles, including a sixteenth century toxicology experiment, the deliberate exposure by an x-ray pioneer, and the plutonium injection cases of the 1940's. The following rational ethic is proposed for the practice of health physics with respect to human radiation experimentation: At all levels, the health physicist has a professional as well as personal obligation to ensure that proper human requirements, including proper informed consent and willing subjects, arc carried out with respect to human radiation experimentation, and must be convinced that the real or potential benefits to be derived from the experiment clearly exceed the potential detriment and risk. (author)

  13. Reliability of four experimental mechanical pain tests in children

    Directory of Open Access Journals (Sweden)

    Soee AL

    2013-02-01

    Full Text Available Ann-Britt L Soee,1 Lise L Thomsen,2 Birte Tornoe,1,3 Liselotte Skov11Department of Pediatrics, Children’s Headache Clinic, Copenhagen University Hospital Herlev, Copenhagen, Denmark; 2Department of Neuropediatrics, Juliane Marie Centre, Copenhagen University Hospital Rigshospitalet, København Ø, Denmark; 3Department of Physiotherapy, Medical Department O, Copenhagen University Hospital Herlev, Herlev, DenmarkPurpose: In order to study pain in children, it is necessary to determine whether pain measurement tools used in adults are reliable measurements in children. The aim of this study was to explore the intrasession reliability of pressure pain thresholds (PPT in healthy children. Furthermore, the aim was also to study the intersession reliability of the following four tests: (1 Total Tenderness Score; (2 PPT; (3 Visual Analog Scale score at suprapressure pain threshold; and (4 area under the curve (stimulus–response functions for pressure versus pain.Participants and methods: Twenty-five healthy school children, 8–14 years of age, participated. Test 2, PPT, was repeated three times at 2 minute intervals on the same day to estimate PPT intrasession reliability using Cronbach’s alpha. Tests 1–4 were repeated after median 21 (interquartile range 10.5–22 days, and Pearson’s correlation coefficient was used to describe the intersession reliability.Results: The PPT test was precise and reliable (Cronbach’s alpha ≥ 0.92. All tests showed a good to excellent correlation between days (intersessions r = 0.66–0.81. There were no indications of significant systematic differences found in any of the four tests between days.Conclusion: All tests seemed to be reliable measurements in pain evaluation in healthy children aged 8–14 years. Given the small sample size, this conclusion needs to be confirmed in future studies.Keywords: repeatability, intraindividual reliability, pressure pain threshold, pain measurement, algometer

  14. Body awareness and responses to experimentally Induced pain

    Directory of Open Access Journals (Sweden)

    M. Minev

    2017-09-01

    Full Text Available PURPOSE. The aim of this study is to discuss personal and demographic factors that influence the relationship between physical activity and awareness of one's own body, as well as the pain response (threshold and tolerance of pain, situational anxiety and personality. In the study 38 healthy individual- volunteers, students in Trakia University - Stara Zagora were selected. All participants were divided into two groups: actively involved in individual or team sport (n = 19 and healthy normaly active subjects (non-athletes, n = 19. The age of the study participants ranged between 18 and 39 years, while the gender breakdown was as follows: men - 22 women – 16. Methods: Psychological Questionnaires: Body Awareness Questionnaire that asks subjects to rate, on a 4 point scale, the degree to which they were currently experiencing symptoms of sympathetic arousal, State Trait Anger Scale, and State Trait Anxiety Scale. Objective methods (cold pressure test are used only to determine the pain sensation and pain tolerance thresholds. The results of investigation support significant differences between athletes and non-athletes in pain thershold, body awareness and anxiety. The study conclusions discuss body awareness as an increasing factor for pain resistance in athletes and as an integral part of the learning process among them.

  15. Sex differences in pain: a brief review of clinical and experimental findings.

    Science.gov (United States)

    Bartley, E J; Fillingim, R B

    2013-07-01

    Recent years have witnessed substantially increased research regarding sex differences in pain. The expansive body of literature in this area clearly suggests that men and women differ in their responses to pain, with increased pain sensitivity and risk for clinical pain commonly being observed among women. Also, differences in responsivity to pharmacological and non-pharmacological pain interventions have been observed; however, these effects are not always consistent and appear dependent on treatment type and characteristics of both the pain and the provider. Although the specific aetiological basis underlying these sex differences is unknown, it seems inevitable that multiple biological and psychosocial processes are contributing factors. For instance, emerging evidence suggests that genotype and endogenous opioid functioning play a causal role in these disparities, and considerable literature implicates sex hormones as factors influencing pain sensitivity. However, the specific modulatory effect of sex hormones on pain among men and women requires further exploration. Psychosocial processes such as pain coping and early-life exposure to stress may also explain sex differences in pain, in addition to stereotypical gender roles that may contribute to differences in pain expression. Therefore, this review will provide a brief overview of the extant literature examining sex-related differences in clinical and experimental pain, and highlights several biopsychosocial mechanisms implicated in these male-female differences. The future directions of this field of research are discussed with an emphasis aimed towards further elucidation of mechanisms which may inform future efforts to develop sex-specific treatments.

  16. Gait changes in patients with knee osteoarthritis are replicated by experimental knee pain

    DEFF Research Database (Denmark)

    Henriksen, Marius; Nielsen, Thomas Graven; Aaboe, Jens

    2010-01-01

    Medial knee osteoarthritis (OA) is characterized by pain and associated with abnormal knee moments during walking. The relationship between knee OA pain and gait changes remains to be clarified, and a better understanding of this link could advance the treatment and prevention of disease...... progression. This study investigated changes in knee moments during walking following experimental knee pain in healthy volunteers, and whether these changes replicated the joint moments observed in medial knee OA patients....

  17. Objective Markers of the analgesic response to morphine in experimental pain research

    DEFF Research Database (Denmark)

    Brokjær, Anne; Olesen, Anne Estrup; Kreilgaard, Mads

    2015-01-01

    INTRODUCTION: In experimental pain research the effect of opioids is normally assessed by verbal subjective response to analgesia. However, as many confounders in pain assessment exist, objective bed-side assessment of the effect is highly warranted. Therefore, we aimed to assess the effect...

  18. Psychological Factors Predict Local and Referred Experimental Muscle Pain: A Cluster Analysis in Healthy Adults

    Science.gov (United States)

    Lee, Jennifer E.; Watson, David; Frey-Law, Laura A.

    2012-01-01

    Background Recent studies suggest an underlying three- or four-factor structure explains the conceptual overlap and distinctiveness of several negative emotionality and pain-related constructs. However, the validity of these latent factors for predicting pain has not been examined. Methods A cohort of 189 (99F; 90M) healthy volunteers completed eight self-report negative emotionality and pain-related measures (Eysenck Personality Questionnaire-Revised; Positive and Negative Affect Schedule; State-Trait Anxiety Inventory; Pain Catastrophizing Scale; Fear of Pain Questionnaire; Somatosensory Amplification Scale; Anxiety Sensitivity Index; Whiteley Index). Using principal axis factoring, three primary latent factors were extracted: General Distress; Catastrophic Thinking; and Pain-Related Fear. Using these factors, individuals clustered into three subgroups of high, moderate, and low negative emotionality responses. Experimental pain was induced via intramuscular acidic infusion into the anterior tibialis muscle, producing local (infusion site) and/or referred (anterior ankle) pain and hyperalgesia. Results Pain outcomes differed between clusters (multivariate analysis of variance and multinomial regression), with individuals in the highest negative emotionality cluster reporting the greatest local pain (p = 0.05), mechanical hyperalgesia (pressure pain thresholds; p = 0.009) and greater odds (2.21 OR) of experiencing referred pain compared to the lowest negative emotionality cluster. Conclusion Our results provide support for three latent psychological factors explaining the majority of the variance between several pain-related psychological measures, and that individuals in the high negative emotionality subgroup are at increased risk for (1) acute local muscle pain; (2) local hyperalgesia; and (3) referred pain using a standardized nociceptive input. PMID:23165778

  19. Masseter motor unit recruitment is altered in experimental jaw muscle pain.

    Science.gov (United States)

    Minami, I; Akhter, R; Albersen, I; Burger, C; Whittle, T; Lobbezoo, F; Peck, C C; Murray, G M

    2013-02-01

    Some management strategies for chronic orofacial pain are influenced by models (e.g., Vicious Cycle Theory, Pain Adaptation Model) proposing either excitation or inhibition within a painful muscle. The aim of this study was to determine if experimental painful stimulation of the masseter muscle resulted in only increases or only decreases in masseter activity. Recordings of single-motor-unit (SMU, basic functional unit of muscle) activity were made from the right masseters of 10 asymptomatic participants during biting trials at the same force level and direction under infusion into the masseter of isotonic saline (no-pain condition), and in another block of biting trials on the same day, with 5% hypertonic saline (pain condition). Of the 36 SMUs studied, 2 SMUs exhibited a significant (p units were present only during the no-pain block and 10 units during the pain block only. The findings suggest that, rather than only excitation or only inhibition within a painful muscle, a re-organization of activity occurs, with increases and decreases occurring within the painful muscle. This suggests the need to re-assess management strategies based on models that propose uniform effects of pain on motor activity.

  20. Neurochemical dynamics of acute orofacial pain in the human trigeminal brainstem nuclear complex.

    Science.gov (United States)

    de Matos, Nuno M P; Hock, Andreas; Wyss, Michael; Ettlin, Dominik A; Brügger, Mike

    2017-11-15

    The trigeminal brainstem sensory nuclear complex is the first central relay structure mediating orofacial somatosensory and nociceptive perception. Animal studies suggest a substantial involvement of neurochemical alterations at such basal CNS levels in acute and chronic pain processing. Translating this animal based knowledge to humans is challenging. Human related examining of brainstem functions are challenged by MR related peculiarities as well as applicability aspects of experimentally standardized paradigms. Based on our experience with an MR compatible human orofacial pain model, the aims of the present study were twofold: 1) from a technical perspective, the evaluation of proton magnetic resonance spectroscopy at 3 T regarding measurement accuracy of neurochemical profiles in this small brainstem nuclear complex and 2) the examination of possible neurochemical alterations induced by an experimental orofacial pain model. Data from 13 healthy volunteers aged 19-46 years were analyzed and revealed high quality spectra with significant reductions in total N-acetylaspartate (N-acetylaspartate + N-acetylaspartylglutamate) (-3.7%, p = 0.009) and GABA (-10.88%, p = 0.041) during the pain condition. These results might reflect contributions of N-acetylaspartate and N-acetylaspartylglutamate in neuronal activity-dependent physiologic processes and/or excitatory neurotransmission, whereas changes in GABA might indicate towards a reduction in tonic GABAergic functioning during nociceptive signaling. Summarized, the present study indicates the applicability of 1 H-MRS to obtain neurochemical dynamics within the human trigeminal brainstem sensory nuclear complex. Further developments are needed to pave the way towards bridging important animal based knowledge with human research to understand the neurochemistry of orofacial nociception and pain. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Antinociceptive Interaction of Tramadol with Gabapentin in Experimental Mononeuropathic Pain.

    Science.gov (United States)

    Miranda, Hugo F; Noriega, Viviana; Prieto, Juan Carlos; Zanetta, Pilar; Castillo, Rodrigo; Aranda, Nicolás; Sierralta, Fernando

    2016-08-01

    Neuropathic pain is the result of injury to the nervous system, and different animal models have been established to meet the manifestations of neuropathy. The pharmacotherapy for neuropathic pain includes gabapentin and tramadol, but these are only partially effective when given alone. The aim of this study was to assess the antinociceptive interaction between both drugs using the isobolographic analysis and changes of the IL-1β concentration in a mouse model of neuropathic pain (partial sciatic nerve ligation or PSNL). The i.p. administration of gabapentin (5-100 mg/kg) or tramadol (12.5-100 mg/kg) displayed a dose-dependent antinociception in the hot plate assay of PSNL mice, and effects induced by gabapentin with tramadol were synergistic. Administration of gabapentin or tramadol reversed significantly the increase in the concentration of IL-1β induced by PSNL after either 7 or 14 days and their combination was significantly more potent in reversing the elevated concentration of IL-1β. The synergism obtained by the co-administration of gabapentin and tramadol is proposed to result from action on different mechanisms in pain pathways. Gabapentin or tramadol or their combination modulates the expression of pro-inflammatory cytokine, IL-1β, in a model of mice PSNL which could be due to an inhibition of glial function. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  2. Side effects of pain and analgesia in animal experimentation.

    Science.gov (United States)

    Jirkof, Paulin

    2017-03-22

    This review highlights selected effects of untreated pain and of widely used analgesics such as opioids, non-steroid anti-inflammatory drugs and antipyretics, to illustrate the relevance of carefully planned, appropriate and controlled analgesia for greater reproducibility in animal experiments involving laboratory rodents.

  3. The effects of experimental pain and induced optimism on working memory task performance.

    Science.gov (United States)

    Boselie, Jantine J L M; Vancleef, Linda M G; Peters, Madelon L

    2016-07-01

    Pain can interrupt and deteriorate executive task performance. We have previously shown that experimentally induced optimism can diminish the deteriorating effect of cold pressor pain on a subsequent working memory task (i.e., operation span task). In two successive experiments we sought further evidence for the protective role of optimism on pain-induced working memory impairments. We used another working memory task (i.e., 2-back task) that was performed either after or during pain induction. Study 1 employed a 2 (optimism vs. no-optimism)×2 (pain vs. no-pain)×2 (pre-score vs. post-score) mixed factorial design. In half of the participants optimism was induced by the Best Possible Self (BPS) manipulation, which required them to write and visualize about a life in the future where everything turned out for the best. In the control condition, participants wrote and visualized a typical day in their life (TD). Next, participants completed either the cold pressor task (CPT) or a warm water control task (WWCT). Before (baseline) and after the CPT or WWCT participants working memory performance was measured with the 2-back task. The 2-back task measures the ability to monitor and update working memory representation by asking participants to indicate whether the current stimulus corresponds to the stimulus that was presented 2 stimuli ago. Study 2 had a 2 (optimism vs. no-optimism)×2 (pain vs. no-pain) mixed factorial design. After receiving the BPS or control manipulation, participants completed the 2-back task twice: once with painful heat stimulation, and once without any stimulation (counter-balanced order). Continuous heat stimulation was used with temperatures oscillating around 1°C above and 1°C below the individual pain threshold. In study 1, the results did not show an effect of cold pressor pain on subsequent 2-back task performance. Results of study 2 indicated that heat pain impaired concurrent 2-back task performance. However, no evidence was found

  4. Placebo effect of an inert gel on experimentally induced leg muscle pain

    Directory of Open Access Journals (Sweden)

    James G Hopker

    2010-11-01

    Full Text Available James G Hopker1, Abigail J Foad2, Christopher J Beedie2, Damian A Coleman2, Geoffrey Leach11Centre for Sports Studies, University of Kent, Chatham, Kent, UK; 2Department of Sports Science, Tourism and Leisure, Canterbury Christ Church University, Canterbury, Kent, UKPurpose: This study examined the therapeutic effects of an inert placebo gel on experimentally induced muscle pain in a sports therapy setting. It aimed to investigate the degree to which conditioned analgesia, coupled with an expectation of intervention, was a factor in subsequent analgesia.Methods: Participants were sixteen male and eight female sports therapy students at a UK University. With institutional ethics board approval and following informed consent procedures, each was exposed to pain stimulus in the lower leg in five conditions, ie, conditioning, prebaseline, experimental (two placebo gel applications, and postbaseline. In conditioning trials, participants identified a level of pain stimulus equivalent to a perceived pain rating of 6/10. An inert placebo gel was then applied to the site with the explicit instruction that it was an analgesic. Participants were re-exposed to the pain stimulus, the level of which, without their knowledge, had been decreased, creating the impression of an analgesic effect resulting from the gel. In experimental conditions, the placebo gel was applied and the level of pain stimulus required to elicit a pain rating of 6/10 recorded.Results: Following application of the placebo gel, the level of pain stimulus required to elicit a pain rating of 6/10 increased by 8.2%. Application of the placebo gel significantly decreased participant’s perceptions of muscle pain (P = 0.001.Conclusion: Subjects’ experience and expectation of pain reduction may be major factors in the therapeutic process. These factors should be considered in the sports therapeutic environment.Keywords: conditioning, expectation, perception, positive belief, sports therapy

  5. Effect of ambient temperature on human pain and temperature perception.

    Science.gov (United States)

    Strigo, I A; Carli, F; Bushnell, M C

    2000-03-01

    Animal studies show reduced nociceptive responses to noxious heat stimuli and increases in endogenous beta-endorphin levels in cold environments, suggesting that human pain perception may be dependent on ambient temperature. However, studies of changes in local skin temperature on human pain perception have yielded variable results. This study examines the effect of both warm and cool ambient temperature on the perception of noxious and innocuous mechanical and thermal stimuli. Ten subjects (7 men and 3 women, aged 20-23 yr) used visual analog scales to rate the stimulus intensity, pain intensity, and unpleasantness of thermal (0-50 degrees C) and mechanical (1.2-28.9 g) stimuli applied on the volar forearm with a 1-cm2 contact thermode and von Frey filaments, respectively. Mean skin temperatures were measured throughout the experiment by infrared pyrometer. Each subject was tested in ambient temperatures of 15 degrees C (cool), 25 degrees C (neutral), and 35 degrees C (warm) on separate days, after a 30-min acclimation to the environment. Studies began in the morning after an 8-h fast. Mean skin temperature was altered by ambient temperature (cool room: 30.1 degrees C; neutral room: 33.4 degrees C; warm room: 34.5 degrees C; P cool than in the neutral environment (P cool room and that noxious heat stimuli were more unpleasant in a warm environment. Environmental temperature did not alter ratings of warm (37 and 40 degrees C) or mechanical stimuli. These results indicate that, in humans, a decrease in skin temperature following exposure to cool environments reduces thermal pain. Suppression of Adelta primary afferent cold fiber activity has been shown to increase cold pain produced by skin cooling. Our current findings may represent the reverse phenomenon, i.e., a reduction in thermal nociceptive transmission by the activation of Adelta cutaneous cold fibers.

  6. The role of periodontal ASIC3 in orofacial pain induced by experimental tooth movement in rats.

    Science.gov (United States)

    Gao, Meiya; Long, Hu; Ma, Wenqiang; Liao, Lina; Yang, Xin; Zhou, Yang; Shan, Di; Huang, Renhuan; Jian, Fan; Wang, Yan; Lai, Wenli

    2016-12-01

    This study aimed to clarify the roles of Acid-sensing ion channel 3 (ASIC3) in orofacial pain following experimental tooth movement. Sixty male Sprague-Dawley rats were divided into the experimental group (40g, n = 30) and the sham group (0g, n = 30). Closed coil springs were ligated between maxillary incisor and molars to achieve experimental tooth movement. Rat grimace scale (RGS) scores were assessed at 0, 1, 3, 5, 7, and 14 days after the placement of the springs. ASIC3 immunostaining was performed and the expression levels of ASIC3 were measured through integrated optical density/area in Image-Pro Plus 6.0. Moreover, 18 rats were divided into APETx2 group (n = 6), amiloride group (n = 6), and vehicle group (n = 6), and RGS scores were obtained compared among them to verify the roles of ASIC3 in orofacial pain following tooth movement. ASIC3 expression levels became significantly higher in the experimental group than in sham group on 1, 3, and 5 days and became similar on 7 and 14 days. Pain levels (RGS scores) increased in both groups and were significantly higher in the experimental group on 1, 3, 5, and 7 days and were similar on 14 days. Periodontal ASIC3 expression levels were correlated with orofacial pain levels following experimental tooth movement. Periodontal administrations of ASIC3 antagonists (APETx2 and amiloride) could alleviate pain. This study needs to be better evidenced by RNA interference of ASIC3 in periodontal tissues in rats following experimental tooth movement. Moreover, we hope further studies would concentrate on the pain perception of ASIC3 knockout (ASIC3 -/- ) mice. Our results suggest that periodontal ASIC3 plays an important role in orofacial pain induced by experimental tooth movement. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  7. Influence of intramuscular granisetron on experimentally induced muscle pain by acidic saline.

    Science.gov (United States)

    Louca, S; Ernberg, M; Christidis, N

    2013-06-01

    The aim of this study was to investigate whether intramuscular administration of the 5-HT(3) receptor antagonist granisetron reduces experimental muscle pain induced by repeated intramuscular injections of acidic saline into the masseter muscles. Twenty-eight healthy and pain-free volunteers, fourteen women and fourteen men participated in this randomized, double-blind and placebo-controlled study. After a screening examination and registration of the baseline pressure-pain threshold (PPT), the first simultaneous bilateral injections of 0·5 mL acidic saline (9 mg mL(-1) , pH 3·3) into the masseter muscles were performed. Two days later, PPT and pain (VAS) were re-assessed. The masseter muscle was then pre-treated with 0·5 mL granisetron (Kytril(®) 1 mg mL(-1) pH 5·3) on one side and control substance (isotonic saline, 9 mg mL(-1) pH 6) on the contralateral side. Two minutes thereafter a bilateral simultaneous injection of 0·5 mL acidic saline followed. The evoked pain intensity, pain duration, pain area and PPT were assessed. The volunteers returned 1 week later to re-assess VAS and PPT. On the side pre-treated with granisetron, the induced pain had significantly lower intensity and shorter duration (P granisetron on pain duration was significant only in women (P granisetron has a pain-reducing effect on experimentally induced muscle pain by repeated acidic saline injection. © 2013 John Wiley & Sons Ltd.

  8. Neural correlates of heat-evoked pain memory in humans.

    Science.gov (United States)

    Wang, Liping; Gui, Peng; Li, Lei; Ku, Yixuan; Bodner, Mark; Fan, Gaojie; Zhou, Yong-Di; Dong, Xiao-Wei

    2016-03-01

    The neural processes underlying pain memory are not well understood. To explore these processes, contact heat-evoked potentials (CHEPs) were recorded in humans with electroencephalography (EEG) technique during a delayed matching-to-sample task, a working memory task involving presentations of two successive painful heat stimuli (S-1 and S-2) with different intensities separated by a 2-s interval (the memorization period). At the end of the task, the subject was required to discriminate the stimuli by indicating which (S-1 or S-2) induced more pain. A control task was used, in which no active discrimination was required between stimuli. All event-related potential (ERP) analysis was aligned to the onset of S-1. EEG activity exhibited two successive CHEPs: an N2-P2 complex (∼400 ms after onset of S-1) and an ultralate component (ULC, ∼900 ms). The amplitude of the N2-P2 at vertex, but not the ULC, was significantly correlated with stimulus intensity in these two tasks, suggesting that the N2-P2 represents neural coding of pain intensity. A late negative component (LNC) in the frontal recording region was observed only in the memory task during a 500-ms period before onset of S-2. LNC amplitude differed between stimulus intensities and exhibited significant correlations with the N2-P2 complex. These indicate that the frontal LNC is involved in maintenance of intensity of pain in working memory. Furthermore, alpha-band oscillations observed in parietal recording regions during the late delay displayed significant power differences between tasks. This study provides in the temporal domain previously unidentified neural evidence showing the neural processes involved in working memory of painful stimuli. Copyright © 2016 the American Physiological Society.

  9. Modulation of Itch by Conditioning Itch and Pain Stimulation in Healthy Humans.

    Science.gov (United States)

    Andersen, Hjalte H; van Laarhoven, Antoinette I M; Elberling, Jesper; Arendt-Nielsen, Lars

    2017-12-01

    Little is known about endogenous descending control of itch. In chronic pain, descending pain inhibition is reduced as signified by lowered conditioned pain modulation. There are indications that patients with chronic itch may also exhibit reduced endogenous descending inhibition of itch and pain. This study aimed to investigate whether and the extent to which itch can be modulated by conditioning itch and pain stimuli. Twenty-six healthy volunteers participated. The study consisted of 5 conditions designed to systematically assess endogenous modulation of itch or pain: 1) itch-induced modulation of contralateral itch, 2) pain-induced modulation of contralateral itch, 3) pain-induced modulation of ipsilateral itch, 4) pain-induced modulation of contralateral pain, and 5) itch-induced modulation of contralateral pain. Conditioning stimuli were cold pressor-induced pain and histamine-evoked itch, whereas the test stimuli were electrical stimulation paradigms designed to evoke itch or pain. Pain was significantly reduced (conditioned pain modulation-effect) by the conditioning pain stimulus (P modulation-effect) by contra- as well as ipsilateral applied conditioning pain (both P modulation of itch as well as pain in humans. Future studies addressing potential aberrations in pain-evoked descending modulation of itch in chronic itch patients are warranted. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

  10. A comparative behavioural study of mechanical hypersensitivity in 2 pain models in rats and humans.

    Science.gov (United States)

    Reitz, Marie-Céline; Hrncic, Dragan; Treede, Rolf-Detlef; Caspani, Ombretta

    2016-06-01

    The assessment of pain sensitivity in humans has been standardized using quantitative sensory testing, whereas in animals mostly paw withdrawal thresholds to diverse stimuli are measured. This study directly compares tests used in quantitative sensory testing (pinpricks, pressure algometer) with tests used in animal studies (electronic von Frey test: evF), which we applied to the dorsal hind limbs of humans after high frequency stimulation and rats after tibial nerve transection. Both experimental models induce profound mechanical hypersensitivity. At baseline, humans and rats showed a similar sensitivity to evF with 0.2 mm diameter tips, but significant differences for other test stimuli (all P pain models (P pain sensitivity, but probe size and shape should be standardized. Hypersensitivity to blunt pressure-the leading positive sensory sign after peripheral nerve injury in humans-is a novel finding in the tibial nerve transection model. By testing outside the primary zone of nerve damage (rat) or activation (humans), our methods likely involve effects of central sensitization in both species.

  11. Women with dysmenorrhoea are hypersensitive to experimentally induced forearm ischaemia during painful menstruation and during the pain-free follicular phase.

    Science.gov (United States)

    Iacovides, S; Avidon, I; Baker, F C

    2015-07-01

    Monthly primary dysmenorrhoeic pain is associated with increased sensitivity to painful stimuli, particularly in deep tissue. We investigated whether women with dysmenorrhoea, compared with controls, have increased sensitivity to experimentally induced deep-tissue muscle ischaemia in a body area distant from that of referred menstrual pain. The sub-maximal effort tourniquet test was used to induce forearm ischaemia in 11 women with severe dysmenorrhoea and in nine control women both during menstruation and in the follicular phase of the menstrual cycle. Von Frey hair assessments confirmed the presence of experimental ischaemia. Women rated the intensity of menstrual and ischaemic pain on a 100-mm visual analogue scale. Women with dysmenorrhoea [mean (SD): 68 (20) mm] reported significantly greater menstrual pain compared with controls [mean (SD): 2 (6) mm; p = 0.0001] during the menstruation phase. They also rated their forearm ischaemic pain as significantly greater than the controls during the menstruation [dysmenorrhoeics vs. controls mean (SD): 58 (19) mm vs. 31 (21) mm, p menstruation phase and pain-free follicular phase. These findings suggest the presence of long-lasting changes in muscle pain sensitivity in women with dysmenorrhoea. Our findings that dysmenorrhoeic women are hyperalgesic to a clinically relevant, deep-muscle ischaemic pain in areas outside of referred menstrual pain confirm other studies showing long-lasting changes in pain sensitivity outside of the painful period during menstruation. © 2014 European Pain Federation - EFIC®

  12. Effect of riluzole on acute pain and hyperalgesia in humans

    DEFF Research Database (Denmark)

    Hammer, N A; Lillesø, J; Pedersen, J L

    1999-01-01

    Riluzole modulates several transmitter systems which may be involved in nociception. Antinociceptive effects have been shown in animal studies, but there are no human data. Therefore, we have examined the acute analgesic effect of riluzole in a human model of inflammatory pain induced by a thermal...... injury on the distal leg (47 degrees C, 7 min, 12.5 cm2) in 20 healthy volunteers. Hyperalgesia to mechanical and heat stimuli were examined by von Frey hairs and thermodes. We used a randomized, double-blind, placebo-controlled design, and subjects received riluzole 100 mg or placebo for 2 days...

  13. A quantitative review of ethnic group differences in experimental pain response: do biology, psychology, and culture matter?

    Science.gov (United States)

    Rahim-Williams, Bridgett; Riley, Joseph L; Williams, Ameenah K K; Fillingim, Roger B

    2012-04-01

    Pain is a subjectively complex and universal experience. We examine research investigating ethnic group differences in experimental pain response and factors contributing to group differences. We conducted a systematic literature review and analysis of studies using experimental pain stimuli to assess pain sensitivity across multiple ethnic groups. Our search covered the period from 1944 to 2011, and used the PubMed bibliographic database; a reference source containing over 17 million citations. We calculated effect sizes; identified ethnic/racial group categories, pain stimuli, and measures; and examined findings regarding biopsychosociocultural factors contributing to ethnic/racial group differences. We found 472 studies investigating ethnic group differences and pain. Twenty-six of these met our review inclusion criteria of investigating ethnic group differences in experimental pain. The majority of studies included comparisons between African Americans (AA) and non-Hispanic Whites (NHW). There were consistently moderate to large effect sizes for pain tolerance across multiple stimulus modalities; AA demonstrated lower pain tolerance. For pain threshold, findings were generally in the same direction, but effect sizes were small to moderate across ethnic groups. Limited data were available for suprathreshold pain ratings. A subset of studies comparing NHW and other ethnic groups showed a variable range of effect sizes for pain threshold and tolerance. There are potentially important ethnic/racial group differences in experimental pain perception. Elucidating ethnic group differences has translational merit for culturally competent clinical care and for addressing and reducing pain treatment disparities among ethnically/racially diverse groups. Wiley Periodicals, Inc.

  14. Comparison of acceptance and distraction strategies in coping with experimentally induced pain

    Directory of Open Access Journals (Sweden)

    Moore H

    2015-03-01

    Full Text Available Hazel Moore,1 Ian Stewart,1 Dermot Barnes-Holmes,2 Yvonne Barnes-Holmes,2 Brian E McGuire1,31School of Psychology, National University of Ireland, Galway, 2Department of Psychology, National University of Ireland, Maynooth, 3Centre for Pain Research, National University of Ireland, Galway, IrelandBackground: This study compared an acceptance-based strategy with a control-based strategy (distraction in terms of the ability of participants to tolerate a painful stimulus, across two experiments. In addition, participants were either actively encouraged, or not, to link pain tolerance with pursuit of valued goals to examine the impact of pursuing a personally meaningful goal or value on the extent to which pain will be tolerated.Methods: Participants in experiment 1 (n=41 and experiment 2 (n=52 were equally assigned to acceptance or distraction protocols. Further, half the participants in each group generated examples from their own lives in which they had pursued a valued objective, while the other half did not. In experiment 2, the values focus was enhanced to examine the impact on pain tolerance.Results: There were no significant differences overall between the acceptance and distraction groups on pain tolerance in either experiment. However, in experiment 2, individuals classified as accepting in terms of general coping style and who were assigned to the acceptance strategy showed significantly better pain tolerance than accepting individuals who were in the distraction condition. Across both experiments, those with strong goal-driven values in both protocols were more tolerant of pain. Participants appeared to have more difficulty adhering to acceptance than to distraction as a strategy.Conclusion: Acceptance may be associated with better tolerance of pain, but may also be more difficult to operationalize than distraction in experimental studies. Matching coping style and coping strategy may be most effective, and enhancement of goal

  15. Preliminary findings of cerebral responses on transcutaneous vagal nerve stimulation on experimental heat pain.

    Science.gov (United States)

    Usichenko, Taras; Laqua, René; Leutzow, Bianca; Lotze, Martin

    2017-02-01

    Transcutaneous vagal nerve stimulation (TVNS) is a promising complementary method of pain relief. However, the neural networks associated with its analgesic effects are still to be elucidated. Therefore, we conducted two functional magnetic resonance imaging (fMRI) sessions, in a randomized order, with twenty healthy subjects who were exposed to experimental heat pain stimulation applied to the right forearm using a Contact Heat-Evoked Potential Stimulator. While in one session TVNS was administered bilaterally to the concha auriculae with maximal, non-painful intensity, the stimulation device was switched off in the other session (placebo condition). Pain thresholds were measured before and after each session. Heat stimulation elicited fMRI activation in cerebral pain processing regions. Activation magnitude in the secondary somatosensory cortex, posterior insula, anterior cingulate and caudate nucleus was associated with heat stimulation without TVNS. During TVNS, this association was only seen for the right anterior insula. TVNS decreased fMRI signals in the anterior cingulate cortex in comparison with the placebo condition; however, there was no relevant pain reducing effect over the group as a whole. In contrast, TVNS compared to the placebo condition showed an increased activation in the primary motor cortex, contralateral to the site of heat stimulation, and in the right amygdala. In conclusion, in the protocol used here, TVNS specifically modulated the cerebral response to heat pain, without having a direct effect on pain thresholds.

  16. Adaptability to pain is associated with potency of local pain inhibition, but not conditioned pain modulation: a healthy human study.

    Science.gov (United States)

    Zheng, Zhen; Wang, Kelun; Yao, Dongyuan; Xue, Charlie C L; Arendt-Nielsen, Lars

    2014-05-01

    This study investigated the relationship between pain sensitivity, adaptability, and potency of endogenous pain inhibition, including conditioned pain modulation (CPM) and local pain inhibition. Forty-one healthy volunteers (20 male, 21 female) received conditioning stimulation (CS) over 2 sessions in a random order: tonic heat pain (46 °C) on the right leg for 7 minutes and cold pressor pain (1 °C to 4 °C) on the left hand for 5 minutes. Participants rated the intensity of pain continuously using a 0 to 10 electronic visual analogue scale. The primary outcome measures were pressure pain thresholds (PPT) measured at the heterotopic and homotopic location to the CS sites before, during, and 20 minutes after CS. Two groups of participants, pain adaptive and pain nonadaptive, were identified based on their response to pain in the cold pressor test. Pain-adaptive participants showed a pain reduction between peak pain and pain at end of the test by at least 2 of 10 (n=16); whereas the pain-nonadaptive participants reported unchanged peak pain during 5-minute CS (n=25). Heterotopic PPTs during the CS did not differ between the 2 groups. However, increased homotopic PPTs measured 20 minutes after CS correlated with the amount of pain reduction during CS. These results suggest that individual sensitivity and adaptability to pain does not correlate with the potency of CPM. Adaptability to pain is associated with longer-lasting local pain inhibition. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  17. Effects of unilateral and bilateral experimental low-back pain on trunk muscle activity during stair walking in healthy and recurrent low-back pain patients

    DEFF Research Database (Denmark)

    Larsen, Lars Henrik; Hirata, Rogerio Pessoto; Graven-Nielsen, Thomas

    Aim To explore the trunk muscle activity in healthy and recurrent low back pain (R-LBP) patients with no present pain during stair ascent and descent before and after unilateral and bilateral experimental low back pain (LBP). Methods Twenty-five healthy controls and 25 pain-free R-LBP patients wi...... in the physical examination, but it remains unknown if the observed changes are appropriate strategies in relation to the pain condition. Acknowledgement The study was supported by CNAP, Aalborg University and UCN Department of physiotherapy, Denmark....

  18. TOLERANCE TIME OF EXPERIMENTAL THERMAL PAIN (COLD INDUCED) IN VOLUNTEERS.

    Science.gov (United States)

    Vaid, V N; Wilkhoo, N S; Jain, A K

    1998-10-01

    Perception of thermal pain (cold induced) was studied in 106 volunteers from troops and civilians deployed in J & K. Thermal stimulus devised was "holding ice". Tolerance time of holding ice was taken to be a measure of thermal sensitivity, volunteers were classified based on their native areas, addiction habits and socio-economic status, out of 106 volunteers, 81 could & 25 could not hold ice over 10 min. Sixteen out of 40 from coastline States and 9 out of 66 from non-coast line States failed to hold ice over 10 min. In "below average" "average" and "high average" socio-economic groups, three out of 27, 19 out of 73 and 03 out of 6 failed to hold ice over 10 min respectively. Fifteen out of 64 from "addiction habit group" and 10 out of 42 from "no addiction habit group" failed to hold ice over 10 min. Statistically no classification used in the study revealed significant difference in "tolerance times" of volunteers except the one based on coastline and non-coastline States.

  19. Investigation of the potentiation of the analgesic effects of fentanyl by ketamine in humans: a double-blinded, randomised, placebo controlled, crossover study of experimental pain[ISRCTN83088383

    Directory of Open Access Journals (Sweden)

    Nadeson Raymond

    2005-04-01

    Full Text Available Abstract Background Despite preclinical evidence suggesting a synergistic interaction between ketamine and opioids promoting analgesia, several clinical trials have not identified dosing regimens capable of eliciting a benefit in the co-administration of ketamine with opioids. Methods Ten healthy volunteers participated in a double blinded, randomised, placebo controlled, crossover laboratory study in order to determine whether a low dose of ketamine potentiated the antinociceptive effect of fentanyl without causing an increase in sedative effects. A battery of tests was used to assess both nociception and sedation including electrical current, pressure, thermal stimuli, psychometric tests, and both subjective and objective scores of sedation. Target controlled infusions of the study drugs were used. Ketamine and fentanyl were administered alone and in combination in a double-blinded randomised crossover design. Saline was used as the control, and propofol was used to validate the tests of sedation. Cardiovascular and respiratory parameters were also assessed. Results The electrical current pain threshold dose response curve of fentanyl combined with ketamine was markedly steeper than the dose response curve of fentanyl alone. While a ketamine serum concentration of 30 ng/ml did not result in a change in electrical pain threshold when administered alone, when it was added to fentanyl, the combination resulted in greater increase in pain threshold than that of fentanyl administered alone. When nociception was assessed using heat and pressure stimuli, ketamine did not potentiate the anti-nociceptive effect of fentanyl. There was no difference between the sedative effect of fentanyl and fentanyl in combination with ketamine as assessed by both subjective and objective measures of sedation. Cardiovascular and respiratory parameters were unaffected by the study drugs at the doses given. Conclusion A serum concentration of ketamine that did not alter

  20. Experimental pain leads to reorganisation of trapezius electromyography during computer work with active and passive pauses

    DEFF Research Database (Denmark)

    Samani, Afshin; Holtermann, Andreas; Søgaard, Karen

    2009-01-01

    The aim of this laboratory study was to investigate acute effects of experimental muscle pain on spatial electromyographic (EMG) activity of the trapezius muscle during computer work with active and passive pauses. Twelve healthy male subjects performed four sessions of computer work for 2 min...... in one day, with passive (relax) and active (30% maximum voluntary contraction of shoulder elevation) pauses given every 40 s without and with presence of experimental pain. Surface EMG signals were recorded from four parts of the trapezius. The centroid of exposure variation analysis along the time axis...... was lower during computer work with active pauses when compared with passive one in all muscle parts (P

  1. The effect of transcranial direct current stimulation on experimentally induced heat pain.

    Science.gov (United States)

    Aslaksen, Per M; Vasylenko, Olena; Fagerlund, Asbjørn J

    2014-06-01

    Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulatory technique that can affect human pain perception. Placebo effects are present in most treatments and could therefore also interact with treatment effects in tDCS. The present study investigated whether short-term tDCS reduced heat pain intensity, stress, blood pressure and increased heat pain thresholds in healthy volunteers when controlling for placebo effects. Seventy-five (37 females) participants were randomized into three groups: (1) active tDCS group receiving anodal tDCS (2 mA) for 7 min to the primary motor cortex (M1), (2) placebo group receiving the tDCS electrode montage but only active tDCS stimulation for 30 s and (3) natural history group that got no tDCS montage but the same pain stimulation as the active tDCS and the placebo group. Heat pain was induced by a PC-controlled thermode attached to the left forearm. Pain intensity was significantly lower in the active tDCS group when examining change scores (pretest-posttest) for the 47 °C condition. The placebo group displayed lower pain compared with the natural history group, displaying a significant placebo effect. In the 43 and 45 °C conditions, the effect of tDCS could not be separated from placebo effects. The results revealed no effects on pain thresholds. There was a tendency that active tDCS reduced stress and systolic blood pressure, however, not significant. In sum, tDCS had an analgesic effect on high-intensity pain, but the effect of tDCS could not be separated from placebo effects for medium and low pain.

  2. Attenuation of Experimental Pain by Vibro-Tactile Stimulation in Patients with Chronic Local or Widespread Musculoskeletal Pain

    OpenAIRE

    Staud, Roland; Robinson, Michael E.; Goldman, Casey T.; Price, Donald D.

    2011-01-01

    Patients with chronic pain syndromes, like fibromyalgia (FM) complain of widespread pain and tenderness, as well as non-refreshing sleep, cognitive dysfunction, and negative mood. Several lines of evidence implicate abnormalities of central pain processing as contributors for chronic pain, including dysfunctional descending pain inhibition. One form of endogenous pain inhibition, diffuse noxious inhibitory controls (DNIC), has been found to be abnormal in some chronic pain patients and eviden...

  3. The dynamics of the pain system is intact in patients with knee osteoarthritis: An exploratory experimental study.

    Science.gov (United States)

    Jørgensen, Tanja Schjødt; Henriksen, Marius; Rosager, Sara; Klokker, Louise; Ellegaard, Karen; Danneskiold-Samsøe, Bente; Bliddal, Henning; Graven-Nielsen, Thomas

    2017-12-29

    Background and aims Despite the high prevalence of knee osteoarthritis (OA) it remains one of the most frequent knee disorders without a cure. Pain and disability are prominent clinical features of knee OA. Knee OA pain is typically localized but can also be referred to the thigh or lower leg. Widespread hyperalgesia has been found in knee OA patients. In addition, patients with hyperalgesia in the OA knee joint show increased pain summation scores upon repetitive stimulation of the OA knee suggesting the involvement of facilitated central mechanisms in knee OA. The dynamics of the pain system (i.e., the adaptive responses to pain) has been widely studied, but mainly from experiments on healthy subjects, whereas less is known about the dynamics of the pain system in chronic pain patients, where the pain system has been activated for a long time. The aim of this study was to assess the dynamics of the nociceptive system quantitatively in knee osteoarthritis (OA) patients before and after induction of experimental knee pain. Methods Ten knee osteoarthritis (OA) patients participated in this randomized crossover trial. Each subject was tested on two days separated by 1 week. The most affected knee was exposed to experimental pain or control, in a randomized sequence, by injection of hypertonic saline into the infrapatellar fat pad and a control injection of isotonic saline. Pain areas were assessed by drawings on anatomical maps. Pressure pain thresholds (PPT) at the knee, thigh, lower leg, and arm were assessed before, during, and after the experimental pain and control conditions. Likewise, temporal summation of pressure pain on the knee, thigh and lower leg muscles was assessed. Results Experimental knee pain decreased the PPTs at the knee (P system in individuals with knee OA can be affected even after many years of nociceptive input. This study indicates that the adaptability in the pain system is intact in patients with knee OA, which opens for opportunities to

  4. Pharmacodynamic Modelling of Placebo and Buprenorphine Effects on Event-Related Potentials in Experimental Pain

    DEFF Research Database (Denmark)

    Juul, Rasmus V; Foster, David J R; Upton, Richard N

    2014-01-01

    The purpose of the study was to investigate placebo and buprenorphine effects on event-related potentials (ERPs) in experimental pain and the potential benefit of population pharmacodynamic modelling in data analysis. Nineteen healthy volunteers received transdermal placebo and buprenorphine...... in a cross-over study. Drug plasma concentrations and ERPs after electrical stimulation at the median nerve with intensity adjusted to pain detection threshold were recorded until 144 hrs after administration. Placebo and concentration-effect models were fitted to data using non-linear mixed......, pharmacodynamic modelling was successfully implemented to allow for placebo and variability correction in ERP of experimental pain. Improved outcome of ERP studies can be expected if variation between subjects and study occasions can be identified and described....

  5. Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain.

    Science.gov (United States)

    Bannister, Kirsty; Qu, Chaoling; Navratilova, Edita; Oyarzo, Janice; Xie, Jennifer Yanhua; King, Tamara; Dickenson, Anthony H; Porreca, Frank

    2017-12-01

    Gabapentin (GBP) is a first-line therapy for neuropathic pain, but its mechanisms and sites of action remain uncertain. We investigated GBP-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal GBP reversed evoked mechanical hypersensitivity and produced conditioned place preference (CPP) and dopamine (DA) release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal GBP also significantly inhibited dorsal horn wide-dynamic-range neuronal responses to a range of evoked stimuli in SNL rats. By contrast, GBP microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP, and elicited NAc DA release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on wide-dynamic-range neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous GBP-induced CPP and NAc DA release but failed to block its inhibition of tactile allodynia. Gabapentin, therefore, can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity, and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from nonopioid analgesics, GBP requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain-motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of GBP's analgesic effects in patients.

  6. Inhibition of TRPM8 channels reduces pain in the cold pressor test in humans.

    Science.gov (United States)

    Winchester, Wendy J; Gore, Katrina; Glatt, Sophie; Petit, Wendy; Gardiner, Jennifer C; Conlon, Kelly; Postlethwaite, Michael; Saintot, Pierre-Philippe; Roberts, Sonia; Gosset, James R; Matsuura, Tomomi; Andrews, Mark D; Glossop, Paul A; Palmer, Michael J; Clear, Nicola; Collins, Susie; Beaumont, Kevin; Reynolds, David S

    2014-11-01

    The transient receptor potential (subfamily M, member 8; TRPM8) is a nonselective cation channel localized in primary sensory neurons, and is a candidate for cold thermosensing, mediation of cold pain, and bladder overactivity. Studies with TRPM8 knockout mice and selective TRPM8 channel blockers demonstrate a lack of cold sensitivity and reduced cold pain in various rodent models. Furthermore, TRPM8 blockers significantly lower body temperature. We have identified a moderately potent (IC50 = 103 nM), selective TRPM8 antagonist, PF-05105679 [(R)-3-[(1-(4-fluorophenyl)ethyl)(quinolin-3-ylcarbonyl)amino]methylbenzoic acid]. It demonstrated activity in vivo in the guinea pig bladder ice water and menthol challenge tests with an IC50 of 200 nM and reduced core body temperature in the rat (at concentrations >1219 nM). PF-05105679 was suitable for acute administration to humans and was evaluated for effects on core body temperature and experimentally induced cold pain, using the cold pressor test. Unbound plasma concentrations greater than the IC50 were achieved with 600- and 900-mg doses. The compound displayed a significant inhibition of pain in the cold pressor test, with efficacy equivalent to oxycodone (20 mg) at 1.5 hours postdose. No effect on core body temperature was observed. An unexpected adverse event (hot feeling) was reported, predominantly periorally, in 23 and 36% of volunteers (600- and 900-mg dose, respectively), which in two volunteers was nontolerable. In conclusion, this study supports a role for TRPM8 in acute cold pain signaling at doses that do not cause hypothermia. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  7. Higher cortical modulation of pain perception in the human brain: Psychological determinant.

    Science.gov (United States)

    Chen, Andrew Cn

    2009-10-01

    Pain perception and its genesis in the human brain have been reviewed recently. In the current article, the reports on pain modulation in the human brain were reviewed from higher cortical regulation, i.e. top-down effect, particularly studied in psychological determinants. Pain modulation can be examined by gene therapy, physical modulation, pharmacological modulation, psychological modulation, and pathophysiological modulation. In psychological modulation, this article examined (a) willed determination, (b) distraction, (c) placebo, (d) hypnosis, (e) meditation, (f) qi-gong, (g) belief, and (h) emotions, respectively, in the brain function for pain modulation. In each, the operational definition, cortical processing, neuroimaging, and pain modulation were systematically deliberated. However, not all studies had featured the brain modulation processing but rather demonstrated potential effects on human pain. In our own studies on the emotional modulation on human pain, we observed that emotions could be induced from music melodies or pictures perception for reduction of tonic human pain, mainly in potentiation of the posterior alpha EEG fields, likely resulted from underneath activities of precuneous in regulation of consciousness, including pain perception. To sum, higher brain functions become the leading edge research in all sciences. How to solve the information bit of thinking and feeling in the brain can be the greatest challenge of human intelligence. Application of higher cortical modulation of human pain and suffering can lead to the progress of social humanity and civilization.

  8. The Effect of Experimental Parkinson on Formalin-Induced Pain in Rat

    Directory of Open Access Journals (Sweden)

    Mohammad Sofiabadi

    2014-04-01

    Full Text Available Background & Objectives : Pain is one of the preceding claims of Parkinson's disease (PD, that its mechanisms have not been fully identified. The purpose of this study was to investigate the chemical pain responses induced by subcutaneous injection of formalin in male parkinsonized rats.   Method : In this experimental study, 40 Wistar male rats were used and PD was established by stereotaxic injection of 6-OHDA toxin into the striatum. Parkinson's disease severity determined by apomorphine-induced rotation test and then the pain response of 4 groups, the control, sham and 2 weak or full Parkinson groups, were evaluated using formalin test. Data were analyzed using ANOVA and Tukey test.   Results : In both acute and chronic phases of the formalin test, the symptoms of pain in different groups were same, but at the interphase stage, pain intensity increased more in Parkinson 's rats, especially in full PD group compared to control (p<0.01.   Conclusion: These results suggest that the nigrostriatal dopaminergic pathway have important modulating role on chronic pain.

  9. Kinesthetic illusions attenuate experimental muscle pain, as do muscle and cutaneous stimulation.

    Science.gov (United States)

    Gay, André; Aimonetti, Jean-Marc; Roll, Jean-Pierre; Ribot-Ciscar, Edith

    2015-07-30

    In the present study, muscle pain was induced experimentally in healthy subjects by administrating hypertonic saline injections into the tibialis anterior (TA) muscle. We first aimed at comparing the analgesic effects of mechanical vibration applied to either cutaneous or muscle receptors of the TA or to both types simultaneously. Secondly, pain alleviation was compared in subjects in whom muscle tendon vibration evoked kinesthetic illusions of the ankle joint. Muscle tendon vibration, which primarily activated muscle receptors, reduced pain intensity by 30% (p<0.01). In addition, tangential skin vibration reduced pain intensity by 33% (p<0.01), primarily by activating cutaneous receptors. Concurrently stimulating both sensory channels induced stronger analgesic effects (-51%, p<0.01), as shown by the lower levels of electrodermal activity. The strongest analgesic effects of the vibration-induced muscle inputs occurred when illusory movements were perceived (-38%, p=0.01). The results suggest that both cutaneous and muscle sensory feedback reduce muscle pain, most likely via segmental and supraspinal processes. Further clinical trials are needed to investigate these new methods of muscle pain relief. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Neuropathic pain in experimental autoimmune neuritis is associated with altered electrophysiological properties of nociceptive DRG neurons.

    Science.gov (United States)

    Taha, Omneya; Opitz, Thoralf; Mueller, Marcus; Pitsch, Julika; Becker, Albert; Evert, Bernd Oliver; Beck, Heinz; Jeub, Monika

    2017-11-01

    Guillain-Barré syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy characterized by rapidly progressive paresis and sensory disturbances. Moderate to severe and often intractable neuropathic pain is a common symptom of GBS, but its underlying mechanisms are unknown. Pathology of GBS is classically attributed to demyelination of large, myelinated peripheral fibers. However, there is increasing evidence that neuropathic pain in GBS is associated with impaired function of small, unmyelinated, nociceptive fibers. We therefore examined the functional properties of small DRG neurons, the somata of nociceptive fibers, in a rat model of GBS (experimental autoimmune neuritis=EAN). EAN rats developed behavioral signs of neuropathic pain. This was accompanied by a significant shortening of action potentials due to a more rapid repolarization and an increase in repetitive firing in a subgroup of capsaicin-responsive DRG neurons. Na + current measurements revealed a significant increase of the fast TTX-sensitive current and a reduction of the persistent TTX-sensitive current component. These changes of Na + currents may account for the significant decrease in AP duration leading to an overall increase in excitability and are therefore possibly directly linked to pathological pain behavior. Thus, like in other animal models of neuropathic and inflammatory pain, Na + channels seem to be crucially involved in the pathology of GBS and may constitute promising targets for pain modulating pharmaceuticals. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain

    DEFF Research Database (Denmark)

    Hald, Andreas; Ding, Ming; Egerod, Kristoffer Lihme

    2008-01-01

    Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with can......Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment...... with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain...... and neuropathic pain in mice. In addition, we investigated the development of CNS related side effects and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related behavior and expression of spinal glial fibrillary acidic protein in the bone cancer pain model but not in the neuropathic pain model...

  12. Pain in adolescent girls receiving human papillomavirus vaccine with concomitantly administered vaccines.

    Science.gov (United States)

    Walter, Emmanuel B; Kemper, Alex R; Dolor, Rowena J; Dunne, Eileen F

    2015-02-01

    Using the Faces Pain Scale - Revised, we assessed injection site pain 10 minutes after vaccination in young females randomized to receive either quadrivalent human papillomavirus vaccine (HPV4) before or after concomitantly administered vaccines. Although pain was modestly more after HPV4 injection than after other vaccines, the pain intensity after HPV4 injection was significantly less in those who received HPV4 before receiving other concomitant vaccines.

  13. Complex muscular adaptation to perturbations after induction of experimental low back pain in healthy participants

    DEFF Research Database (Denmark)

    Larsen, Lars Henrik; Hirata, Rogerio Pessoto; Graven-Nielsen, Thomas

    2014-01-01

    Background and aims Spine stability is affected in low back (LB) pain and potentially by muscle fatigue and soreness. This study assessed motor control responses to unexpected surface perturbations during stance during experimental LB muscle pain combined with fatigue and muscle soreness. Methods...... Nineteen healthy participants were examined day 1-3 before and after bilateral injections of hypertonic saline into m. longissimus. Pain intensity was scored on a visual analogue scale (VAS). Day 2 included injections during post-exercise LB muscle fatigue and day 3 during delayed onset back muscle...... soreness (DOMS). Twenty perturbations were conducted randomly with tilts in sagittal and frontal plane or displacements in the frontal plane. Bilateral electromyography (EMG) was recorded from 12 trunk muscles. The root-mean-square (RMS-EMG) was extracted. Changes (DeltaRMS) and absolute changes (Delta...

  14. Complex regional pain syndrome (CRPS) or continuous unilateral distal experimental pain stimulation in healthy subjects does not bias visual attention towards one hemifield.

    Science.gov (United States)

    Filippopulos, Filipp M; Grafenstein, Jessica; Straube, Andreas; Eggert, Thomas

    2015-11-01

    In natural life pain automatically draws attention towards the painful body part suggesting that it interacts with different attentional mechanisms such as visual attention. Complex regional pain syndrome (CRPS) patients who typically report on chronic distally located pain of one extremity may suffer from so-called neglect-like symptoms, which have also been linked to attentional mechanisms. The purpose of the study was to further evaluate how continuous pain conditions influence visual attention. Saccade latencies were recorded in two experiments using a common visual attention paradigm whereby orientating saccades to cued or uncued lateral visual targets had to be performed. In the first experiment saccade latencies of healthy subjects were measured under two conditions: one in which continuous experimental pain stimulation was applied to the index finger to imitate a continuous pain situation, and one without pain stimulation. In the second experiment saccade latencies of patients suffering from CRPS were compared to controls. The results showed that neither the continuous experimental pain stimulation during the experiment nor the chronic pain in CRPS led to an unilateral increase of saccade latencies or to a unilateral increase of the cue effect on latency. The results show that unilateral, continuously applied pain stimuli or chronic pain have no or only very limited influence on visual attention. Differently from patients with visual neglect, patients with CRPS did not show strong side asymmetries of saccade latencies or of cue effects on saccade latencies. Thus, neglect-like clinical symptoms of CRPS patients do not involve the allocation of visual attention.

  15. Experimental orofacial pain and sensory deprivation lead to perceptual distortion of the face in healthy volunteers.

    Science.gov (United States)

    Dagsdóttir, Lilja Kristín; Skyt, Ina; Vase, Lene; Baad-Hansen, Lene; Castrillon, Eduardo; Svensson, Peter

    2015-09-01

    Patients suffering from persistent orofacial pain may sporadically report that the painful area feels "swollen" or "differently," a phenomenon that may be conceptualized as a perceptual distortion because there are no clinical signs of swelling present. Our aim was to investigate whether standardized experimental pain and sensory deprivation of specific orofacial test sites would lead to changes in the size perception of these face areas. Twenty-four healthy participants received either 0.2 mL hypertonic saline (HS) or local anesthetics (LA) into six regions (buccal, mental, lingual, masseter muscle, infraorbital and auriculotemporal nerve regions). Participants estimated the perceived size changes in percentage (0 % = no change, -100 % = half the size or +100 % = double the size), and somatosensory function was checked with tactile stimuli. The pain intensity was rated on a 0-10 Verbal Numerical Rating Scale (VNRS), and sets of psychological questionnaires were completed. HS and LA were associated with significant self-reported perceptual distortions as indicated by consistent increases in perceived size of the adjacent face areas (P ≤ 0.050). Perceptual distortion was most pronounced in the buccal region, and the smallest increase was observed in the auriculotemporal region. HS was associated with moderate levels of pain VNRS = 7.3 ± 0.6. Weak correlations were found between HS-evoked perceptual distortion and level of dissociation in two regions (P pain and transient sensory deprivation evoked perceptual distortions in all face regions and overall demonstrated the importance of afferent inputs for the perception of the face. We propose that perceptual distortion may be an important phenomenon to consider in persistent orofacial pain conditions.

  16. Increased circulating rather than spinal cytokines accompany chronic pain behaviors in experimental bone cancer and arthritis

    Directory of Open Access Journals (Sweden)

    Line Pourtau

    2014-12-01

    Full Text Available Aim: Peripheral cytokines contribute to arthritis and bone cancer pain through sensory nerve actions. However, increased spinal cytokine and glial filament expression, coined neuroinflammation, has also been proposed to play a part in chronic pain. Therefore, spinal cord, dorsal root ganglia and circulating cytokines were compared in murine arthritis and bone cancer models in relationship to behavioral signs of pain. Methods: Exploratory behaviors were studied after intra-articular complete Freund's adjuvant or bone intramedullary sarcoma cell injection. Nervous tissue and blood cytokine expression were determined by real-time polymerase chain reaction (PCR and multiplex immunoassays, respectively. Results: PCR analysis did not reveal any hallmark of spinal neuroinflammation in spontaneously-behaving mice with cartilage or bone lesions. However, imposed paw stimulation during joint inflammation increased spinal interleukin-1β (IL-1β expression. Spontaneous paw guarding during rearing was displayed by animals with joint inflammation and bone destruction and was accompanied by increased circulating IL-6 and monocyte chemoattractant protein-1, respectively. In addition, dorsal root ganglia were found to constitutively express receptors for this chemotactic cytokine. Conclusion: Our findings indicate that spinal neuroinflammation is not a necessary condition for chronic pain and suggest that circulating cytokine action in dorsal root ganglia may contribute to experimental joint inflammation and bone cancer pain.

  17. Prices need no preferences: social trends determine decisions in experimental markets for pain relief.

    Science.gov (United States)

    Vlaev, Ivo; Seymour, Ben; Chater, Nick; Winston, Joel S; Yoshida, Wako; Wright, Nicholas; Symmonds, Mkael; Dolan, Ray

    2014-01-01

    A standard view in health economics is that, although there is no market that determines the "prices" for health states, people can nonetheless associate health states with monetary values (or other scales, such as quality adjusted life year [QALYs] and disability adjusted life year [DALYs]). Such valuations can be used to shape health policy, and a major research challenge is to elicit such values from people; creating experimental "markets" for health states is a theoretically attractive way to address this. We explore the possibility that this framework may be fundamentally flawed-because there may not be any stable values to be revealed. Instead, perhaps people construct ad hoc values, influenced by contextual factors, such as the observed decisions of others. The participants bid to buy relief from equally painful electrical shocks to the leg and arm in an experimental health market based on an interactive second-price auction. Thirty subjects were randomly assigned to two experimental conditions where the bids by "others" were manipulated to follow increasing or decreasing price trends for one, but not the other, pain. After the auction, a preference test asked the participants to choose which pain they prefer to experience for a longer duration. Players remained indifferent between the two pain-types throughout the auction. However, their bids were differentially attracted toward what others bid for each pain, with overbidding during decreasing prices and underbidding during increasing prices. Health preferences are dissociated from market prices, which are strongly referenced to others' choices. This suggests that the price of health care in a free-market has the capacity to become critically detached from people's underlying preferences. 2014 APA, all rights reserved

  18. The Animal Model of Spinal Cord Injury as an Experimental Pain Model

    Directory of Open Access Journals (Sweden)

    Aya Nakae

    2011-01-01

    Full Text Available Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models.

  19. The Animal Model of Spinal Cord Injury as an Experimental Pain Model

    Science.gov (United States)

    Nakae, Aya; Nakai, Kunihiro; Yano, Kenji; Hosokawa, Ko; Shibata, Masahiko; Mashimo, Takashi

    2011-01-01

    Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models. PMID:21436995

  20. Higher cortical modulation of pain perception in the human brain: Psychological determinant

    OpenAIRE

    Chen, Andrew Cn

    2009-01-01

    Pain perception and its genesis in the human brain have been reviewed recently. In the current article, the reports on pain modulation in the human brain were reviewed from higher cortical regulation, i.e. top-down effect, particularly studied in psychological determinants. Pain modulation can be examined by gene therapy, physical modulation, pharmacological modulation, psychological modulation, and pathophysiological modulation. In psychological modulation, this article examined (a) willed d...

  1. Human embryonic stem cell lines model experimental human cytomegalovirus latency.

    Science.gov (United States)

    Penkert, Rhiannon R; Kalejta, Robert F

    2013-05-28

    Herpesviruses are highly successful pathogens that persist for the lifetime of their hosts primarily because of their ability to establish and maintain latent infections from which the virus is capable of productively reactivating. Human cytomegalovirus (HCMV), a betaherpesvirus, establishes latency in CD34(+) hematopoietic progenitor cells during natural infections in the body. Experimental infection of CD34(+) cells ex vivo has demonstrated that expression of the viral gene products that drive productive infection is silenced by an intrinsic immune defense mediated by Daxx and histone deacetylases through heterochromatinization of the viral genome during the establishment of latency. Additional mechanistic details about the establishment, let alone maintenance and reactivation, of HCMV latency remain scarce. This is partly due to the technical challenges of CD34(+) cell culture, most notably, the difficulty in preventing spontaneous differentiation that drives reactivation and renders them permissive for productive infection. Here we demonstrate that HCMV can establish, maintain, and reactivate in vitro from experimental latency in cultures of human embryonic stem cells (ESCs), for which spurious differentiation can be prevented or controlled. Furthermore, we show that known molecular aspects of HCMV latency are faithfully recapitulated in these cells. In total, we present ESCs as a novel, tractable model for studies of HCMV latency.

  2. Experimental tooth clenching. A model for studying mechanisms of muscle pain.

    Science.gov (United States)

    Dawson, Andreas

    2013-01-01

    The overall goal of this thesis was to broaden knowledge of pain mechanisms in myofascial temporomandibular disorders (M-TMD). The specific aims were to: Develop a quality assessment tool for experimental bruxism studies (study I). Investigate proprioceptive allodynia after experimental tooth clenching exercises (study II). Evaluate the release of serotonin (5-HT), glutamate, pyruvate, and lactate in healthy subjects (study III) and in patients with M-TMD (study IV), after experimental tooth clenching exercises. In (I), tool development comprised 5 steps: (i) preliminary decisions, (ii) item generation, (iii) face-validity assessment, (iv) reliability and discriminative validity testing, and (v) instrument refinement. After preliminary decisions and a literature review, a list of 52 items to be considered for inclusion in the tool was generated. Eleven experts were invited to participate on the Delphi panel, of which 10 agreed. After four Delphi rounds, 8 items remained and were included in the Quality Assessment Tool for Experimental Bruxism Studies (Qu-ATEBS). Inter-observer reliability was acceptable (k = 0.77), and discriminative validity high (phi coefficient 0.79; P < 0.01). During refinement, 1 item was removed; the final tool comprised 7 items. In (II), 16 healthy females participated in three 60-min sessions, each with 24- and 48-h follow-ups. Participants were randomly assigned to a repetitive experimental tooth clenching task with a clenching level of 10%, 20%, or 40% of maximal voluntary clenching force (MVCF). Pain intensity, fatigue, perceived intensity of vibration (PIV), perceived discomfort (PD), and pressure pain threshold (PPT) were measured throughout. A significant increase in pain intensity and fatigue but not in PD was observed over time. A significant increase in PIV was only observed at 40 min, and PPT decreased significantly over time at 50 and 60 min compared to baseline. In (III), 30 healthy subjects (16 females, and 14 males

  3. Experimental knee joint pain during strength training and muscle strength gain in healthy subjects: a randomized controlled trial.

    Science.gov (United States)

    Sørensen, T J; Langberg, H; Hodges, P W; Bliddal, H; Henriksen, M

    2012-01-01

    Knee joint pain and reduced quadriceps strength are cardinal symptoms in many knee pathologies. In people with painful knee pathologies, quadriceps exercise reduces pain, improves physical function, and increases muscle strength. A general assumption is that pain compromises muscle function and thus may prevent effective rehabilitation. This study evaluated the effects of experimental knee joint pain during quadriceps strength training on muscle strength gain in healthy individuals. Twenty-seven healthy untrained volunteers participated in a randomized controlled trial of quadriceps strengthening (3 times per week for 8 weeks). Participants were randomized to perform resistance training either during pain induced by injections of painful hypertonic saline (pain group, n = 13) or during a nonpainful control condition with injection of isotonic saline (control group, n = 14) into the infrapatellar fat pad. The primary outcome measure was change in maximal isokinetic muscle strength in knee extension/flexion (60, 120, and 180 degrees/second). The group who exercised with pain had a significantly larger improvement in isokinetic muscle strength at all angular velocities of knee extension compared to the control group. In knee flexion there were improvements in isokinetic muscle strength in both groups with no between-group differences. Experimental knee joint pain improved the training-induced gain in muscle strength following 8 weeks of quadriceps training. It remains to be studied whether knee joint pain has a positive effect on strength gain in patients with knee pathology. Copyright © 2012 by the American College of Rheumatology.

  4. Do intensity ratings and skin conductance responses reliably discriminate between different stimulus intensities in experimentally induced pain?

    Science.gov (United States)

    Breimhorst, Markus; Sandrock, Stephan; Fechir, Marcel; Hausenblas, Nadine; Geber, Christian; Birklein, Frank

    2011-01-01

    The present study addresses the question whether pain-intensity ratings and skin conductance responses (SCRs) are able to detect different intensities of phasic painful stimuli and to determine the reliability of this discrimination. For this purpose, 42 healthy participants of both genders were assigned to either electrical, mechanical, or laser heat-pain stimulation (each n = 14). A whole range of single brief painful stimuli were delivered on the right volar forearm of the dominant hand in a randomized order. Pain-intensity ratings and SCRs were analyzed. Using generalizability theory, individual and gender differences were the main contributors to the variability of both intensity ratings and SCRs. Most importantly, we showed that pain-intensity ratings are a reliable measure for the discrimination of different pain stimulus intensities in the applied modalities. The reliability of SCR was adequate when mechanical and heat stimuli were tested but failed for the discrimination of electrical stimuli. Further studies are needed to reveal the reason for this lack of accuracy for SCRs when applying electrical pain stimuli. Our study could help researchers to better understand the relationship between pain and activation of the sympathetic nervous system. Pain researchers are furthermore encouraged to consider individual and gender differences when measuring pain intensity and the concomitant SCRs in experimental settings. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

  5. Length of perineal pain relief after ice pack application: A quasi-experimental study.

    Science.gov (United States)

    de Souza Bosco Paiva, Caroline; Junqueira Vasconcellos de Oliveira, Sonia Maria; Amorim Francisco, Adriana; da Silva, Renata Luana; de Paula Batista Mendes, Edilaine; Steen, Mary

    2016-04-01

    Ice pack is effective for alleviating postpartum perineal pain in primiparous women while multiparous women's levels of perineal pain appear to be poorly explored. Ice pack is a low-cost non-invasive localised treatment that can be used with no impact on breastfeeding. However, how long perineal analgesia persists after applying an ice pack is still unknown. To evaluate if perineal analgesia is maintained up to 2h after applying an ice pack to the perineum for 20min. A quasi-experimental study, using a pre and post-test design, was undertaken with a sample size of 50 multiparous women in Brazil. Data was collected by structured interview. The intervention involved a single application of an ice pack applied for 20min to the perineal area of women who reported perineal pain ≥3 by use of a numeric rating scale (0-10), with intact perineum, 1st or 2nd degree lacerations or episiotomy, between 6 and 24h after spontaneous vaginal birth. Perineal pain was evaluated at three points of time: before, immediately after and 2h after applying an ice pack. Immediately after applying an ice pack to the perineal area, there was a significant reduction in the severity of perineal pain reported (5.4 vs. 1.0, p<0.0005), which continued for 1h 35min up to 2h after the local application. Ice pack application for 20min is effective for alleviating postpartum perineal pain and continues to be effective between 1h 35min for up to 2h. Copyright © 2015 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  6. Inhibition of c-Kit signaling is associated with reduced heat and cold pain sensitivity in humans.

    Science.gov (United States)

    Ceko, Marta; Milenkovic, Nevena; le Coutre, Philipp; Westermann, Jörg; Lewin, Gary R

    2014-07-01

    The tyrosine kinase receptor c-Kit is critically involved in the modulation of nociceptive sensitivity in mice. Ablation of the c-Kit gene results in hyposensitivity to thermal pain, whereas activation of c-Kit produces hypersensitivity to noxious heat, without altering sensitivity to innocuous mechanical stimuli. In this study, we investigated the role of c-Kit signaling in human pain perception. We hypothesized that subjects treated with Imatinib or Nilotinib, potent inhibitors of tyrosine kinases including c-Kit but also Abl1, PDFGFRα, and PDFGFRβ, that are used to treat chronic myeloid leukemia (CML), would experience changes in thermal pain sensitivity. We examined 31 asymptomatic CML patients (14 male and 17 female) receiving Imatinib/Nilotinib treatment and compared them to 39 age- and sex-matched healthy controls (12 male and 27 female). We used cutaneous heat and cold stimulation to test normal and noxious thermal sensitivity, and a grating orientation task to assess tactile acuity. Thermal pain thresholds were significantly increased in the Imatinib/Nilotinib-treated group, whereas innocuous thermal and tactile thresholds were unchanged compared to those in the control group. In conclusion, our findings suggest that the biological effects of c-Kit inhibition are comparable in mice and humans in that c-Kit activity is required to regulate thermal pain sensitivity but does not affect innocuous thermal and mechanical sensation. The effect on experimental heat pain observed in our study is comparable to those of several common analgesics; thus modulation of the c-Kit pathway can be used to specifically modulate noxious heat and cold sensitivity in humans. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  7. Remote Effects of Electromagnetic Millimeter Waves on Experimentally Induced Cold Pain: A Double-Blinded Crossover Investigation in Healthy Volunteers.

    Science.gov (United States)

    Partyla, Tomasz; Hacker, Henriette; Edinger, Hardy; Leutzow, Bianca; Lange, Joern; Usichenko, Taras

    2017-03-01

    The hypoalgesic effect of electromagnetic millimeter waves (MW) is well studied in animal model; however, the results of human research are controversial. The aim of this study was to evaluate the effects of various frequency ranges of MW on hypoalgesia using the cold pressor test (CPT). Experimental pain was induced using standardized CPT protocols in 20 healthy male volunteers. The skin of the lower part of sternum was exposed to MW with a frequency of 42.25 GHz (active generator); MW within 50-75 GHz frequency range (noise generator); or an inactive MW device (placebo generator) in a random crossover double-blinded manner. Pain threshold, measured using the CPT, was the primary outcome. Other CPT parameters, heart rate, blood pressure, incidence of subjective sensations (paresthesia) during exposure, as well as quality of volunteers' blinding were also recorded. The end points of the condition with exposure to 42.25 GHz, were compared with baseline; exposure to noise 50-75 GHz; and placebo generators. Pain threshold increased during exposure to the 42.25 GHz generator when compared with baseline: median difference (MD), 1.97 seconds (95% confidence interval [CI], 0.35-3.73) and noise generator: MD, 1.27 seconds (95% CI, 0.05-2.33) but not compared with the placebo generator. Time to onset of cold and increasing pain sensations as well as diastolic blood pressure increased under the exposure to the 42.25 GHz generator when compared with baseline and noise generator. Other outcome measures were comparable among the study conditions. We were able to partially confirm the previously suggested hypoalgesic effects of low-intensity electromagnetic MW. However, the effect was indistinguishable from the placebo condition in our investigation.

  8. The flaws and human harms of animal experimentation.

    Science.gov (United States)

    Akhtar, Aysha

    2015-10-01

    Nonhuman animal ("animal") experimentation is typically defended by arguments that it is reliable, that animals provide sufficiently good models of human biology and diseases to yield relevant information, and that, consequently, its use provides major human health benefits. I demonstrate that a growing body of scientific literature critically assessing the validity of animal experimentation generally (and animal modeling specifically) raises important concerns about its reliability and predictive value for human outcomes and for understanding human physiology. The unreliability of animal experimentation across a wide range of areas undermines scientific arguments in favor of the practice. Additionally, I show how animal experimentation often significantly harms humans through misleading safety studies, potential abandonment of effective therapeutics, and direction of resources away from more effective testing methods. The resulting evidence suggests that the collective harms and costs to humans from animal experimentation outweigh potential benefits and that resources would be better invested in developing human-based testing methods.

  9. Lack of influence of GTP cyclohydrolase gene (GCH1 variations on pain sensitivity in humans

    Directory of Open Access Journals (Sweden)

    Dionne Raymond A

    2007-03-01

    Full Text Available Abstract Objectives To assess the effect of variations in GTP cyclohydrolase gene (GCH1 on pain sensitivity in humans. Methods Thermal and cold pain sensitivity were evaluated in a cohort of 735 healthy volunteers. Among this cohort, the clinical pain responses of 221 subjects after the surgical removal of impacted third molars were evaluated. Genotyping was done for 38 single nucleotide polymorphisms (SNPs whose heterozygosity > 0.2 in GCH1. Influence of the genetic variations including SNPs and haplotypes on pain sensitivity were analyzed. Results Minor allele frequencies and linkage disequilibrium show significant differences in European Americans, African Americans, Hispanic Americans and Asian Americans. Association analyses in European Americans do not replicate the previously reported important influence of GCH1 variations on pain sensitivity. Conclusion Considering population stratification, previously reported associations between GCH1 genetic variations and pain sensitivity appear weak or negligible in this well characterized model of pain.

  10. Numbness in clinical and experimental pain--a cross-sectional study exploring the mechanisms of reduced tactile function.

    Science.gov (United States)

    Geber, Christian; Magerl, Walter; Fondel, Ricarda; Fechir, Marcel; Rolke, Roman; Vogt, Thomas; Treede, Rolf-Detlef; Birklein, Frank

    2008-09-30

    Pain patients often report distinct numbness of the painful skin although no structural peripheral or central nerve lesion is obvious. In this cross-sectional study we assessed the reduction of tactile function and studied underlying mechanisms in patients with chronic pain and in healthy participants exposed to phasic and tonic experimental nociceptive stimulation. Mechanical detection (MDT) and pain thresholds (MPT) were assessed in the painful area and the non-painful contralateral side in 10 patients with unilateral musculoskeletal pain. Additionally, 10 healthy participants were exposed to nociceptive stimulation applied to the volar forearms (capsaicin; electrical stimulation, twice each). Areas of tactile hypaesthesia and mechanical hyperalgesia were assessed. MDT and MPT were quantified adjacent to the stimulation site. Tactile hypaesthesia in pain patients and in experimental pain (MDT-z-scores: -0.66+/-0.30 and -0.42+/-0.15, respectively, both p<0.01) was paralleled by mechanical hyperalgesia (MPT-z-scores: +0.51+/-0.27, p<0.05; and +0.48+/-0.10, p<0.001). However, hypaesthesia and hyperalgesia were not correlated. Although 9 patients reported numbness, only 3 of them were able to delineate circumscript areas of tactile hypaesthesia. In experimental pain, the area of tactile hypaesthesia could be mapped in 31/40 experiments (78%). Irrespective of the mode of nociceptive stimulation (phasic vs. tonic) tactile hypaesthesia and hyperalgesia developed with a similar time course and disappeared within approximately 1 day. Hypaesthesia (numbness) often encountered in clinical pain can be reproduced by experimental nociceptive stimulation. The time course of effects suggests a mechanism involving central plasticity.

  11. Evolving robot empathy towards humans with motor disabilities through artificial pain generation

    Directory of Open Access Journals (Sweden)

    Muh Anshar

    2018-01-01

    Full Text Available In contact assistive robots, a prolonged physical engagement between robots and humans with motor disabilities due to shoulder injuries, for instance, may at times lead humans to experience pain. In this situation, robots will require sophisticated capabilities, such as the ability to recognize human pain in advance and generate counter-responses as follow up emphatic action. Hence, it is important for robots to acquire an appropriate pain concept that allows them to develop these capabilities. This paper conceptualizes empathy generation through the realization of synthetic pain classes integrated into a robot’s self-awareness framework, and the implementation of fault detection on the robot body serves as a primary source of pain activation. Projection of human shoulder motion into the robot arm motion acts as a fusion process, which is used as a medium to gather information for analyses then to generate corresponding synthetic pain and emphatic responses. An experiment is designed to mirror a human peer’s shoulder motion into an observer robot. The results demonstrate that the fusion takes place accurately whenever unified internal states are achieved, allowing accurate classification of synthetic pain categories and generation of empathy responses in a timely fashion. Future works will consider a pain activation mechanism development.

  12. Voluntary wheel running delays disease onset and reduces pain hypersensitivity in early experimental autoimmune encephalomyelitis (EAE).

    Science.gov (United States)

    Benson, Curtis; Paylor, John W; Tenorio, Gustavo; Winship, Ian; Baker, Glen; Kerr, Bradley J

    2015-09-01

    Multiple sclerosis (MS) is classically defined by motor deficits, but it is also associated with the secondary symptoms of pain, depression, and anxiety. Up to this point modifying these secondary symptoms has been difficult. There is evidence that both MS and the animal model experimental autoimmune encephalomyelitis (EAE), commonly used to study the pathophysiology of the disease, can be modulated by exercise. To examine whether limited voluntary wheel running could modulate EAE disease progression and the co-morbid symptoms of pain, mice with EAE were allowed access to running wheels for 1h every day. Allowing only 1h every day of voluntary running led to a significant delay in the onset of clinical signs of the disease. The development of mechanical allodynia was assessed using Von Frey hairs and indicated that wheel running had a modest positive effect on the pain hypersensitivity associated with EAE. These behavioral changes were associated with reduced numbers of cFOS and phosphorylated NR1 positive cells in the dorsal horn of the spinal cord compared to no-run EAE controls. In addition, within the dorsal horn, voluntary wheel running reduced the number of infiltrating CD3(+) T-cells and reduced the overall levels of Iba1 immunoreactivity. Using high performance liquid chromatography (HPLC), we observed that wheel-running lead to significant changes in the spinal cord levels of the antioxidant glutathione. Oxidative stress has separately been shown to contribute to EAE disease progression and neuropathic pain. Together these results indicate that in mice with EAE, voluntary motor activity can delay the onset of clinical signs and reduce pain symptoms associated with the disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Quality Improvement Project to Improve Patient Satisfaction With Pain Management: Using Human-Centered Design.

    Science.gov (United States)

    Trail-Mahan, Tracy; Heisler, Scott; Katica, Mary

    2016-01-01

    In this quality improvement project, our health system developed a comprehensive, patient-centered approach to improving inpatient pain management and assessed its impact on patient satisfaction across 21 medical centers. Using human-centered design principles, a bundle of 6 individual and team nursing practices was developed. Patient satisfaction with pain management, as measured by the Hospital Consumer Assessment of Healthcare Providers and Systems pain composite score, increased from the 25th to just under the 75th national percentile.

  14. Concept priming and pain: an experimental approach to understanding gender roles in sex-related pain differences.

    Science.gov (United States)

    Fowler, Stephanie L; Rasinski, Heather M; Geers, Andrew L; Helfer, Suzanne G; France, Christopher R

    2011-04-01

    Prior research has found that sex differences in pain are partially due to individual variations in gender roles. In a laboratory study, we tested the hypothesis that the presence of covert gender role cues can also moderate the extent to which women and men experience pain. Specifically, we varied gender role cues by asking male and female participants to write about instances in which they behaved in a stereotypically feminine, masculine, or neutral manner. Pain and cardiovascular reactivity to the cold pressor task were then assessed. Results revealed that, when primed with femininity, men reported less pain and anxiety from the cold pressor task than women. However, no differences existed between the sexes in the masculine or neutral prime conditions. The results indicate that covert gender cues can alter pain reports. Further, at least in some situations, feminine role cues may be more influential on pain reports than masculine role cues.

  15. Humans, but not animals, perceive the thermal grill illusion as painful.

    Science.gov (United States)

    Boettger, Michael K; Ditze, Günter; Bär, Karl-Juergen; Krüdewagen, Eva Maria; Schaible, Hans-Georg

    2016-10-15

    Simultaneous presentation of alternating innocuous warm and cold stimuli induces in most humans a painful sensation called thermal grill illusion (TGI). Here, pain is elicited although nociceptors are not activated. Upon back-translation of behavioural correlates from humans to animals, we found that neither cats nor rodents show adverse reactions when exposed to TGI stimulation. These results question that a TGI observed as a pain-related change in behaviour can be elicited in animals. While distinct neuronal patterns as previously reported may be measurable in animals upon TGI stimulation, their translational meaning towards the sensation elicited in humans is unclear. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. A word expressing affective pain activates the anterior cingulate cortex in the human brain: an fMRI study.

    Science.gov (United States)

    Osaka, Naoyuki; Osaka, Mariko; Morishita, Masanao; Kondo, Hirohito; Fukuyama, Hidenao

    2004-08-12

    We present an fMRI study demonstrating that an onomatopoeia word highly suggestive of subjective pain, heard by the ear, significantly activates the anterior cingulate cortex (ACC) while hearing non-sense words that did not imply affective pain under the same task does not activate this area in humans. We concluded that the ACC would be a pivotal locus for perceiving affective pain evoked by an onomatopoeia word that implied affective pain closely associated with the unpleasantness of pain. We suggest that the pain affect sustained by pain unpleasantness may depend on ACC-prefrontal cortical interactions that modify cognitive evaluation of emotions associated with word-induced pain.

  17. Human Immune Responses to Experimental Vaccinia Vaccines

    National Research Council Canada - National Science Library

    Ennis, Francis

    1996-01-01

    .... During the two years of this contract we have: (1) obtained, separated and cryopreserved peripheral blood mononuclear cells from 92 vaccinees in a clinical study to compare the standard and an experimental small pox vaccine, (2...

  18. Venlafaxine and Oxycodone Effects on Human Spinal and Supraspinal Pain Processing

    DEFF Research Database (Denmark)

    Lelic, D; Fischer, I W D; Olesen, Anne Estrup

    2016-01-01

    affect spinal and supraspinal pain processing. Twenty volunteers were included in this randomized cross-over study comparing 5-day treatment with venlafaxine, oxycodone and placebo. As a proxy of the spinal pain transmission, the nociceptive withdrawal reflex (NWR) to electrical stimulation on the sole......Severe pain is often treated with opioids. Antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) have also shown a pain relieving effect, but for both SNRI and opioids, the specific mode of action in humans remains vague. This study investigated how oxycodone and venlafaxine...

  19. Sacroiliac joint pain: Prospective, randomised, experimental and comparative study of thermal radiofrequency with sacroiliac joint block.

    Science.gov (United States)

    Cánovas Martínez, L; Orduña Valls, J; Paramés Mosquera, E; Lamelas Rodríguez, L; Rojas Gil, S; Domínguez García, M

    2016-05-01

    To compare the analgesic effects between the blockade and bipolar thermal radiofrequency in the treatment of sacroiliac joint pain. Prospective, randomised and experimental study conducted on 60 patients selected in the two hospitals over a period of nine months, who had intense sacroiliac joint pain (Visual Analogue Scale [VAS]>6) that lasted more than 3 months. Patients were randomised into three groups (n=20): Group A (two intra-articular sacroiliac injections of local anaesthetic/corticosteroid guided by ultrasound in 7 days). Group B: conventional bipolar radiofrequency "palisade". Target points were the lateral branch nerves of S1, S2, and S3, distance needles 1cm. Group C: modified bipolar radiofrequency "palisade" (needle distance >1cm). Patients were evaluated at one month, three months, and one year. Demographic data, VAS reduction, and side effects of the techniques were assessed. One month after the treatment, pain reduction was >50% in the three groups PDolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Multidimensional study of orofacial chronic neuropathic pain: An experimental study in rats.

    Directory of Open Access Journals (Sweden)

    Claudia Daniela Montes-Angeles

    2017-10-01

    Full Text Available Orofacial neuropathic chronic pain (NCP is frequently attributed to lesions caused by orofacial surgeries and dental treatments. There are many experimental models available to study orofacial NCP, however, many are extremely painful for the animal due to the amplitude of the innervated region. A previously proposed mental nerve constriction model, mNC, was used in this project. Forty Wistar rats were randomly divided into two groups: one group included rats with mNC (n=20, and another rats with sham lesions (n=20. Through the use of the fixed ratio program and the progressive program, a decrease of motivation for a sweet substance, caused by the lesion, was evaluated. The possibility of alterations in cognitive learning and adaptation abilities was also assessed using the go/no-go behavioral task. The mNC group showed low induced and spontaneously evoked pain responses, as well as a decrease in the motivation for sucrose, a sign of anhedonia. This decrease does not depend on taste processing. Finally, although no alterations in the learning-memory process were observed, the mNC group did show alterations when adapting to a new rule.

  1. Chronic Pelvic Pain Development and Prostate Inflammation in Strains of Mice With Different Susceptibility to Experimental Autoimmune Prostatitis.

    Science.gov (United States)

    Breser, Maria L; Motrich, Ruben D; Sanchez, Leonardo R; Rivero, Virginia E

    2017-01-01

    Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate-specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). EAP was induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus complete Freund́s adjuvant. Tactile allodynia was assessed using Von Frey fibers as a measure of pelvic pain at baseline and at different time points after immunization. Using conventional histology, immunohistochemistry, FACS analysis, and protein arrays, an interstrain comparative study of prostate cell infiltration and inflammation was performed. Chronic pelvic pain development was similar between immunized NOD and C57BL/6 mice, although the severity of leukocyte infiltration was greater in the first case. Coversely, minimal prostate cell infiltration was observed in immunized BALB/c mice, who showed no pelvic pain development. Increased numbers of mast cells, mostly degranulated, were detected in prostate samples from NOD and C57BL/6 mice, while lower total counts and resting were observed in BALB/c mice. Prostate tissue from NOD mice revealed markedly increased expression levels of inflammatory cytokines, chemokines, adhesion molecules, vascular endothelial growth factor, and metalloproteinases. Similar results, but to a lesser extent, were observed when analyzing prostate tissue from C57BL/6 mice. On the contrary, the expression of the above mediators was very low in prostate tissue from immunized BALB/c mice, showing significantly slight increments only for CXCL1 and IL4. Our results provide new evidence indicating that NOD, C57BL/6, and BALB/c mice develop different degrees of chronic pelvic pain, type, and amount of prostate cell infiltration

  2. VICTORIA Class Submarine Human-in-the-Loop Experimentation Plan

    Science.gov (United States)

    2014-06-01

    1472G. VICTORIA Class Submarine Human-in-the-Loop Experimentation Plan and Preliminary Results © Her Majesty the Queen in Right of...19 th International Command and Control Research and Technology Symposium Title: VICTORIA Class Submarine Human-in-the-Loop...TYPE 3. DATES COVERED 00-00-2014 to 00-00-2014 4. TITLE AND SUBTITLE VICTORIA Class Submarine Human-in-the-Loop Experimentation Plan 5a. CONTRACT

  3. Symptoms of Fibromyalgia According to the 2016 Revised Fibromyalgia Criteria in Chronic Pain Patients Referred to Multidisciplinary Pain Rehabilitation: Influence on Clinical and Experimental Pain Sensitivity

    DEFF Research Database (Denmark)

    Plesner, Karin Bruun; Vaegter, Henrik Bjarke

    2018-01-01

    Fibromyalgia is a condition with chronic widespread pain and signs of generalized pain hypersensitivity. FM has previously been classified according to the ACR1990 criteria, where the presence of hypersensitivity is estimated by a tender point examination. Due to the limitations of these classifi......Fibromyalgia is a condition with chronic widespread pain and signs of generalized pain hypersensitivity. FM has previously been classified according to the ACR1990 criteria, where the presence of hypersensitivity is estimated by a tender point examination. Due to the limitations...... of these classification criteria, new diagnostic criteria have been proposed, abandoning this examination. This cross-sectional study investigated the prevalence of FM according to the revised 2016 FM criteria in a large cohort of chronic pain patients. Pain drawings, the Fibromyalgia Symptom Severity Scale...

  4. Pain

    OpenAIRE

    H.W. Snyman

    1980-01-01

    The medical profession has always been under pressure to supply public explanations of the diseases with which it deals. On the other hand, it is an old characteristic of the profession to devise comprehensive and unifying theories on all sorts of medical problems. Both these statements apply to pain - one of the most important and clinically striking phenomena and expressions of man since his origin in the mists of time.

  5. Pain

    Directory of Open Access Journals (Sweden)

    H.W. Snyman

    1980-09-01

    Full Text Available The medical profession has always been under pressure to supply public explanations of the diseases with which it deals. On the other hand, it is an old characteristic of the profession to devise comprehensive and unifying theories on all sorts of medical problems. Both these statements apply to pain - one of the most important and clinically striking phenomena and expressions of man since his origin in the mists of time.

  6. Does experimental low back pain change posteroanterior lumbar spinal stiffness and trunk muscle activity? A randomized crossover study.

    Science.gov (United States)

    Wong, Arnold Y L; Parent, Eric C; Prasad, Narasimha; Huang, Christopher; Chan, K Ming; Kawchuk, Gregory N

    2016-05-01

    While some patients with low back pain demonstrate increased spinal stiffness that decreases as pain subsides, this observation is inconsistent. Currently, the relation between spinal stiffness and low back pain remains unclear. This study aimed to investigate the effects of experimental low back pain on temporal changes in posteroanterior spinal stiffness and concurrent trunk muscle activity. In separate sessions five days apart, nine asymptomatic participants received equal volume injections of hypertonic or isotonic saline in random order into the L3-L5 interspinous ligaments. Pain intensity, spinal stiffness (global and terminal stiffness) at the L3 level, and the surface electromyographic activity of six trunk muscles were measured before, immediately after, and 25-minute after injections. These outcome measures under different saline conditions were compared by generalized estimating equations. Compared to isotonic saline injections, hypertonic saline injections evoked significantly higher pain intensity (mean difference: 5.7/10), higher global (mean difference: 0.73N/mm) and terminal stiffness (mean difference: 0.58N/mm), and increased activity of four trunk muscles during indentation (Ppain subsided. While previous clinical research reported inconsistent findings regarding the association between spinal stiffness and low back pain, our study revealed that experimental pain caused temporary increases in spinal stiffness and concurrent trunk muscle co-contraction during indentation, which helps explain the temporal relation between spinal stiffness and low back pain observed in some clinical studies. Our results substantiate the role of spinal stiffness assessments in monitoring back pain progression. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Masticatory sensory-motor changes after an experimental chewing test influenced by pain catastrophizing and neck-pain-related disability in patients with headache attributed to temporomandibular disorders.

    Science.gov (United States)

    La Touche, Roy; Paris-Alemany, Alba; Gil-Martínez, Alfonso; Pardo-Montero, Joaquín; Angulo-Díaz-Parreño, Santiago; Fernández-Carnero, Josué

    2015-03-05

    Recent research has shown a relationship of craniomandibular disability with neck-pain-related disability has been shown. However, there is still insufficient information demonstrating the influence of neck pain and disability in the sensory-motor activity in patients with headache attributed to temporomandibular disorders (TMD). The purpose of this study was to investigate the influence of neck-pain-related disability on masticatory sensory-motor variables. An experimental case-control study investigated 83 patients with headache attributed to TMD and 39 healthy controls. Patients were grouped according to their scores on the neck disability index (NDI) (mild and moderate neck disability). Initial assessment included the pain catastrophizing scale and the Headache Impact Test-6. The protocol consisted of baseline measurements of pressure pain thresholds (PPT) and pain-free maximum mouth opening (MMO). Individuals were asked to perform the provocation chewing test, and measurements were taken immediately after and 24 hours later. During the test, patients were assessed for subjective feelings of fatigue (VAFS) and pain intensity. VAFS was higher at 6 minutes (mean 51.7; 95% CI: 50.15-53.26) and 24 hours after (21.08; 95% CI: 18.6-23.5) for the group showing moderate neck disability compared with the mild neck disability group (6 minutes, 44.16; 95% CI 42.65-45.67/ 24 hours after, 14.3; 95% CI: 11.9-16.7) and the control group. The analysis shows a decrease in the pain-free MMO only in the group of moderate disability 24 hours after the test. PPTs of the trigeminal region decreased immediately in all groups, whereas at 24 hours, a decrease was observed in only the groups of patients. PPTs of the cervical region decreased in only the group with moderate neck disability 24 hours after the test. The strongest negative correlation was found between pain-free MMO immediately after the test and NDI in both the mild (r = -0.49) and moderate (r = -0.54) neck disability

  8. Human Mendelian pain disorders: a key to discovery and validation of novel analgesics.

    Science.gov (United States)

    Goldberg, Y P; Pimstone, S N; Namdari, R; Price, N; Cohen, C; Sherrington, R P; Hayden, M R

    2012-10-01

    We have utilized a novel application of human genetics, illuminating the important role that rare genetic disorders can play in the development of novel drugs that may be of relevance for the treatment of both rare and common diseases. By studying a very rare Mendelian disorder of absent pain perception, congenital indifference to pain, we have defined Nav1.7 (endocded by SCN9A) as a critical and novel target for analgesic development. Strong human validation has emerged with SCN9A gain-of-function mutations causing inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder, both Mendelian disorder of spontaneous or easily evoked pain. Furthermore, variations in the Nav1.7 channel also modulate pain perception in healthy subjects as well as in painful conditions such as osteoarthritis and Parkinson disease. On the basis of this, we have developed a novel compound (XEN402) that exhibits potent, voltage-dependent block of Nav1.7. In a small pilot study, we showed that XEN402 blocks Nav1.7 mediated pain associated with IEM thereby demonstrating the use of rare genetic disorders with mutant target channels as a novel approach to rapid proof-of-concept. Our approach underscores the critical role that human genetics can play by illuminating novel and critical pathways pertinent for drug discovery. © 2012 John Wiley & Sons A/S.

  9. Effects of gabapentin in acute inflammatory pain in humans

    DEFF Research Database (Denmark)

    Werner, M U; Perkins, F M; Holte, Kathrine

    2001-01-01

    ,200 mg or placebo was given on 2 separate study days. Three hours after drug administration, a first-degree burn injury was produced on the medial aspect of the nondominant calf (12.5 cm(2), 47 degrees C for 7 minutes). Quantitative sensory testing (QST) included pain ratings to thermal and mechanical...

  10. Experimentally induced masseter-pain changes masseter but not sternocleidomastoid muscle-related activity during mastication.

    Science.gov (United States)

    Pasinato, Fernanda; Santos-Couto-Paz, Clarissa C; Zeredo, Jorge Luis Lopes; Macedo, Sergio Bruzadelli; Corrêa, Eliane C R

    2016-12-01

    The aim of this study was to verify the effects of induced masseter-muscle pain on the amplitude of muscle activation, symmetry and coactivation of jaw- and neck-muscles during mastication. Twenty-eight male volunteers, mean age±SD 20.6±2.0years, participated in this study. Surface electromyography of the masseter and sternocleidomastoid (SCM) muscles was performed bilaterally during mastication of a gummy candy before and after injections of monosodium glutamate solution and isotonic saline solution. As a result, we observed a decrease in the amplitude of activation of the masseter muscle on the working side (p=0.009; d=0.34) and a reduction in the asymmetry between the working and the balancing side during mastication (p=0.007; d=0.38). No changes were observed either on the craniocervical electromyographic variables. In conclusion, experimentally induced pain reduced the masseter muscle activation on the working side, thereby reducing the physiological masseters' recruitment asymmetry between the two sides during mastication. No effects on SCM activity were detected. These results may partly explain the initial maladaptative changes underlying TMD conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Preventing Chronic Pain: A Human Systems Approach-Results From a Massive Open Online Course.

    Science.gov (United States)

    Fricton, James; Anderson, Kathleen; Clavel, Alfred; Fricton, Regina; Hathaway, Kate; Kang, Wenjun; Jaeger, Bernadette; Maixner, William; Pesut, Daniel; Russell, Jon; Weisberg, Mark B; Whitebird, Robin

    2015-09-01

    Chronic pain conditions are the top reason patients seek care, the most common reason for disability and addiction, and the biggest driver of healthcare costs; their treatment costs more than cancer, heart disease, dementia, and diabetes care. The personal impact in terms of suffering, disability, depression, suicide, and other problems is incalculable. There has been much effort to prevent many medical and dental conditions, but little effort has been directed toward preventing chronic pain. To address this deficit, a massive open online course (MOOC) was developed for students and healthcare professionals. "Preventing Chronic Pain: A Human Systems Approach" was offered by the University of Minnesota through the online platform Coursera. The first offering of this free open course was in the spring of 2014 and had 23 650 participants; 53% were patients or consumers interested in pain. This article describes the course concepts in preventing chronic pain, the analytic data from course participants, and postcourse evaluation forms.

  12. Unraveling dynamics of human physical activity patterns in chronic pain conditions

    Science.gov (United States)

    Paraschiv-Ionescu, Anisoara; Buchser, Eric; Aminian, Kamiar

    2013-06-01

    Chronic pain is a complex disabling experience that negatively affects the cognitive, affective and physical functions as well as behavior. Although the interaction between chronic pain and physical functioning is a well-accepted paradigm in clinical research, the understanding of how pain affects individuals' daily life behavior remains a challenging task. Here we develop a methodological framework allowing to objectively document disruptive pain related interferences on real-life physical activity. The results reveal that meaningful information is contained in the temporal dynamics of activity patterns and an analytical model based on the theory of bivariate point processes can be used to describe physical activity behavior. The model parameters capture the dynamic interdependence between periods and events and determine a `signature' of activity pattern. The study is likely to contribute to the clinical understanding of complex pain/disease-related behaviors and establish a unified mathematical framework to quantify the complex dynamics of various human activities.

  13. Optimization of experimental human leukemia models (review

    Directory of Open Access Journals (Sweden)

    D. D. Pankov

    2012-01-01

    Full Text Available Actual problem of assessing immunotherapy prospects including antigenpecific cell therapy using animal models was covered in this review.Describe the various groups of currently existing animal models and methods of their creating – from different immunodeficient mice to severalvariants of tumor cells engraftment in them. The review addresses the possibility of tumor stem cells studying using mouse models for the leukemia treatment with adoptive cell therapy including WT1. Also issues of human leukemia cells migration and proliferation in a mice withdifferent immunodeficiency degree are discussed. To assess the potential immunotherapy efficacy comparison of immunodeficient mouse model with clinical situation in oncology patients after chemotherapy is proposed.

  14. Effects of Hemibridge with Ball and Balloon Exercise on Forced Expiratory Volume and Pain in Patients with Chronic Low Back Pain: An Experimental Study

    Directory of Open Access Journals (Sweden)

    Jorida Fernandes

    2017-08-01

    Full Text Available Background and objectives: Suboptimal breathing patterns and impairments of posture and trunk stability are often associated with musculoskeletal complaints such as low back pain. Respiration is also affected by poor neuromuscular control of core muscles. Immediate effects of hemibridge with ball and balloon exercise has been studied on chronic pain in athlete population. Objective: To evaluate the effects of hemibridge with ball and balloon exercise on pain, forced expiratory volume and functional abilities in patients with chronic low back pain using Visual Analogue Scale (VAS, Forced Expiratory Volume (FEV and Modified Oswestry Disability Questionnaire (MODQ. Methods: The present experimental study was conducted among 30 participants between the age of 21 to 55 years with chronic non-specific LBP. The participants were given a hemibridge with ball and balloon exercise. Pre-interventional and 3rd day Post-interventional outcome measurements were taken using VAS, FEV1 and FEV6 and MODQ. Results: The difference between pre-and post of VAS was statistically highly significant (p=0.0001. The p value of FEV6 and MODQ by paired t test was statistically significant with p value of 0.02 and 0.0007 respectively. Conclusion: The study concludes that there is an immediate effect of hemibridge with ball and balloon exercise on pain, FEV6 and functional ability in patients with chronic LBP.

  15. Nav1.7 expression is increased in painful human dental pulp

    Directory of Open Access Journals (Sweden)

    Levinson S Rock

    2008-04-01

    Full Text Available Abstract Background Animal studies and a few human studies have shown a change in sodium channel (NaCh expression after inflammatory lesions, and this change is implicated in the generation of pain states. We are using the extracted human tooth as a model system to study peripheral pain mechanisms and here examine the expression of the Nav1.7 NaCh isoform in normal and painful samples. Pulpal sections were labeled with antibodies against: 1 Nav1.7, N52 and PGP9.5, and 2 Nav1.7, caspr (a paranodal protein used to identify nodes of Ranvier, and myelin basic protein (MBP, and a z-series of optically-sectioned images were obtained with the confocal microscope. Nav1.7-immunofluorescence was quantified in N52/PGP9.5-identified nerve fibers with NIH ImageJ software, while Nav1.7 expression in myelinated fibers at caspr-identified nodal sites was evaluated and further characterized as either typical or atypical as based on caspr-relationships. Results Results show a significant increase in nerve area with Nav1.7 expression within coronal and radicular fiber bundles and increased expression at typical and atypical caspr-identified nodal sites in painful samples. Painful samples also showed an augmentation of Nav1.7 within localized areas that lacked MBP, including those associated with atypical caspr-identified sites, thus identifying NaCh remodeling within demyelinating axons as the basis for a possible pulpal pain mechanism. Conclusion This study identifies the increased axonal expression and augmentation of Nav1.7 at intact and remodeling/demyelinating nodes within the painful human dental pulp where these changes may contribute to constant, increased evoked and spontaneous pain responses that characterize the pain associated with toothache.

  16. Antinociceptive effect of intrathecal microencapsulated human pheochromocytoma cell in a rat model of bone cancer pain.

    Science.gov (United States)

    Li, Xiao; Li, Guoqi; Wu, Shaoling; Zhang, Baiyu; Wan, Qing; Yu, Ding; Zhou, Ruijun; Ma, Chao

    2014-07-08

    Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l) lysine-alginate (APA) microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.

  17. Antinociceptive Effect of Intrathecal Microencapsulated Human Pheochromocytoma Cell in a Rat Model of Bone Cancer Pain

    Directory of Open Access Journals (Sweden)

    Xiao Li

    2014-07-01

    Full Text Available Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l lysine-alginate (APA microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.

  18. Duration and distribution of experimental muscular hyperalgesia in humans following combined infusions of serotonin and bradykinin

    DEFF Research Database (Denmark)

    Babenko, Victor; Svensson, Peter; Graven-Nielsen, Thomas

    2000-01-01

    -infusions interval of 3 min. Infusions of isotonic saline (NaCl, 0.9%) were given as control. Pain intensity was continuously scored on a visual analogue scale (VAS), and subjects drew the distribution of the pain areas on an anatomical map. Pressure pain thresholds (PPTs) were assessed with an electronic algometer....... In addition, PPTs were significantly decreased (Peffect of bradykinin in producing experimental muscle pain and muscle hyperalgesia to mechanical stimuli. The combination of serotonin and bradykinin can produce muscle...

  19. EXPERIMENTAL SEMIOTICS: AN ENGINE OF DISCOVERY FOR UNDERSTANDING HUMAN COMMUNICATION

    OpenAIRE

    BRUNO GALANTUCCI; GARETH ROBERTS

    2012-01-01

    The recent growth of Experimental Semiotics (ES) offers us a new option to investigate human communication. We briefly introduce ES, presenting results from three themes of research which emerged within it. Then we illustrate the contribution ES can make to the investigation of human communication systems, particularly in comparison with the other existing options. This comparison highlights how ES can provide an engine of discovery for understanding human communication. In fact, in complemen...

  20. A review of the evidence regarding associations between attachment theory and experimentally induced pain.

    Science.gov (United States)

    Meredith, Pamela Joy

    2013-04-01

    Theoretical and empirical evidence suggests that adult attachment and pain-related variables are predictably and consistently linked, and that understanding these links may guide pain intervention and prevention efforts. In general, insecure attachment has been portrayed as a risk factor, and secure attachment as a protective factor, for people with chronic pain conditions. In an effort to better understand the relationships among attachment and pain variables, these links have been investigated in pain-free samples using induced-pain techniques. The present paper reviews the available research linking adult attachment and laboratory-induced pain. While the diverse nature of the studies precludes definitive conclusions, together these papers offer support for associations between insecure attachment and a more negative pain experience. The evidence presented in this review highlights areas for further empirical attention, as well as providing some guidance for clinicians who may wish to employ preventive approaches and other interventions informed by attachment theory.

  1. The effects of blocking N/OFQ receptors on orofacial pain following experimental tooth movement in rats.

    Science.gov (United States)

    Shan, Di; He, Yuwei; Long, Hu; Zhou, Yang; Liu, He; Xu, Rui; Huang, Renhuan; Lai, Wenli

    2016-11-01

    The aim of this study was to determine the effects of nociceptin/orphanin FQ peptide receptor (N/OFQ receptor) antagonist on orofacial pain induced by experimental tooth movement in rats. A total of 36 male Sprague-Dawley rats weighing 200-300 g were divided into six groups: a control group, force group, force+saline intraperitoneal group, force+saline periodontal group, force+UFP-101 ([Nphe¹,Arg¹⁴,Lys¹⁵]N/OFQ-NH ₂ antagonist for N/OFQ receptor) intraperitoneal group, and force+UFP-1 01 periodontal group. Closed coil springs were ligated between the upper incisors and first molar to exert an orthodontic force (40 g) between the teeth. Injectable administration dosages were 30 μl saline or 30 μl saline containing 0.03 mg/kg UFP-1 01. Following the injections, orofacial pain levels were assessed through directed face grooming (mouth wiping). Statistical analyses were performed in SPSS 17.0 (Statistical Package for the Social Sciences) and p values less than 0.05 were considered as statistically significant. Orofacial pain levels were significantly higher in the force group than in the control group. Orofacial pain levels differed significantly between the force)group, force+saline periodontal group and force+UFP-101 periodontal group, but were similar between the control group, force+UFP-101 intraperitoneal group and force+saline intraperitoneal group. Moreover, orofacial pain levels did not differ between the force group, force+saline intraperitoneal group and force+UFP-1 01 intraperitoneal group. Periodontal, but not intraperitoneal, administration of UFP-101 could alleviate orofacial pain induced by experimental tooth movement in rats, suggesting that periodontal N/OFQ receptors participate in orofacial pain induced by experimental tooth movement.

  2. The development of human factors experimental evaluation techniques

    Energy Technology Data Exchange (ETDEWEB)

    Sim, Bong Shick; Oh, In Suk; Cha, Kyung Ho; Lee, Hyun Chul; Park, Geun Ok; Cheon, Se Woo; Suh, Sang Moon

    1997-07-01

    New human factors issues, such as evaluation of information navigation, the consideration of operator characteristics, and operator performance assessment, related to the HMI design based on VDUs are being risen. Thus, in order to solve these human factors issues, this project aims to establish the experimental technologies including the techniques for experimental design, experimental measurement, data collection and analysis, and to develop ITF (Integrated Test Facility) suitable for the experiment of HMI design evaluation. For the establish of the experimental data analysis and evaluation methodologies, we developed as the following: (1) a paradigm for human factors experimentation including experimental designs, procedures, and data analysis. (2) the methods for the assessment of operator`s mental workload (3) DAEXESS (data analysis and experiment evaluation supporting system). Also, we have established a experiment execution technologies through the preliminary experiments, such as the suitability evaluation of information display on a LSDP, the evaluation of information display on a LSDP, the evaluation of computerized operation procedure and an experiment of advanced alarm system (ADIOS). Finally, we developed the ITF including human machine simulator, telemetry system, an eye tracking system, an audio/video data measurement system, and three dimensional micro behaviour analysis system. (author). 81 refs., 68 tabs., 73 figs.

  3. Chenopodium ambrosioides L. Reduces Synovial Inflammation and Pain in Experimental Osteoarthritis.

    Directory of Open Access Journals (Sweden)

    Gustavo P Calado

    Full Text Available The chronicity of osteoarthritis (OA, characterized by pain and inflammation in the joints, is linked to a glutamate receptor, N-methyl-D-aspartate (NMDA. The use of plant species such as Chenopodium ambrosioides L. (Amaranthaceae as NMDA antagonists offers a promising perspective. This work aims to analyze the antinociceptive and anti-inflammatory responses of the crude hydroalcoholic extract (HCE of C. ambrosioides leaves in an experimental OA model. Wistar rats were separated into six groups (n = 24: clean (C, negative control (CTL-, positive control (CTL+, HCE0.5, HCE5 and HCE50. The first group received no intervention. The other groups received an intra-articular injection of sodium monoiodoacetate (MIA (8 mg/kg on day 0. After six hours, they were orally treated with saline, Maxicam plus (meloxicam + chondroitin sulfate and HCE at doses of 0.5 mg/kg, 5 mg/kg and 50 mg/kg, respectively. After three, seven and ten days, clinical evaluations were performed (knee diameter, mechanical allodynia, mechanical hyperalgesia and motor activity. On the tenth day, after euthanasia, synovial fluid and draining lymph node were collected for cellular quantification, and cartilage was collected for histopathological analysis. Finally, molecular docking was performed to evaluate the compatibility of ascaridole, a monoterpene found in HCE, with the NMDA receptor. After the third day, HCE reduced knee edema. HCE5 showed less cellular infiltrate in the cartilage and synovium and lower intensities of allodynia from the third day and of hyperalgesia from the seventh day up to the last treatment day. The HCE5 and HCE50 groups improved in forced walking. In relation to molecular docking, ascaridole showed NMDA receptor binding affinity. C. ambrosioides HCE was effective in the treatment of OA because it reduced synovial inflammation and behavioral changes due to pain. This effect may be related to the antagonistic effect of ascaridole on the NMDA receptor.

  4. Experimental muscle pain produces central modulation of proprioceptive signals arising from jaw muscle spindles.

    Science.gov (United States)

    Capra, N F; Ro, J Y

    2000-05-01

    The aim of the present study was to investigate the effects of intramuscular injection with hypertonic saline, a well-established experimental model for muscle pain, on central processing of proprioceptive input from jaw muscle spindle afferents. Fifty-seven cells were recorded from the medial edge of the subnucleus interpolaris (Vi) and the adjacent parvicellular reticular formation from 11 adult cats. These cells were characterized as central units receiving jaw muscle spindle input based on their responses to electrical stimulation of the masseter nerve, muscle palpation and jaw stretch. Forty-five cells, which were successfully tested with 5% hypertonic saline, were categorized as either dynamic-static (DS) (n=25) or static (S) (n=20) neurons based on their responses to different speeds and amplitudes of jaw movement. Seventy-six percent of the cells tested with an ipsilateral injection of hypertonic saline showed a significant modulation of mean firing rates (MFRs) during opening and/or holding phases. The most remarkable saline-induced change was a significant reduction of MFR during the hold phase in S units (100%, 18/18 modulated). Sixty-nine percent of the DS units (11/16 modulated) also showed significant changes in MFRs limited to the hold phase. However, in the DS neurons, the MFRs increased in seven units and decreased in four units. Finally, five DS neurons showed significant changes of MFRs during both opening and holding phases. Injections of isotonic saline into the ipsilateral masseter muscle had little effect, but hypertonic saline injections made into the contralateral masseter muscle produced similar results to ipsilateral injections with hypertonic saline. These results unequivocally demonstrate that intramuscular injection with an algesic substance, sufficient to produce muscle pain, produces significant changes in the proprioceptive properties of the jaw movement-related neurons. Potential mechanisms involved in saline-induced changes in the

  5. Nursing students' assessment of pain and decision of triage for different ethnic groups: An experimental study.

    Science.gov (United States)

    Chan, Joanne C Y; Hamamura, Takeshi

    2015-08-01

    Pain management is a priority in nursing care but little is known about the factors that affect nursing students' assessment of pain expressed by patients of different ethnic backgrounds. This study examined undergraduate nursing students' assessment of pain and decision of triage when pain was expressed in different languages and their relation to students' empathy and social identity. Comparison between students with and without clinical experience was also carried out. This is a cross-sectional quantitative design. This study took place at a university in Hong Kong. 74 female undergraduate nursing students. Students listened to eight audio recordings in which an individual expressed pain in one of the two dialects of Chinese, either Cantonese or Putonghua. For each dialect, two recordings depicted mild pain and two depicted severe pain. After listening to each recording, students rated the pain level and indicated their decision of triage. Subsequently, students completed a questionnaire that measured their empathy and social identity and reported their demographics. The data were analyzed by descriptive statistics, correlational analyses, and t-tests. Severe pain described in Putonghua was rated as more intense than that described in Cantonese but it was not classified as more urgent. Students with clinical experience tended to perceive mild pain as less painful and less urgent than those without clinical experience. For mild pain described in Cantonese, students with clinical experience evaluated it as more urgent than those without such experience. The empathy level of students with and without clinical experience was comparable. Students with more empathy, especially those without clinical experience, reported heightened perceived intensity of severe pain described in Putonghua. Nurse educators should note that empathy, social identity, and clinical experience may alter students' pain assessment of patients from different ethnicities. Pain education needs to

  6. Experimental allergic encephalomyelitis: peculiarities of pain-relieving therapy and place of anticonvulsants as analgetics

    Directory of Open Access Journals (Sweden)

    Nefyodov O.O.

    2015-11-01

    Full Text Available Multiple sclerosis (MS is the most common demyelinating disease affecting mainly young people of the working age (16-45 years and quickly leading to disability. Available data constitute that up to 80% of MS patients suffer from pain at different disease periods. Pain management and the analgesic drug choice in MS patients may be difficult. Anticonvulsant drugs possess an analgesic activity and are widely used in patients presenting painful neuropathic symptoms. Based on that, we aimed to investigate the nociceptive potential changes as well as the research-oriented behavior using the "open field" test in rat. An experimental animal equivalent of multiple sclerosis has been modeled, based on the methylprednisolone (M administration. Animals were also administered anticonvulsants (carbamazepine, topiramate, sodium volproat, pregabalin and gabapentin. The stu­dy showed advantages of gabapentin and pregabalin use in simulated disease treatment. This statement is based on the "open field" test results, where the motor-oriented rats’ behavior was evaluated. Administration of M+gabapentin and M+pregabalin showed positive dynamics of the motor activity: the number of squares crossed increased by 80.86% (p<0.05 and 81.73% (р<0.05 respectively. Maximum recovery of the research activity (peeking in "mink" was re­gis­tered in animals administered M+pregabalin: the increase rate was 300% (r<0.05 comparing with the 12th day of ex­periment. It was shown, that 5-days administration of M+gabapentin and M+pregabalin caused muscle tone impro­ve­ment by 190% (p<0.05 and 200% (p<0.05 respectively, comparing with animals with untreated multiple sclerosis. A sig­ni­fi­cant increase of analgesic activity of M+pregabalin and M+gabapentin combinations used together with me­thyl­pred­nisolone by 4.1 (p<0.05 and 3.6 (p<0.05 times was registered comparing with the initial methylprednisolone background.

  7. Asymmetric dimethylarginine may mediate increased heat pain threshold in experimental chronic kidney disease.

    Science.gov (United States)

    Kielstein, Jan T; Suntharalingam, Mayuren; Perthel, Ronny; Rong, Song; Martens-Lobenhoffer, Jens; Jäger, Kristin; Bode-Böger, Stefanie M; Nave, Heike

    2012-03-01

    Thermal sensitivity in uraemia is decreased. Non-selective synthetic nitric oxide synthase (NOS) inhibitors significantly attenuate thermal hyperalgesia in preclinical models. The aim of our study was to evaluate the effect of experimental uraemia, which is associated with an increase of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA), on thermal sensitivity in rats. Furthermore, we intended to study the effect of chronic ADMA infusion alone on thermal sensitivity. Male Sprague-Dawley rats (n = 54), 10 weeks old, weight 370-430 g, were randomly assigned to three groups receiving either (i) isotonic saline or (ii) ADMA via osmotic mini pumps or (iii) underwent 5/6 nephrectomy (Nx). After 14 days, 50% of all animals from all groups underwent thermal sensitivity testing and terminal blood draw. After 28 days, the remaining animals underwent the same procedures. Thermal sensitivity examination was performed by the hot-plate test, measuring time from heat exposition to first paw licking or jumping of the animal. While the median [interquartile range] latency time between heat exposition to first paw licking or jumping of the animal in the NaCl infusion group remained unchanged between Day 14 (8.4 [6.75-11.50] s) and Day 28 (7.35 [6.10-7.90] s) both, ADMA infusion and 5/6 nephrectomy tended to increase the thermal pain threshold at Day 14 (9.25 [6.55-12.18] s) and (9.50 [5.8 ± 11.0] s), respectively, compared to NaCl on Day 14 (8.4 [6.75-11.50] s). This difference became statistical significant at Day 28 where the median latency time in the ADMA group (13.10 [11.85-15.95] s) and in the 5/6 Nx group (13.50 [10.85-17.55] s) were significantly higher than in the NaCl group (7.35 [6.10-7.90] s). Induction of progressive renal failure in rats by 5/6 nephrectomy, which is accompanied by a marked increase of the serum levels of the endogenous NOS inhibitor ADMA, leads to a significantly increased heat pain threshold at 28 days. The sole infusion of ADMA into

  8. Effects of experimental muscle pain on shoulder-abduction force steadiness and muscle activity in healthy subjects

    DEFF Research Database (Denmark)

    Bandholm, Thomas Quaade; Rasmussen, Lars; Aagaard, Per

    2007-01-01

    We previously demonstrated that the steadiness of shoulder abduction is reduced in patients with subacromial impingement syndrome (SIS), which might be related to shoulder pain associated with the SIS. The aim of the present study was to examine the acute effects of experimental shoulder muscle p...

  9. Effect of experimental stress in 2 different pain conditions affecting the facial muscles.

    Science.gov (United States)

    Woda, Alain; L'heveder, Gildas; Ouchchane, Lemlih; Bodéré, Céline

    2013-05-01

    Chronic facial muscle pain is a common feature in both fibromyalgia (FM) and myofascial (MF) pain conditions. In this controlled study, a possible difference in the mode of deregulation of the physiological response to a stressing stimulus was explored by applying an acute mental stress to FM and MF patients and to controls. The effects of the stress test were observed on pain, sympathetic variables, and both tonic and reflex electromyographic activities of masseteric and temporal muscles. The statistical analyses were performed through a generalized linear model including mixed effects. Painful reaction to the stressor was stronger (P < .001) and longer (P = .011) in FM than in MF independently of a higher pain level at baseline. The stress-induced autonomic changes only seen in FM patients did not reach significance. The electromyographic responses to the stress test were strongest for controls and weakest for FM. The stress test had no effect on reflex activity (area under the curve [AUC]) or latency, although AUC was high in FM and latencies were low in both pain groups. It is suggested that FM is characterized by a lower ability to adapt to acute stress than MF. This study showed that an acute psychosocial stress triggered several changes in 2 pain conditions including an increase in pain of larger amplitude in FM than in MF pain. Similar stress-induced changes should be explored as possible mechanisms for differentiation between dysfunctional pain conditions. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

  10. Determining the Neural Substrate for Encoding a Memory of Human Pain and the Influence of Anxiety.

    Science.gov (United States)

    Tseng, Ming-Tsung; Kong, Yazhuo; Eippert, Falk; Tracey, Irene

    2017-12-06

    To convert a painful stimulus into a briefly maintainable construct when the painful stimulus is no longer accessible is essential to guide human behavior and avoid dangerous situations. Because of the aversive nature of pain, this encoding process might be influenced by emotional aspects and could thus vary across individuals, but we have yet to understand both the basic underlying neural mechanisms as well as potential interindividual differences. Using fMRI in combination with a delayed-discrimination task in healthy volunteers of both sexes, we discovered that brain regions involved in this working memory encoding process were dissociable according to whether the to-be-remembered stimulus was painful or not, with the medial thalamus and the rostral anterior cingulate cortex encoding painful and the primary somatosensory cortex encoding nonpainful stimuli. Encoding of painful stimuli furthermore significantly enhanced functional connectivity between the thalamus and medial prefrontal cortex (mPFC). With regards to emotional aspects influencing encoding processes, we observed that more anxious participants showed significant performance advantages when encoding painful stimuli. Importantly, only during the encoding of pain, the interindividual differences in anxiety were associated with the strength of coupling between medial thalamus and mPFC, which was furthermore related to activity in the amygdala. These results indicate not only that there is a distinct signature for the encoding of a painful experience in humans, but also that this encoding process involves a strong affective component. SIGNIFICANCE STATEMENT To convert the sensation of pain into a briefly maintainable construct is essential to guide human behavior and avoid dangerous situations. Although this working memory encoding process is implicitly contained in the majority of studies, the underlying neural mechanisms remain unclear. Using fMRI in a delayed-discrimination task, we found that the

  11. A preliminary report on stem cell therapy for neuropathic pain in humans

    Directory of Open Access Journals (Sweden)

    Vickers ER

    2014-05-01

    Full Text Available E Russell Vickers,1 Elisabeth Karsten,2 John Flood,3 Richard Lilischkis21Sydney Oral and Maxillofacial Surgery, NSW, Australia; 2Regeneus Ltd, Gordon, NSW, Australia; 3St Vincents Hospital, Sydney, NSW, AustraliaObjective: Mesenchymal stem cells (MSCs have been shown in animal models to attenuate chronic neuropathic pain. This preliminary study investigated if: i injections of autologous MSCs can reduce human neuropathic pain and ii evaluate the safety of the procedure.Methods: Ten subjects with symptoms of neuropathic trigeminal pain underwent liposuction. The lipoaspirate was digested with collagenase and washed with saline three times. Following centrifugation, the stromal vascular fraction was resuspended in saline, and then transferred to syringes for local injections into the pain fields. Outcome measures at 6 months assessed reduction in: i pain intensity measured by standard numerical rating scale from 0–10 and ii daily dosage requirements of antineuropathic pain medication.Results: Subjects were all female (mean age 55.3 years ± standard deviation [SD] 14.67; range 27–80 years with pain symptoms lasting from 4 months to 6 years and 5 months. Lipoaspirate collection ranged from 102–214 g with total cell numbers injected from 33 million to 162 million cells. Cell viability was 62%–91%. There were no systemic or local tissue side effects from the stem cell therapy (n=41 oral and facial injection sites. Clinical pain outcomes showed that at 6 months, 5/9 subjects had reduced both pain intensity scores and use of antineuropathic medication. The mean pain score pre-treatment was 7.5 (SD 1.58 and at 6 months had decreased to 4.3 (SD 3.28, P=0.018, Wilcoxon signed-rank test. Antineuropathic pain medication use showed 5/9 subjects reduced their need for medication (gabapentin, P=0.053, Student's t-test.Conclusion: This preliminary open-labeled study showed autologous administration of stem cells for neuropathic trigeminal pain

  12. Brain Network Response to Acupuncture Stimuli in Experimental Acute Low Back Pain: An fMRI Study

    Directory of Open Access Journals (Sweden)

    Yu Shi

    2015-01-01

    Full Text Available Most neuroimaging studies have demonstrated that acupuncture can significantly modulate brain activation patterns in healthy subjects, while only a few studies have examined clinical pain. In the current study, we combined an experimental acute low back pain (ALBP model and functional magnetic resonance imaging (fMRI to explore the neural mechanisms of acupuncture analgesia. All ALBP subjects first underwent two resting state fMRI scans at baseline and during a painful episode and then underwent two additional fMRI scans, once during acupuncture stimulation (ACUP and once during tactile stimulation (SHAM pseudorandomly, at the BL40 acupoint. Our results showed that, compared with the baseline, the pain state had higher regional homogeneity (ReHo values in the pain matrix, limbic system, and default mode network (DMN and lower ReHo values in frontal gyrus and temporal gyrus; compared with the OFF status, ACUP yielded broad deactivation in subjects, including nearly all of the limbic system, pain status, and DMN, and also evoked numerous activations in the attentional and somatosensory systems; compared with SHAM, we found that ACUP induced more deactivations and fewer activations in the subjects. Multiple brain networks play crucial roles in acupuncture analgesia, suggesting that ACUP exceeds a somatosensory-guided mind-body therapy for ALBP.

  13. Pain Experience is Somatotopically Organized and Overlaps with Pain Anticipation in the Human Cerebellum.

    Science.gov (United States)

    Michelle Welman, F H S; Smit, Albertine E; Jongen, Joost L M; Tibboel, Dick; van der Geest, Jos N; Holstege, Jan C

    2018-02-26

    Many fMRI studies have shown activity in the cerebellum after peripheral nociceptive stimulation. We investigated whether the areas in the cerebellum that were activated after nociceptive thumb stimulation were separate from those after nociceptive toe stimulation. In an additional experiment, we investigated the same for the anticipation of a nociceptive stimulation on the thumb or toe. For his purpose, we used fMRI after an electrical stimulation of the thumb and toe in 19 adult healthy volunteers. Following nociceptive stimulation, different areas were activated by stimulation on the thumb (lobule VI ipsilaterally and Crus II mainly contralaterally) and toe (lobules VIII-IX and IV-V bilaterally and lobule VI contralaterally), i.e., were somatotopically organized. Cerebellar areas innervated non-somatotopically by both toe and thumb stimulation were the posterior vermis and Crus I, bilaterally. In the anticipation experiment, similar results were found. However, here, the somatotopically activated areas were relatively small for thumb and negligible for toe stimulation, while the largest area was innervated non-somatotopically and consisted mainly of Crus I and lobule VI bilaterally. These findings indicate that nociceptive stimulation and anticipation of nociceptive stimulation are at least partly processed by the same areas in the cerebellum. This was confirmed by an additional conjunction analysis. Based on our findings, we hypothesize that input that is organized in a somatotopical manner reflects direct input from the spinal cord, while non-somatotopically activated parts of the cerebellum receive their information indirectly through cortical and subcortical connections, possibly involved in processing contextual emotional states, like the expectation of pain.

  14. The Animal Model of Spinal Cord Injury as an Experimental Pain Model

    OpenAIRE

    Nakae, Aya; Nakai, Kunihiro; Yano, Kenji; Hosokawa, Ko; Shibata, Masahiko; Mashimo, Takashi

    2011-01-01

    Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of patholo...

  15. Effect of Experimental Hand Pain on Training-Induced Changes in Motor Performance and Corticospinal Excitability

    Directory of Open Access Journals (Sweden)

    Nicolas Mavromatis

    2017-02-01

    Full Text Available Pain influences plasticity within the sensorimotor system and the aim of this study was to assess the effect of pain on changes in motor performance and corticospinal excitability during training for a novel motor task. A total of 30 subjects were allocated to one of two groups (Pain, NoPain and performed ten training blocks of a visually-guided isometric pinch task. Each block consisted of 15 force sequences, and subjects modulated the force applied to a transducer in order to reach one of five target forces. Pain was induced by applying capsaicin cream to the thumb. Motor performance was assessed by a skill index that measured shifts in the speed–accuracy trade-off function. Neurophysiological measures were taken from the first dorsal interosseous using transcranial magnetic stimulation. Overall, the Pain group performed better throughout the training (p = 0.03, but both groups showed similar improvements across training blocks (p < 0.001, and there was no significant interaction. Corticospinal excitability in the NoPain group increased halfway through the training, but this was not observed in the Pain group (Time × Group interaction; p = 0.01. These results suggest that, even when pain does not negatively impact on the acquisition of a novel motor task, it can affect training-related changes in corticospinal excitability.

  16. Pain sensation and nociceptive reflex excitability in surgical patients and human volunteers

    DEFF Research Database (Denmark)

    Dahl, J B; Erichsen, C J; Fuglsang-Frederiksen, A

    1992-01-01

    Pain threshold, nociceptive flexion reflex (NFR) threshold and responses to suprathreshold stimulation were investigated in 15 female patients (mean age 32 yr (range 22-48 yr)) before and 68 (range 48-96) h after gynaecological laparotomy. Control measurements were performed in 17 healthy human v...

  17. Comparative Analysis of Pain Behaviours in Humanized Mouse Models of Sickle Cell Anemia.

    Directory of Open Access Journals (Sweden)

    Jianxun Lei

    Full Text Available Pain is a hallmark feature of sickle cell anemia (SCA but management of chronic as well as acute pain remains a major challenge. Mouse models of SCA are essential to examine the mechanisms of pain and develop novel therapeutics. To facilitate this effort, we compared humanized homozygous BERK and Townes sickle mice for the effect of gender and age on pain behaviors. Similar to previously characterized BERK sickle mice, Townes sickle mice show more mechanical, thermal, and deep tissue hyperalgesia with increasing age. Female Townes sickle mice demonstrate more hyperalgesia compared to males similar to that reported for BERK mice and patients with SCA. Mechanical, thermal and deep tissue hyperalgesia increased further after hypoxia/reoxygenation (H/R treatment in Townes sickle mice. Together, these data show BERK sickle mice exhibit a significantly greater degree of hyperalgesia for all behavioral measures as compared to gender- and age-matched Townes sickle mice. However, the genetically distinct "knock-in" strategy of human α and β transgene insertion in Townes mice as compared to BERK mice, may provide relative advantage for further genetic manipulations to examine specific mechanisms of pain.

  18. Effect of gender and hand laterality on pain processing in human neonates.

    Science.gov (United States)

    Ozawa, Mio; Kanda, Katsuya; Hirata, Michio; Kusakawa, Isao; Suzuki, Chieko

    2011-01-01

    Previous studies in adults have reported that handedness and gender can affect pain perception. However, it is currently unclear when these differences emerge in human development. Therefore, we examined prefrontal responses to pain stimulation among newborns during their first acute pain experience after birth. Forty newborns at 4-6 days postnatal age were observed during clinically required blood sampling while prefrontal activation was measured with near infrared spectroscopy. Blood sampling in this study was the first experience of a procedure involving skin breaking for these infants. We divided subjects into a right-hand stimulation group (n=21) and a left-hand stimulation group (n=19), depending on whether blood was sampled from the right or the left hand. A three-way analysis of variance (ANOVA) was conducted to examine the effects of several variables on the magnitude of the oxy-Hb value in response to pain stimulus, including stimulus side (right hand or left hand), gender (male or female), recording side (right prefrontal area or left prefrontal area) and interactions between these variables. The data revealed a significant effect of stimulus side (F (1, 72)=9.892, P=0.002), showing that the right-hand stimulation induced a greater prefrontal activation than the left-hand stimulation. No significant gender difference or interactions were found. Our findings suggest that hand laterality affects pain perception even in neonates. However, gender differences in pain perception did not appear to occur during the neonatal period. Further investigations using brain-imaging techniques are required to identify laterality- or gender-related differences in pain processing in humans. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  19. The role of executive functioning in children's attentional pain control: an experimental analysis.

    Science.gov (United States)

    Verhoeven, Katrien; Dick, Bruce; Eccleston, Christopher; Goubert, Liesbet; Crombez, Geert

    2014-02-01

    Directing attention away from pain is often used in children's pain treatment programs to control pain. However, empirical evidence concerning its effectiveness is inconclusive. We therefore sought to understand other influencing factors, including executive function and its role in the pain experience. This study investigates the role of executive functioning in the effectiveness of distraction. School children (n=164) completed executive functioning tasks (inhibition, switching, and working memory) and performed a cold-pressor task. One half of the children simultaneously performed a distracting tone-detection task; the other half did not. Results showed that participants in the distraction group were engaged in the distraction task and were reported to pay significantly less attention to pain than controls. Executive functioning influenced distraction task engagement. More specifically, participants with good inhibition and working memory abilities performed the distraction task better; participants with good switching abilities reported having paid more attention to the distraction task. Furthermore, distraction was found to be ineffective in reducing pain intensity and affect. Executive functioning did not influence the effectiveness of distraction. However, a relationship was found between executive functioning and pain affect, indicating that participants with good inhibition and working memory abilities experienced the cold-pressor task as less stressful and unpleasant. Our findings suggest that distraction as a process for managing pain is complex. While it appears that executive function may play a role in adult distraction, in this study it did not direct attention away from pain. It may instead be involved in the overall pain experience. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  20. Dehydration enhances pain-evoked activation in the human brain compared with rehydration.

    Science.gov (United States)

    Ogino, Yuichi; Kakeda, Takahiro; Nakamura, Koji; Saito, Shigeru

    2014-06-01

    Negative effects of dehydration on the human brain and cognitive function have been reported. In this study, we examined the effects of dehydration on pain thresholds and cortical activations in response to pain, compared with rehydration with an oral rehydration solution (ORS) by functional magnetic resonance imaging. Five healthy adult men were subjected to dehydration and rehydration on 2 different days. The condition on the first day was randomly assigned to each subject. They completed a 40-minute exercise protocol using a walking machine after 12 hours of fasting under both conditions. For rehydration, the subjects consumed up to 3000 mL ORS starting from the night before the test day. After exercise, a painful stimulus (cold pressor test) was applied to the subjects' medial forearm in a magnetic resonance imaging scanning gantry, and pain-evoked brain activation was analyzed. On the rehydration day, each of the subjects consumed an average of 2040 mL (range; 1800-2500 mL) ORS. Physiological data revealed that subjects when dehydrated lost more weight from exercise than subjects when rehydrated had a larger heart rate increase, a higher tympanic temperature, and a higher urine osmolality. Subjective data revealed that the subjects reported significantly stronger thirst while dehydrated than while rehydrated with ORS, although the levels of hunger and anxiety and mood did not significantly differ between conditions. The cold pressor test robustly activated the pain-related neural network, notably the anterior cingulate cortex, insula, and thalamus. Such activations in the dehydrated subjects were greater than those in the rehydrated subjects in terms of peak and cluster, accompanied by a decrease in pain threshold (P = 0.001). Our findings suggest that dehydration brings about increased brain activity related to painful stimuli together with enhanced thirst, whereas rehydration with ORS alleviates thirst and decreases brain activity related to painful stimuli.

  1. Uterus transplantation: Experimental animal models and recent experience in humans

    Directory of Open Access Journals (Sweden)

    Sadık Şahin

    2015-03-01

    Full Text Available Uterus transplantation has been considered as an alternative management modality in the last few years for adoption or gestational surrogacy for women with absence of uterus due to congenital or acquired reasons. Surrogacy is legal in only a few countries because of ethical, social and legal issues. Up to date, a total of 11 uterus transplantation cases have been reported in which uteri were harvested from ten live donors and one donor with brain death. After unsuccessful attempt of first uterus transplantation, many studies have been conducted in animals and these experimental models enabled our knowledge to increase on this topic. First experimental studies were performed in rodents; later uterus transplantation was accomplished in sheep, pigs and rabbits. Recently, researches in non-human primates have led the experience regarding transplantation technique and success to improve. In this review, we reviewed the experimental animal researches in the area of uterus transplantation and recent experience in humans.

  2. Gait changes in patients with knee osteoarthritis are replicated by experimental knee pain

    DEFF Research Database (Denmark)

    Henriksen, Marius; Graven-Nielsen, Thomas; Aaboe, Jens

    2010-01-01

    Medial knee osteoarthritis (OA) is characterized by pain and associated with abnormal knee moments during walking. The relationship between knee OA pain and gait changes remains to be clarified, and a better understanding of this link could advance the treatment and prevention of disease...

  3. Autonomic nervous system function in patients with functional abdominal pain. An experimental study

    DEFF Research Database (Denmark)

    Jørgensen, L S; Christiansen, P; Raundahl, U

    1993-01-01

    Functional abdominal pain--that is, pain without demonstrable organic abnormalities--has often been associated with psychologic stress. The aim of the present study was to investigate whether sympathetic nervous system response to laboratory stress and basal parasympathetic neural activity were...

  4. Muscular heat and mechanical pain sensitivity after lengthening contractions in humans and animals.

    Science.gov (United States)

    Queme, Fernando; Taguchi, Toru; Mizumura, Kazue; Graven-Nielsen, Thomas

    2013-11-01

    Mechanical sensitivity of muscle nociceptors was previously shown to increase 2 days after lengthening contractions (LC), but heat sensitivity was not different despite nerve growth factor (NGF) being upregulated in the muscle during delayed-onset muscle soreness (DOMS). The discrepancy of these results and lack of other reports drove us to assess heat sensitivity during DOMS in humans and to evaluate the effect of NGF on the heat response of muscle C-fibers. Pressure pain thresholds and pain intensity scores to intramuscular injection of isotonic saline at 48°C and capsaicin were recorded in humans after inducing DOMS. The response of single unmyelinated afferents to mechanical and heat stimulations applied to their receptive field was recorded from muscle-nerve preparations in vitro. In humans, pressure pain thresholds were reduced but heat and capsaicin pain responses were not increased during DOMS. In rats, the mechanical but not the heat sensitivity of muscle C-fibers was increased in the LC group. NGF applied to the receptive field facilitated the heat sensitivity relative to the control. The absence of facilitated heat sensitivity after LC, despite the NGF sensitization, may be explained if the NGF concentration produced after LC is not sufficient to sensitize nociceptor response to heat. This article presents new findings on the basic mechanisms underlying hyperalgesia during DOMS, which is a useful model to study myofascial pain syndrome, and the role of NGF on muscular nociception. This might be useful in the search for new pharmacologic targets and therapeutic approaches. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

  5. The human factors and the safety of experimentation reactors

    International Nuclear Information System (INIS)

    Jeffroy, F.; Delaporte-Normier, M.L.

    2007-01-01

    Inside IRSN (Institute for Radiological protection and Nuclear Safety), the mission of the Human Factors Group is to assess the way operators of nuclear installations take into account the risks related to human activities. In the last few years, IRSN has been involved in the safety analysis of different installations where Cea develops research programs, in particular experimental reactors. The first part of this article presents the methodology used by IRSN to evaluate how operators take into account risks related to human activities. This methodology is made up of 4 steps: 1) the identification of the human activities that convey a risk for the installation nuclear safety (safety-sensitive activities), for instance in the case of the Masurca reactor, it has been shown that errors made during the manufacturing of fuel tubes can lead to a criticality accident; 2) listing all the dispositions or arrangements taken to make human safety-sensitive activities more reliable; 3) checking the efficiency of such dispositions or arrangements; and 4) assessing the ability of the operators to generate the adequate dispositions or arrangements. The second part highlights the necessity to develop inside these research installations an organisation that facilitates cooperation between experimenters and operators

  6. Efficacy and safety of PPC-5650 on experimental rectal pain in patients with irritable bowel syndrome

    DEFF Research Database (Denmark)

    Nielsen, Lecia Møller; Olesen, Anne Estrup; Andresen, Trine

    2015-01-01

    PPC-5650 is a new pharmacological agent that can modulate acid-sensing ion channel activity, leading to a reduction in the pain signal under up-regulated conditions. The non-clinical programme for PPC-5650 supported a role for this novel agent in the treatment of pain in patients with irritable...... bowel syndrome (IBS). In patients with IBS, the aims of the study were: (1) to assess the efficacy of a single bolus of PPC-5650 locally applied in the rectum using multi-modal stimulations of the recto sigmoid and (2) to assess the safety profile of PPC-5650. The study was a randomized, double......-blind, placebo-controlled, cross-over trial in patients with IBS, excluding females of child-bearing potential. The study consisted of a training visit, study visit 1 and 2 and a follow-up visit. Rectosigmoid electrical, thermal and mechanical stimulations were performed, pain perception was rated on a pain...

  7. Effects of target-controlled infusion of high-dose naloxone on pain and hyperalgesia in a human thermal injury model

    DEFF Research Database (Denmark)

    Springborg, Anders D; Jensen, Elisabeth K; Taylor, Bradley K

    2016-01-01

    /kg, 4 mg/mL) or placebo (normal saline) intravenous. The primary outcome was SHA assessed by weighted-pin instrument (128 mN) 0, 1, 2, and 165 to 169 hours after the thermal injury (day 1-4). The secondary outcomes were pin-prick pain thresholds assessed by weighted-pin instrument (8-512 mN) at primary......Mu-opioid-receptor antagonists have been extensively studied in experimental research as pharmacological tools uncovering mechanisms of pain modulation by the endogenous opioid system. In rodents, administration of high doses of mu-opioid-receptor antagonists after the resolution of an inflammatory...... injury has demonstrated reinstatement of nociceptive hypersensitivity indicating unmasking of latent sensitization. In a recent human study, pain hypersensitivity assessed as secondary hyperalgesia area (SHA), was reinstated 7 days after a mild thermal injury, in 4 out of 12 subjects after a naloxone...

  8. Cardiac complication after experimental human malaria infection: a case report

    Directory of Open Access Journals (Sweden)

    Druilhe Pierre

    2009-12-01

    Full Text Available Abstract A 20 year-old healthy female volunteer participated in a clinical Phase I and IIa safety and efficacy trial with candidate malaria vaccine PfLSA-3-rec adjuvanted with aluminium hydroxide. Eleven weeks after the third and last immunization she was experimentally infected by bites of Plasmodium falciparum-infected mosquitoes. When the thick blood smear became positive, at day 11, she was treated with artemether/lumefantrine according to protocol. On day 16 post-infection i.e. two days after completion of treatment, she woke up with retrosternal chest pain. She was diagnosed as acute coronary syndrome and treated accordingly. She recovered quickly and her follow-up was uneventful. Whether the event was related to the study procedures such as the preceding vaccinations, malaria infection or antimalarial drugs remains elusive. However, the relation in time with the experimental malaria infection and apparent absence of an underlying condition makes the infection the most probable trigger. This is in striking contrast, however, with the millions of malaria cases each year and the fact that such complication has never been reported in the literature. The rare occurrence of cardiac events with any of the preceding study procedures may even support a coincidental finding. Apart from acute coronary syndrome, myocarditis can be considered as a final diagnosis, but the true nature and patho-physiological explanation of the event remain unclear.

  9. Hypnosis and Local Anesthesia for Dental Pain Relief-Alternative or Adjunct Therapy?-A Randomized, Clinical-Experimental Crossover Study.

    Science.gov (United States)

    Wolf, Thomas Gerhard; Wolf, Dominik; Callaway, Angelika; Below, Dagna; d'Hoedt, Bernd; Willershausen, Brita; Daubländer, Monika

    2016-01-01

    This prospective randomized clinical crossover trial was designed to compare hypnosis and local anesthesia for experimental dental pain relief. Pain thresholds of the dental pulp were determined. A targeted standardized pain stimulus was applied and rated on the Visual Analogue Scale (0-10). The pain threshold was lower under hypnosis (58.3 ± 17.3, p local anesthesia. The pain stimulus was scored higher under hypnosis (3.9 ± 3.8) than with local anesthesia (0.0, p Local anesthesia was superior to hypnosis and is a safe and effective method for pain relief in dentistry. Hypnosis seems to produce similar effects observed under sedation. It can be used in addition to local anesthesia and in individual cases as an alternative for pain control in dentistry.

  10. Tanezumab: a selective humanized mAb for chronic lower back pain

    Directory of Open Access Journals (Sweden)

    Webb MP

    2018-02-01

    Full Text Available Michael P Webb,1 Erik M Helander,2 Bethany L Menard,2 Richard D Urman,3 Alan D Kaye2 1Department of Anesthesiology, North Shore Hospital, Auckland, New Zealand; 2Department of Anesthesiology, LSU School of Medicine, New Orleans, LA, USA; 3Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Abstract: Chronic lower back pain is a significant disease that affects nearly 20% of the worldwide population. Along with hindering patients’ quality of life, chronic lower back pain is considered to be the second most common cause of disability among Americans. Treating chronic lower back pain is often a challenge for providers, especially in light of our current opioid epidemic. With this epidemic and an increased aging population, there is an imminent need for development of new pharmacologic therapeutic options, which are not only effective but also pose minimal adverse effects to the patient. With these considerations, a novel therapeutic agent called tanezumab has been developed and studied. Tanezumab is a humanized monoclonal immunoglobulin G2 antibody that works by inhibiting the binding of NGF to its receptors. NGF is involved in the function of sensory neurons and fibers involved in nociceptive transduction. It is commonly seen in excess in inflammatory joint conditions and in chronic pain patients. Nociceptors are dependent on NGF for growth and ongoing function. The inhibition of NGF binding to its receptors is a mechanism by which pain pathways can be interrupted. In this article, a number of recent randomized controlled trials are examined relating to the efficacy and safety of tanezumab in the treatment of chronic lower back pain. Although tanezumab was shown to be an effective pain modulator in major trials, several adverse effects were seen among different doses of the medication, one of which led to a clinical hold placed by the US Food and Drug

  11. Effects of perceived and exerted pain control on neural activity during pain relief in experimental heat hyperalgesia: a fMRI study.

    Science.gov (United States)

    Mohr, C; Leyendecker, S; Petersen, D; Helmchen, C

    2012-04-01

    Perceived control over pain can attenuate pain perception by mechanisms of endogenous pain control and emotional reappraisal irrespective of whether this control is exerted or only perceived. Self-initiated termination of pain elicits different expectations of subsequent pain relief as compared to perceived pain control. It is unknown whether and how this perceived vs. exerted control on pain differs and affects subsequent pain relief. Using fMRI, we studied two factors of pain control on pain relief: the (i) sense of control (perceived control but no execution) and (ii) the execution of control (exerted control). To account for the impact of factual execution of pain control on pain relief we applied bearable short and hardly bearable long contact-heat stimuli which were applied either controllable or not. Using controllability as factor, there was dissociable neural activity during pain relief: following the perceived control condition neural activity was found in the orbitofrontal and mediofrontal cortex and, following the exerted control condition, in the anterolateral and dorsolateral prefrontal cortex and posterior parietal cortex. We conclude that (i) pain controllability has an impact on pain relief and (ii) the prefrontal cortex shows dissociable neural activity during pain relief following exerted vs. perceived pain control. This might reflect the higher grade of uncertainty during pain relief following perceived pain control mediated by the orbitofrontal and medial prefrontal cortex and processes of working memory and updating expectations during pain relief following exerted control mediated by the lateral prefrontal cortex. © 2011 European Federation of International Association for the Study of Pain Chapters.

  12. Experimental Human Cell and Tissue Models of Pemphigus

    Science.gov (United States)

    van der Wier, Gerda; Pas, Hendri H.; Jonkman, Marcel F.

    2010-01-01

    Pemphigus is a chronic mucocutaneous autoimmune bullous disease that is characterized by loss of cell-cell contact in skin and/or mucous membranes. Past research has successfully identified desmosomes as immunological targets and has demonstrated that acantholysis is initiated through direct binding of IgG. The exact mechanisms of acantholysis, however, are still missing. Experimental model systems have contributed considerably to today's knowledge and are still a favourite tool of research. In this paper we will describe to what extent human cell and tissue models represent the in vivo situation, for example, organ cultures of human skin, keratinocyte cultures, and human skin grafted on mice and, furthermore, how suitable they are to study the pathogenesis of pemphigus. Organ cultures closely mimic the architecture of the epidermis but are less suitable to answer posed biochemical questions. Cultured keratinocyte monolayers are convenient in this respect, but their desmosomal make-up in terms of adhesion molecules does not exactly reflect the in vivo situation. Reconstituted skin is a relatively new model that approaches organ culture. In models of human skin grafted on mice, acantholysis can be studied in actual human skin but now with all the advantages of an animal model. PMID:20585596

  13. Role of capsaicin- and heat-sensitive afferents in stimulation of acupoint-induced pain and analgesia in humans.

    Science.gov (United States)

    Lei, Jing; Ye, Gang; Wu, Jiang-Tao; Pertovaara, Antti; You, Hao-Jun

    2017-09-01

    We investigated role of capsaicin-sensitive afferents within and without the areas of Zusanli (ST36)/Shangjuxu (ST37) acupoints along the stomach (ST) meridian in the perception and modulation of pain assessed by visual analog scale of pain and its distribution rated by subjects, pressure pain threshold (PPT), and heat pain threshold (HPT) in humans. Compared with the treatment of non-acupoint area, capsaicin (100µg/50µl) administered into either ST36 or ST37 acupoint caused the strongest pain intensity and the most extensive pain distribution, followed by rapid onset, bilateral, long-lasting secondary mechanical hyperalgesia and slower onset secondary heat hypoalgesia (1day after the capsaicin treatment). Between treatments of different acupoints, capsaicin administrated into the ST36 acupoint exhibited the stronger pain intensity and more widespread pain distribution compared with the treatment of ST37 acupoint. A period of 30- to 45-min, but not 15-min, 43°C heating-needle stimulation applied to the ST36 acupoint significantly enhanced the HPT, and had no effect on PPT. Upon trapezius muscle pain elicited by the i.m. injection of 5.8% saline, pre-emptive treatment of the contralateral ST36 acupoint with 43°C heating-needle stimulation alleviated the ongoing muscle pain, reduced painful area, and reversed the decrease in HPT. It is suggested that (1) pain elicited from the acupoint and non-acupoint areas differs significantly, which are supposed to be dependent on the different distributions and contributions of capsaicin-sensitive afferents. (2) Non-painful heat stimulation is a valid approach in prevention of ongoing muscle pain with associated post-effects of peripheral and central sensitization. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Kinin B1 receptors contributes to acute pain following minor surgery in humans

    Directory of Open Access Journals (Sweden)

    Brahim Jaime S

    2010-02-01

    Full Text Available Abstract Background Kinins play an important role in regulation of pain and hyperalgesia after tissue injury and inflammation by activating two types of G-protein-coupled receptors, the kinin B1 and B2 receptors. It is generally accepted that the B2 receptor is constitutively expressed, whereas the B1 receptor is induced in response to inflammation. However, little is known about the regulatory effects of kinin receptors on the onset of acute inflammation and inflammatory pain in humans. The present study investigated the changes in gene expression of kinin receptors and the levels of their endogenous ligands at an early time point following tissue injury and their relation to clinical pain, as well as the effect of COX-inhibition on their expression levels. Results Tissue injury resulted in a significant up-regulation in the gene expression of B1 and B2 receptors at 3 hours post-surgery, the onset of acute inflammatory pain. Interestingly, the up-regulation in the gene expression of B1 and B2 receptors was positively correlated to pain intensity only after ketorolac treatment, signifying an interaction between prostaglandins and kinins in the inflammatory pain process. Further, the gene expression of both B1 and B2 receptors were correlated. Following tissue injury, B1 ligands des-Arg9-BK and des-Arg10-KD were significantly lower at the third hour compared to the first 2 hours in both the placebo and the ketorolac treatment groups but did not differ significantly between groups. Tissue injury also resulted in the down-regulation of TRPV1 gene expression at 3 hours post-surgery with no significant effect by ketorolac treatment. Interestingly, the change in gene expression of TRPV1 was correlated to the change in gene expression of B1 receptor but not B2 receptor. Conclusions These results provide evidence at the transcriptional level in a clinical model of tissue injury that up-regulation of kinin receptors are involved in the development of the

  15. Hyperalgesia in a human model of acute inflammatory pain: a methodological study

    DEFF Research Database (Denmark)

    Pedersen, J L; Kehlet, H

    1998-01-01

    as significant for all variables with fewer than 12 subjects in a cross-over design (2alpha = 5% and power = 80%). Between-day comparisons demanded up to 25 subjects to detect changes of the same magnitude. The burns caused mild to moderate pain (VAS: mean 29, SD 14) and the subjects (all right-handed) were more......The aim of the study was to examine reproducibility of primary and secondary hyperalgesia in a psychophysical model of human inflammatory pain. Mild burns were produced on the crura of 12 volunteers with a 50 x 25 mm thermode (47 degrees C, 7 min). Assessments of (i) cold and warm detection...... thresholds, (ii) mechanical and heat pain thresholds, (iii) pain to heat (43 degrees C and 45 degrees C, 5 s), (iv) secondary hyperalgesia, and (v) skin erythema were made 1.75 and 0.5 h before, and 0, 1, 2, 4, and 6 h after a burn injury. Sensory thresholds and hyperalgesia to heat and mechanical stimuli...

  16. Experimental annotation of the human genome using microarray technology.

    Science.gov (United States)

    Shoemaker, D D; Schadt, E E; Armour, C D; He, Y D; Garrett-Engele, P; McDonagh, P D; Loerch, P M; Leonardson, A; Lum, P Y; Cavet, G; Wu, L F; Altschuler, S J; Edwards, S; King, J; Tsang, J S; Schimmack, G; Schelter, J M; Koch, J; Ziman, M; Marton, M J; Li, B; Cundiff, P; Ward, T; Castle, J; Krolewski, M; Meyer, M R; Mao, M; Burchard, J; Kidd, M J; Dai, H; Phillips, J W; Linsley, P S; Stoughton, R; Scherer, S; Boguski, M S

    2001-02-15

    The most important product of the sequencing of a genome is a complete, accurate catalogue of genes and their products, primarily messenger RNA transcripts and their cognate proteins. Such a catalogue cannot be constructed by computational annotation alone; it requires experimental validation on a genome scale. Using 'exon' and 'tiling' arrays fabricated by ink-jet oligonucleotide synthesis, we devised an experimental approach to validate and refine computational gene predictions and define full-length transcripts on the basis of co-regulated expression of their exons. These methods can provide more accurate gene numbers and allow the detection of mRNA splice variants and identification of the tissue- and disease-specific conditions under which genes are expressed. We apply our technique to chromosome 22q under 69 experimental condition pairs, and to the entire human genome under two experimental conditions. We discuss implications for more comprehensive, consistent and reliable genome annotation, more efficient, full-length complementary DNA cloning strategies and application to complex diseases.

  17. The effect of spinal manipulation on deep experimental muscle pain in healthy volunteers

    DEFF Research Database (Denmark)

    O'Neill, Søren; Ødegaard-Olsen, Øystein; Søvde, Beate

    2015-01-01

    individuals. METHODS AND MATERIALS: Local, para-spinal muscle pain was induced by injection of 0.5 ml sterile, hyper-tonic saline on two separate occasions 1 week apart. Immediately following the injection, treatment was administered as either a) HVLA-manipulation or b) placebo treatment, in a randomized...

  18. Towards a physiology-based measure of pain: patterns of human brain activity distinguish painful from non-painful thermal stimulation.

    Directory of Open Access Journals (Sweden)

    Justin E Brown

    Full Text Available Pain often exists in the absence of observable injury; therefore, the gold standard for pain assessment has long been self-report. Because the inability to verbally communicate can prevent effective pain management, research efforts have focused on the development of a tool that accurately assesses pain without depending on self-report. Those previous efforts have not proven successful at substituting self-report with a clinically valid, physiology-based measure of pain. Recent neuroimaging data suggest that functional magnetic resonance imaging (fMRI and support vector machine (SVM learning can be jointly used to accurately assess cognitive states. Therefore, we hypothesized that an SVM trained on fMRI data can assess pain in the absence of self-report. In fMRI experiments, 24 individuals were presented painful and nonpainful thermal stimuli. Using eight individuals, we trained a linear SVM to distinguish these stimuli using whole-brain patterns of activity. We assessed the performance of this trained SVM model by testing it on 16 individuals whose data were not used for training. The whole-brain SVM was 81% accurate at distinguishing painful from non-painful stimuli (p<0.0000001. Using distance from the SVM hyperplane as a confidence measure, accuracy was further increased to 84%, albeit at the expense of excluding 15% of the stimuli that were the most difficult to classify. Overall performance of the SVM was primarily affected by activity in pain-processing regions of the brain including the primary somatosensory cortex, secondary somatosensory cortex, insular cortex, primary motor cortex, and cingulate cortex. Region of interest (ROI analyses revealed that whole-brain patterns of activity led to more accurate classification than localized activity from individual brain regions. Our findings demonstrate that fMRI with SVM learning can assess pain without requiring any communication from the person being tested. We outline tasks that should be

  19. Jaw-motor effects of experimental jaw-muscle pain and stress in patients with deep bite and matched control subjects

    DEFF Research Database (Denmark)

    Sonnesen, Liselotte; Svensson, Peter

    2013-01-01

    clenching, during evoked pain and stress between deep bite patients and controls was investigated. DESIGN: In 30 deep bite patients and in 30 sex-/age-matched controls with neutral occlusion EMG activity was recorded bilaterally from masseter and anterior temporalis muscles before and during evoked pain......OBJECTIVE: The effect of experimental jaw-muscle pain and stress on masticatory muscle activity in TMD-patients has been discussed. Furthermore, associations between TMD and deep bite patients have been studied. Accordingly in the present study, comparison of EMG responses at rest, maximal...... and before and during a stress task. Evoked pain was induced by injections of glutamate into the masseter (local pain) and brachioradialis (remote pain) muscles and resting EMG activity was recorded before and after 1, 2, 3, 4, 5 and 10min. A precision task was used to simulate a stressful condition and EMG...

  20. Effect of peripheral morphine in a human model of acute inflammatory pain

    DEFF Research Database (Denmark)

    Lillesø, J; Hammer, N A; Pedersen, J L

    2000-01-01

    Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo-controlled, th......Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo......-controlled, three-way crossover design in a human model of acute inflammatory pain (heat injury). We studied 18 healthy volunteers who each received morphine locally (2 mg), morphine systemically (2 mg), or placebo on three separate study days. The subjects received morphine infiltration subcutaneously (s.c.). 1 h......, but local morphine infiltration neither reduced pain during the burn, nor primary or secondary hyperalgesia to mechanical and heat stimuli after the burn. In conclusion, peripherally applied morphine had no acute antinociceptive effects in this human model of acute inflammatory pain....

  1. Peripheral and central components of habituation of heat pain perception and evoked potentials in humans.

    Science.gov (United States)

    Greffrath, Wolfgang; Baumgärtner, Ulf; Treede, Rolf-Detlef

    2007-12-05

    For the neurophysiological examination of nociceptive pathways, contact-heat evoked potentials (contact-heat EPs) are elicited by repetitive brief noxious heat stimuli. Suppression of heat responses in primary nociceptive neurons during repetitive stimulation has been shown in animal models in vivo and in vitro. We now investigated whether heat pain and contact-heat EPs in humans display equivalent signs of habituation. Heat pain and EPs were elicited in 16 volunteers with a contact thermode (30 degrees Cs(-1)). Heat pulses at three intensities (pain threshold, moderate noxious and maximum available) were applied to the right forearm either by moving the thermode after each pulse to variable locations or when fixed to one location (inter-stimulus intervals 8-10s). Contact-heat EPs consisted of an early negativity in temporal leads (N1), followed by a biphasic response at the vertex (N2-P2). Pain ratings and contact-heat EPs (N1 and N2-P2 components) displayed significant temperature dependence. N2-P2 correlated positively with ratings. With stimulation at variable locations, both measures slowly decreased with time constants tau of 2 min (ratings) and 12 min (EPs). With stimulation at a fixed location, habituation was much faster for both, ratings (tau=10s) and EPs (tau=33 s). As a consequence, both measures were significantly reduced (pheat pain perception and contact-heat EPs display signs of rapid habituation when stimulation is restricted to a fixed location and thus, reflect fatigue of peripheral nociceptive neurons. Habituation within the central nervous system is slower and less pronounced.

  2. Intradiscal application of a PCLA-PEG-PCLA hydrogel loaded with celecoxib for the treatment of back pain in canines: What's in it for humans?

    Science.gov (United States)

    Tellegen, Anna R; Willems, Nicole; Beukers, Martijn; Grinwis, Guy C M; Plomp, Saskia G M; Bos, Clemens; van Dijk, Maarten; de Leeuw, Mike; Creemers, Laura B; Tryfonidou, Marianna A; Meij, Björn P

    2018-03-01

    Chronic low back pain is a common clinical problem in both the human and canine population. Current pharmaceutical treatment often consists of oral anti-inflammatory drugs to alleviate pain. Novel treatments for degenerative disc disease focus on local application of sustained released drug formulations. The aim of this study was to determine safety and feasibility of intradiscal application of a poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-bpoly(ε-caprolactone-co-lactide) PCLA-PEG-PCLA hydrogel releasing celecoxib, a COX-2 inhibitor. Biocompatibility was evaluated after subcutaneous injection in mice, and safety of intradiscal injection of the hydrogel was evaluated in experimental dogs with early spontaneous intervertebral disc (IVD) degeneration. COX-2 expression was increased in IVD samples surgically obtained from canine patients, indicating a role of COX-2 in clinical IVD disease. Ten client-owned dogs with chronic low back pain related to IVD degeneration received an intradiscal injection with the celecoxib-loaded hydrogel. None of the dogs showed adverse reactions after intradiscal injection. The hydrogel did not influence magnetic resonance imaging signal at long-term follow-up. Clinical improvement was achieved by reduction of back pain in 9 of 10 dogs, as was shown by clinical examination and owner questionnaires. In 3 of 10 dogs, back pain recurred after 3 months. This study showed the safety and effectiveness of intradiscal injections in vivo with a thermoresponsive PCLA-PEG-PCLA hydrogel loaded with celecoxib. In this set-up, the dog can be used as a model for the development of novel treatment modalities in both canine and human patients with chronic low back pain. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Simultaneous fMRI-PET of the opioidergic pain system in human brain

    DEFF Research Database (Denmark)

    Wey, Hsiao-Ying; Catana, Ciprian; Hooker, Jacob M

    2014-01-01

    distinct components of the blood oxygenation level dependent (BOLD) fMRI signal has not yet been shown. We obtained sixteen fMRI-PET data sets from eight healthy volunteers. Each subject participated in randomized order in a pain scan and a control (nonpainful pressure) scan on the same day. Dynamic PET......MRI and PET provide complementary information for studying brain function. While the potential use of simultaneous MRI/PET for clinical diagnostic and disease staging has been demonstrated recently; the biological relevance of concurrent functional MRI-PET brain imaging to dissect neurochemically...... data were acquired with an opioid radioligand, [(11)C]diprenorphine, to detect endogenous opioid releases in response to pain. BOLD fMRI data were collected at the same time to capture hemodynamic responses. In this simultaneous human fMRI-PET imaging study, we show co-localized responses in thalamus...

  4. Experimental metagenomics and ribosomal profiling of the human skin microbiome.

    Science.gov (United States)

    Ferretti, Pamela; Farina, Stefania; Cristofolini, Mario; Girolomoni, Giampiero; Tett, Adrian; Segata, Nicola

    2017-03-01

    The skin is the largest organ in the human body, and it is populated by a large diversity of microbes, most of which are co-evolved with the host and live in symbiotic harmony. There is increasing evidence that the skin microbiome plays a crucial role in the defense against pathogens, immune system training and homoeostasis, and microbiome perturbations have been associated with pathological skin conditions. Studying the skin resident microbial community is thus essential to better understand the microbiome-host crosstalk and to associate its specific configurations with cutaneous diseases. Several community profiling approaches have proved successful in unravelling the composition of the skin microbiome and overcome the limitations of cultivation-based assays, but these tools remain largely inaccessible to the clinical and medical dermatology communities. The study of the skin microbiome is also characterized by specific technical challenges, such as the low amount of microbial biomass and the extensive human DNA contamination. Here, we review the available community profiling approaches to study the skin microbiome, specifically focusing on the practical experimental and analytical tools necessary to generate and analyse skin microbiome data. We describe all the steps from the initial samples collection to the final data interpretation, with the goal of enabling clinicians and researchers who are not familiar with the microbiome field to perform skin profiling experiments. © 2016 The Authors. Experimental Dermatology Published by John Wiley & Sons Ltd.

  5. Numerical and experimental investigations of human swimming motions.

    Science.gov (United States)

    Takagi, Hideki; Nakashima, Motomu; Sato, Yohei; Matsuuchi, Kazuo; Sanders, Ross H

    2016-08-01

    This paper reviews unsteady flow conditions in human swimming and identifies the limitations and future potential of the current methods of analysing unsteady flow. The capability of computational fluid dynamics (CFD) has been extended from approaches assuming steady-state conditions to consideration of unsteady/transient conditions associated with the body motion of a swimmer. However, to predict hydrodynamic forces and the swimmer's potential speeds accurately, more robust and efficient numerical methods are necessary, coupled with validation procedures, requiring detailed experimental data reflecting local flow. Experimental data obtained by particle image velocimetry (PIV) in this area are limited, because at present observations are restricted to a two-dimensional 1.0 m(2) area, though this could be improved if the output range of the associated laser sheet increased. Simulations of human swimming are expected to improve competitive swimming, and our review has identified two important advances relating to understanding the flow conditions affecting performance in front crawl swimming: one is a mechanism for generating unsteady fluid forces, and the other is a theory relating to increased speed and efficiency.

  6. Experimental pain processing in individuals with cognitive impairment: current state of the science

    DEFF Research Database (Denmark)

    Defrin, R; Amanzio, Martina; de Tomasso, M

    2015-01-01

    Cognitive impairment (CI) can develop during the course of ageing and is a feature of many neurological and neurodegenerative diseases. Many individuals with CI have substantial, sustained and complex healthcare needs which frequently include pain. However, individuals with CI can have difficulty...... of neurological and neurodegenerative disorders in which CI is typically present. Overall, the existing data suggest that pain processing is altered in most individuals with CI compared to cognitively intact matched controls. The precise nature of these alterations varies with the type of CI (or associated...... to cognitively unimpaired individuals. Our current understanding of the neurobiological mechanisms underpinning these alterations is limited, but may be enhanced through the use of animal models of CI which also exhibit alterations in nociceptive responding. Further research employing additional behavioural...

  7. Modelling the PKPD of oxycodone in experimental pain - impact of opioid receptor polymorphisms

    DEFF Research Database (Denmark)

    Olsen, Rasmus; Foster, David J R; Upton, Richard N

    2016-01-01

    BACKGROUND: Polymorphisms in the opioid receptor genes may affect the pharmacodynamics (PD) of oxycodone and be part of the reason behind the diversity in clinical response. The aim of the analysis was to model the exposure-response profile of oxycodone for three different pain variables and search...... for genetic covariates. Model simulations were used to predict how population and effect-size impact the power to detect clinical significant SNPs. METHOD: The population pharmacokinetic-pharmacodynamic (PKPD) model of oral single-dosed oxycodone was based on pooled data from three published studies...... in healthy volunteers. Pain tolerance data from muscle pressure (n=36), visceral pressure (n=54) and skin pinch (n=34) were included. Genetic associations with 18 opioid-receptor SNPs were explored using a stepwise covariate approach. Model simulations were performed using the estimated model parameters...

  8. Autonomic nervous system function in patients with functional abdominal pain. An experimental study

    DEFF Research Database (Denmark)

    Jorgensen, L.S.; Christiansen, P.; Raundahl, U.

    1993-01-01

    Functional abdominal pain--that is, pain without demonstrable organic abnormalities--has often been associated with psychologic stress. The aim of the present study was to investigate whether sympathetic nervous system response to laboratory stress and basal parasympathetic neural activity were...... and serum cortisol did not increase at all in any of the groups. As a measure of parasympathetic neural activity, independent of sympathetic neural activity, the beat-to-beat variation of the heart rate was calculated. The functional patients had a significantly higher beat-to-beat variation expressed...... as the mean square successive differences of the R-R intervals (MSSD), indicating a higher basal parasympathetic neural activity (mean MSSD +/- SEM = 64 +/- 6 msec in the functional group, 46 +/- 6 msec in the healthy group, and 49 +/- 6 msec in the organic group; P = 0.03). A reduced sympathetic neural...

  9. The effects of anger and sadness on clinical pain reports and experimentally-induced pain thresholds in women with and without fibromyalgia.

    NARCIS (Netherlands)

    Middendorp, H. van; Lumley, M.A.; Jacobs, J.W.G.; Bijlsma, J.W.J.; Geenen, R.

    2010-01-01

    OBJECTIVE: Negative emotions are commonly experienced in fibromyalgia and may affect pain. This study examined the effects of anger and sadness on clinical pain reports and on pain threshold and tolerance in response to electrical stimulation in women with and without fibromyalgia. METHODS: In an

  10. Association Between Human Pain-Related Genotypes and Variability in Opioid Analgesia

    DEFF Research Database (Denmark)

    Nielsen, Lecia M; Olesen, Anne E; Branford, Ruth

    2015-01-01

    On an individual level, there is a difference in the analgesic response to a given opioid. Various factors such as gender, age, and genetic variation can affect the analgesic response. The genetic variation can influence pharmacokinetics (eg drug transporters and drug-metabolizing enzymes) and...... as opioid consumption or changes in pain scores. Studies have shown promising results regarding pharmacogenetics as a diagnostic tool for predicting the individual response to a given opioid in the experimental settings; however, in the clinic, it is a more complicated task to accomplish....

  11. Pain Intervention for people with Dementia in nursing homes (PID): study protocol for a quasi-experimental nurse intervention.

    Science.gov (United States)

    Koppitz, Andrea; Bosshard, Georg; Blanc, Geneviève; Hediger, Hannele; Payne, Sheila; Volken, Thomas

    2017-04-21

    It is estimated that 19 to 83% of people with dementia suffer from pain that is inadequately treated in the last months of life. A large number of healthcare workers who care for these people in nursing homes lack appropriate expertise and may therefore not always recognise, assess and treat pain in those with dementia who have complex problems on time, properly and efficiently. The aim of this intervention trial is to identify care needs of people with dementia suffering from pain living in a nursing home. A quasi-experimental nurse-led intervention trial based on a convenience sample of four nursing homes in the Swiss Canton of Zurich examines the effects on dementia patients (n = 411), the healthcare institution and the qualification level of the healthcare workers compared to historical controls, using an event analysis and a multilevel analysis. Healthcare workers will be individually trained how to assess, intervene and evaluate acute and chronic pain. There are three data-monitoring cycles (T0, T1, T2) and two intervention cycles (I1, I2) with a total study duration of 425 days. There is also a process evaluation based on Dobbins analyses that analyse in particular the potentials for change in clinical practice of change agents. The aim of the intervention trial is to improve pain management strategies in older people with dementia in nursing homes. Clinically significant findings will be expected that will help reduce suffering in the sense of "total pain" for people with dementia. The joint intra- and interdisciplinary collaboration between practice and supply-oriented (nursing) research will have both a lasting effect on the efficiency measurement and provide scientifically sound results. Nursing homes can integrate the findings from the intervention trial into their internal quality control process. The potential for improvements can be directly influenced by the nursing home itself. Registration trial number: DRKS00009726 on DRKS, registered 10

  12. The Non-Human Primate Experimental Glaucoma Model

    Science.gov (United States)

    Burgoyne, Claude F.

    2015-01-01

    The purpose of this report is to summarize the current strengths and weaknesses of the non-human primate (NHP) experimental glaucoma (EG) model through sections devoted to its history, methods, important findings, alternative optic neuropathy models and future directions. NHP EG has become well established for studying human glaucoma in part because the NHP optic nerve head (ONH) shares a close anatomic association with the human ONH and because it provides the only means of systematically studying the very earliest visual system responses to chronic IOP elevation, i.e. the conversion from ocular hypertension to glaucomatous damage. However, NHPs are impractical for studies that require large animal numbers, demonstrate spontaneous glaucoma only rarely, do not currently provide a model of the neuropathy at normal levels of IOP, and cannot easily be genetically manipulated, except through tissue-specific, viral vectors. The goal of this summary is to direct NHP EG and non-NHP EG investigators to the previous, current and future accomplishment of clinically relevant knowledge in this model. PMID:26070984

  13. Animal experimentation

    OpenAIRE

    Laz, Alak; Cholakova, Tanya Stefanova; Vrablova, Sofia; Arshad, Naverawaheed

    2016-01-01

    Animal experimentation is a crucial part of medical science. One of the ways to define it is any scientific experiment conducted for research purposes that cause any kind of pain or suffering to animals. Over the years, the new discovered drugs or treatments are first applied on animals to test their positive outcomes to be later used by humans. There is a debate about violating ethical considerations by exploiting animals for human benefits. However, different ethical theories have been made...

  14. Influence of Polymorphisms in the HTR3A and HTR3B Genes on Experimental Pain and the Effect of the 5-HT3 Antagonist Granisetron.

    Science.gov (United States)

    Louca Jounger, Sofia; Christidis, Nikolaos; Hedenberg-Magnusson, Britt; List, Thomas; Svensson, Peter; Schalling, Martin; Ernberg, Malin

    2016-01-01

    The aim of this study was to investigate experimentally if 5-HT3 single nucleotide polymorphisms (SNP) contribute to pain perception and efficacy of the 5-HT3-antagonist granisetron and sex differences. Sixty healthy participants were genotyped regarding HTR3A (rs1062613) and HTR3B (rs1176744). First, pain was induced by bilateral hypertonic saline injections (HS, 5.5%, 0.2 mL) into the masseter muscles. Thirty min later the masseter muscle on one side was pretreated with 0.5 mL granisetron (1 mg/mL) and on the other side with 0.5 mL placebo (isotonic saline) followed by another HS injection (0.2 mL). Pain intensity, pain duration, pain area and pressure pain thresholds (PPTs) were assessed after each injection. HS evoked moderate pain, with higher intensity in the women (P = 0.023), but had no effect on PPTs. None of the SNPs influenced any pain variable in general, but compared to men, the pain area was larger in women carrying the C/C (HTR3A) (P = 0.015) and pain intensity higher in women with the A/C alleles (HTR3B) (P = 0.019). Pre-treatment with granisetron reduced pain intensity, duration and area to a lesser degree in women (P granisetron. Women carrying the C/T & T/T (HTR3A) genotype had less reduction of pain intensity (P = 0.041) and area (P = 0.005), and women with the C/C genotype (HTR3B) had less reduction of pain intensity (P = 0.030), duration (P = 0.030) and area compared to men (P = 0.017). In conclusion, SNPs did not influence experimental muscle pain or the effect of granisetron on pain variables in general, but there were some sex differences in pain variables that seem to be influenced by genotypes. However, due to the small sample size further research is needed before any firm conclusions can be drawn.

  15. Influence of Polymorphisms in the HTR3A and HTR3B Genes on Experimental Pain and the Effect of the 5-HT3 Antagonist Granisetron.

    Directory of Open Access Journals (Sweden)

    Sofia Louca Jounger

    Full Text Available The aim of this study was to investigate experimentally if 5-HT3 single nucleotide polymorphisms (SNP contribute to pain perception and efficacy of the 5-HT3-antagonist granisetron and sex differences. Sixty healthy participants were genotyped regarding HTR3A (rs1062613 and HTR3B (rs1176744. First, pain was induced by bilateral hypertonic saline injections (HS, 5.5%, 0.2 mL into the masseter muscles. Thirty min later the masseter muscle on one side was pretreated with 0.5 mL granisetron (1 mg/mL and on the other side with 0.5 mL placebo (isotonic saline followed by another HS injection (0.2 mL. Pain intensity, pain duration, pain area and pressure pain thresholds (PPTs were assessed after each injection. HS evoked moderate pain, with higher intensity in the women (P = 0.023, but had no effect on PPTs. None of the SNPs influenced any pain variable in general, but compared to men, the pain area was larger in women carrying the C/C (HTR3A (P = 0.015 and pain intensity higher in women with the A/C alleles (HTR3B (P = 0.019. Pre-treatment with granisetron reduced pain intensity, duration and area to a lesser degree in women (P < 0.05, but the SNPs did not in general influence the efficacy of granisetron. Women carrying the C/T & T/T (HTR3A genotype had less reduction of pain intensity (P = 0.041 and area (P = 0.005, and women with the C/C genotype (HTR3B had less reduction of pain intensity (P = 0.030, duration (P = 0.030 and area compared to men (P = 0.017. In conclusion, SNPs did not influence experimental muscle pain or the effect of granisetron on pain variables in general, but there were some sex differences in pain variables that seem to be influenced by genotypes. However, due to the small sample size further research is needed before any firm conclusions can be drawn.

  16. A theory-based educational intervention targeting nurses' attitudes and knowledge concerning cancer-related pain management: A study protocol of a quasi-experimental design

    Directory of Open Access Journals (Sweden)

    Gustafsson Markus

    2011-09-01

    Full Text Available Abstract Background Pain is one of the most frequent problems among patients diagnosed with cancer. Despite the availability of effective pharmacological treatments, this group of patients often receives less than optimal treatment. Research into nurses' pain management highlights certain factors, such as lack of knowledge and attitudes and inadequate procedures for systematic pain assessment, as common barriers to effective pain management. However, educational interventions targeting nurses' pain management have shown promise. As cancer-related pain is also known to have a negative effect on vital aspects of the patient's life, as well as being commonly associated with problems such as sleep, fatigue, depression and anxiety, further development of knowledge within this area is warranted. Methods/design A quasi-experimental study design will be used to investigate whether the implementation of guidelines for systematic daily pain assessments following a theory-based educational intervention will result in an improvement in knowledge and attitude among nurses. A further aim is to investigate whether the intervention that targets nurses' behaviour will improve hospital patients' perception of pain. Data regarding nurses' knowledge and attitudes to pain (primary outcome, patient perception regarding pain (secondary outcome, together with socio-demographic variables, will be collected at baseline and at four weeks and 12 weeks following the intervention. Discussion Nursing care is nowadays acknowledged as an increasingly complicated activity and "nursing complexity is such that it can be seen as the quintessential complex intervention." To be able to change and improve clinical practice thus requires multiple points of attack appropriate to meet complex challenges. Consequently, we expect the theory-based intervention used in our quasi-experimental study to improve care as well as quality of life for this group of patients and we also envisage that

  17. A theory-based educational intervention targeting nurses' attitudes and knowledge concerning cancer-related pain management: a study protocol of a quasi-experimental design.

    Science.gov (United States)

    Borglin, Gunilla; Gustafsson, Markus; Krona, Hans

    2011-09-23

    Pain is one of the most frequent problems among patients diagnosed with cancer. Despite the availability of effective pharmacological treatments, this group of patients often receives less than optimal treatment. Research into nurses' pain management highlights certain factors, such as lack of knowledge and attitudes and inadequate procedures for systematic pain assessment, as common barriers to effective pain management. However, educational interventions targeting nurses' pain management have shown promise. As cancer-related pain is also known to have a negative effect on vital aspects of the patient's life, as well as being commonly associated with problems such as sleep, fatigue, depression and anxiety, further development of knowledge within this area is warranted. A quasi-experimental study design will be used to investigate whether the implementation of guidelines for systematic daily pain assessments following a theory-based educational intervention will result in an improvement in knowledge and attitude among nurses. A further aim is to investigate whether the intervention that targets nurses' behaviour will improve hospital patients' perception of pain. Data regarding nurses' knowledge and attitudes to pain (primary outcome), patient perception regarding pain (secondary outcome), together with socio-demographic variables, will be collected at baseline and at four weeks and 12 weeks following the intervention. Nursing care is nowadays acknowledged as an increasingly complicated activity and "nursing complexity is such that it can be seen as the quintessential complex intervention." To be able to change and improve clinical practice thus requires multiple points of attack appropriate to meet complex challenges. Consequently, we expect the theory-based intervention used in our quasi-experimental study to improve care as well as quality of life for this group of patients and we also envisage that evidence-based guidelines targeting this patient group's pain

  18. Reduced thoracolumbar fascia shear strain in human chronic low back pain

    Directory of Open Access Journals (Sweden)

    Konofagou Elisa E

    2011-09-01

    Full Text Available Abstract Background The role played by the thoracolumbar fascia in chronic low back pain (LBP is poorly understood. The thoracolumbar fascia is composed of dense connective tissue layers separated by layers of loose connective tissue that normally allow the dense layers to glide past one another during trunk motion. The goal of this study was to quantify shear plane motion within the thoracolumbar fascia using ultrasound elasticity imaging in human subjects with and without chronic low back pain (LBP. Methods We tested 121 human subjects, 50 without LBP and 71 with LBP of greater than 12 months duration. In each subject, an ultrasound cine-recording was acquired on the right and left sides of the back during passive trunk flexion using a motorized articulated table with the hinge point of the table at L4-5 and the ultrasound probe located longitudinally 2 cm lateral to the midline at the level of the L2-3 interspace. Tissue displacement within the thoracolumbar fascia was calculated using cross correlation techniques and shear strain was derived from this displacement data. Additional measures included standard range of motion and physical performance evaluations as well as ultrasound measurement of perimuscular connective tissue thickness and echogenicity. Results Thoracolumbar fascia shear strain was reduced in the LBP group compared with the No-LBP group (56.4% ± 3.1% vs. 70.2% ± 3.6% respectively, p Conclusion Thoracolumbar fascia shear strain was ~20% lower in human subjects with chronic low back pain. This reduction of shear plane motion may be due to abnormal trunk movement patterns and/or intrinsic connective tissue pathology. There appears to be some sex-related differences in thoracolumbar fascia shear strain that may also play a role in altered connective tissue function.

  19. A novel magnetic stimulator increases experimental pain tolerance in healthy volunteers - a double-blind sham-controlled crossover study.

    Directory of Open Access Journals (Sweden)

    Rudie Kortekaas

    Full Text Available UNLABELLED: The 'complex neural pulse'(TM (CNP is a neuromodulation protocol employing weak pulsed electromagnetic fields (PEMF. A pioneering paper reported an analgesic effect in healthy humans after 30 minutes of CNP-stimulation using three nested whole head coils. We aimed to devise and validate a stimulator with a novel design entailing a multitude of small coils at known anatomical positions on a head cap, to improve applicability. The main hypothesis was that CNP delivery with this novel device would also increase heat pain thresholds. Twenty healthy volunteers were enrolled in this double-blind, sham-controlled, crossover study. Thirty minutes of PEMF (CNP or sham was applied to the head. After one week the other treatment was given. Before and after each treatment, primary and secondary outcomes were measured. Primary outcome was heat pain threshold (HPT measured with thermal quantitative sensory testing. Other outcomes were warmth detection threshold, and aspects of cognition, emotion and motor performance. As hypothesized heat pain threshold was significantly increased after the PEMF stimulation. All other outcomes were unaltered by the PEMF but there was a trend level reduction of cognitive performance after PEMF stimulation as measured by the digit-symbol substitution task. Results from this pilot study suggest that our device is able to stimulate the brain and to modulate its function. This is in agreement with previous studies that used similar magnetic field strengths to stimulate the brain. Specifically, pain control may be achieved with PEMF and for this analgesic effect, coil design does not appear to play a dominant role. In addition, the flexible configuration with small coils on a head cap improves clinical applicability. TRIAL REGISTRATION: Dutch Cochrane Centre NTR1093.

  20. Experimental pain ratings and reactivity of cortisol and soluble tumor necrosis factor-α receptor II following a trial of hypnosis: Results of a randomized controlled pilot study

    Science.gov (United States)

    Goodin, Burel R.; Quinn, Noel B.; Kronfli, Tarek; King, Christopher D.; Page, Gayle G.; Haythornthwaite, Jennifer A.; Edwards, Robert R.; Stapleton, Laura M.; McGuire, Lynanne

    2011-01-01

    Objective Current evidence supports the efficacy of hypnosis for reducing the pain associated with experimental stimulation and various acute and chronic conditions; however, the mechanisms explaining how hypnosis exerts its effects remain less clear. The hypothalamic-pituitary-adrenal (HPA) axis and pro-inflammatory cytokines represent potential targets for investigation given their purported roles in the perpetuation of painful conditions; yet, no clinical trials have thus far examined the influence of hypnosis on these mechanisms. Design Healthy participants, highly susceptible to the effects of hypnosis, were randomized to either a hypnosis intervention or a no-intervention control. Using a cold pressor task, assessments of pain intensity and pain unpleasantness were collected prior to the intervention (Pre) and following the intervention (Post) along with pain-provoked changes in salivary cortisol and the soluble receptor of tumor necrosis factor-α (sTNFαRII). Results Compared to the no-intervention control, data analyses revealed that hypnosis significantly reduced pain intensity and pain unpleasantness. Hypnosis was not significantly associated with suppression of cortisol or sTNFαRII reactivity to acute pain from Pre to Post; however, the effect sizes for these associations were medium-sized. Conclusions Overall, the findings from this randomized controlled pilot study support the importance of a future large-scale study on the effects of hypnosis for modulating pain-related changes of the HPA axis and pro-inflammatory cytokines. PMID:22233394

  1. Relevance of physical fitness levels and exercise-related beliefs for self-reported and experimental pain in fibromyalgia: an explorative study.

    Science.gov (United States)

    de Bruijn, Saskia T; van Wijck, Albert J M; Geenen, Rinie; Snijders, Tom J; van der Meulen, Wout J T M; Jacobs, Johannes W G; Veldhuijzen, Dieuwke Swaantje

    2011-09-01

    It has been suggested that low physical fitness is a contributor to pain in fibromyalgia and that exercise-related beliefs play a role in the persistence of this association. Yet the association between physical fitness and pain is hardly explored in detail. The aim of this exploratory study in patients with fibromyalgia was to investigate the association of physical fitness levels with self-reported and experimental pain as well as with pain catastrophizing and activity-avoidance beliefs. Physical fitness of 18 patients with fibromyalgia was examined using maximal ergocycling and the 6-minute walking test (6MWT). Pain intensity was assessed using self-report scales and quantitative sensory testing. A reduced walking distance on the 6MWT was correlated with more severe self-reported pain on the Fibromyalgia Impact Questionnaire (r = -0.52, P physically fit and experienced more severe pain. The results demonstrate some associations between physical fitness and pain in fibromyalgia and point to the importance of activity avoidance. Although the causal directionality of the associations needs substantiation in clinical research, the findings support the notion that low fitness and activity-avoidance beliefs should be targeted while treating pain in fibromyalgia.

  2. Can a theory-based educational intervention change nurses' knowledge and attitudes concerning cancer pain management? A quasi-experimental design.

    Science.gov (United States)

    Gustafsson, Markus; Borglin, Gunilla

    2013-08-19

    Registered Nurses (RNs) play an important role in caring for patients suffering from cancer pain. A lack of knowledge regarding pain management and the RNs' own perception of cancer pain could act as barriers to effective pain management. Educational interventions that target RNs' knowledge and attitudes have proved promising. However, an intervention consisting of evidence-based practice is a multifaceted process and demands behavioural and cognitive changes to sustain the effects of the intervention. Therefore, our study aimed to investigate if a theory-based educational intervention could change RNs' knowledge and attitudes to cancer pain and pain management, both four and 12 weeks after the start of the intervention. A quasi-experimental design with non-equivalent control groups was used. The primary outcome was measured using a modified version of the instrument Nurses' Knowledge and Attitudes Survey Regarding Pain (NKAS) at baseline, four weeks and 12 weeks after the start of the intervention to evaluate its persistence. The intervention's educational curriculum was based on the principles of Ajzen's Theory of Planned Behaviour and consisted of interactive learning activities conducted in workshops founded on evidence-based knowledge. The RN's own experiences from cancer pain management were used in the learning process. The theory-based educational intervention aimed at changing RNs knowledge and attitudes regarding cancer pain management measured by primary outcome NKAS resulted in a statistical significant (presearched and needs to be evaluated further in larger projects. Clinical Trials. Gov: NCT01313234.

  3. Tanshinone IIA Attenuates Diabetic Peripheral Neuropathic Pain in Experimental Rats via Inhibiting Inflammation

    Directory of Open Access Journals (Sweden)

    Baojian Zhang

    2018-01-01

    Full Text Available Diabetic peripheral neuropathic pain (DPNP is a common and intractable complication of diabetes. Conventional therapies are always not ideal; development of novel drugs is still needed to achieve better pain relief. Recent evidences have demonstrated that inflammation is involved in the onset and maintenance of DPNP. The anti-inflammatory property of Tanshinone IIA (TIIA makes it a promising candidate to block or alter the pain perception. This study was conducted to investigate whether TIIA could attenuate DPNP in streptozotocin- (STZ- induced rats model and its potential mechanisms. TIIA was administered to STZ-induced diabetic rats at the dose of 40 mg/kg once a day for 3 weeks. The effects of TIIA on thermal hyperalgesia and mechanical allodynia were investigated using behavioral tests. The mRNA level and expression of interleukin- (IL- 1β, interleukin- (IL- 6, tumor necrosis factor- (TNF- α, and interleukin- (IL- 10 in the fourth to sixth segments of the dorsal root ganglion (L4–6 DRG were detected by quantitative real-time PCR (qPCR and Western blot. TIIA treatment significantly attenuated mechanical allodynia and thermal hyperalgesia in diabetic rats. In addition, the expression of the proinflammatory cytokines IL-1β, IL-6, and TNF-α was inhibited, and the level of the anti-inflammatory cytokine IL-10 was increased by TIIA. This study demonstrated that TIIA has significant antiallodynic and antihyperalgesic effects in a rat model of STZ-induced DPNP, and the effect may be associated with its anti-inflammation property.

  4. Intradiscal electrothermal treatment for discogenic back pain: experimental investigation and preliminary clinical application

    International Nuclear Information System (INIS)

    Fang Wen; Teng Gaojun; He Shicheng; Guo Jinhe; Deng Gang; Zhu Guangyu; Li Guozhao; Ding Huijuan; Shen Zhiping

    2005-01-01

    Objective: To assess the effectiveness and the safety of IDET for chronic discogenic low back pain. Methods: Standard intradiscal electrothermal treatment were performed in two adjacent disc levels (L3-4, L4-5) of two domestic pigs. MRI were available at pretreatment, posttreatment of 1,2 weeks, and then the two animals were killed respectively at 1,2 weeks after the procedure. The specimens were then undergone thin sectioned and subjected to humatoxylin and eosin staining for histological investigation. 23 patients (totally 29 discs, including L2-3 to L5-S1) with chronic symptoms underwent IDET for clinical study. VAS (Visual Analog Scale) pain scores were collected before the treatment, 1 week and 3 months after the procedure. One way ANOVA was used for statistical analysis. Results: 4 discs of standard IDET models have been set up in two pigs showing normal MRI T2W1 signal of nucleus pulposus immediately after the procedure, but the high signal extent of the central part of the nucleo pulposus shrinked with conspicuous peripheral low signal changes during the following 1-2 W. Degeneration and shrinkage of nucleo-pulposus with lecolized fibrous ring thickening were found pathologically but without damage to nurve roots and epidural sac. 29 discs in 23 patients were performed successfully, without complication. The follow-up evaluation of 1 week and 3 months after the treatment showing significant differences with those before the treatment on was scores 65.3% and 78.9% respectively (P<0.0001). Conclusions: IDET is safe and effective for chronic discogenic low back pain. (authors)

  5. Mutations that Cause Human Disease: A Computational/Experimental Approach

    Energy Technology Data Exchange (ETDEWEB)

    Beernink, P; Barsky, D; Pesavento, B

    2006-01-11

    International genome sequencing projects have produced billions of nucleotides (letters) of DNA sequence data, including the complete genome sequences of 74 organisms. These genome sequences have created many new scientific opportunities, including the ability to identify sequence variations among individuals within a species. These genetic differences, which are known as single nucleotide polymorphisms (SNPs), are particularly important in understanding the genetic basis for disease susceptibility. Since the report of the complete human genome sequence, over two million human SNPs have been identified, including a large-scale comparison of an entire chromosome from twenty individuals. Of the protein coding SNPs (cSNPs), approximately half leads to a single amino acid change in the encoded protein (non-synonymous coding SNPs). Most of these changes are functionally silent, while the remainder negatively impact the protein and sometimes cause human disease. To date, over 550 SNPs have been found to cause single locus (monogenic) diseases and many others have been associated with polygenic diseases. SNPs have been linked to specific human diseases, including late-onset Parkinson disease, autism, rheumatoid arthritis and cancer. The ability to predict accurately the effects of these SNPs on protein function would represent a major advance toward understanding these diseases. To date several attempts have been made toward predicting the effects of such mutations. The most successful of these is a computational approach called ''Sorting Intolerant From Tolerant'' (SIFT). This method uses sequence conservation among many similar proteins to predict which residues in a protein are functionally important. However, this method suffers from several limitations. First, a query sequence must have a sufficient number of relatives to infer sequence conservation. Second, this method does not make use of or provide any information on protein structure, which

  6. Modulation of itch by conditioning itch and pain stimulation in healthy humans

    DEFF Research Database (Denmark)

    Andersen, Hjalte Holm; van Laarhoven, Antoinette I. M.; Elberling, Jesper

    2017-01-01

    Little is known about endogenous descending control of itch. In chronic pain, descending pain inhibition is reduced as signified by lowered conditioned pain modulation (CPM). There are indications that patients with chronic itch may also exhibit reduced endogenous descending inhibition of itch......-evoked itch, while the test stimuli were electrical stimulation paradigms designed to evoke itch or pain. Pain was significantly reduced (CPM-effect) by the conditioning pain stimulus (p

  7. The role of fluoxetine on macrophage function in chronic pain (Experimental study in Balb/c mice

    Directory of Open Access Journals (Sweden)

    Dwi Pudjonarko

    2015-11-01

    Full Text Available Chronic pain raises stress conditions such as depression that can lower the cellular immunity. Fluoxetine is an antidepressant  used as an adjuvant in pain management but no one has been linked it with the body immune system. The objectives of this research were to proof the benefits of fluoxetine in  preventing degradation of macrophage function in chronic pain by measuring the macrophage phagocytic index , macrophage NO levels and the liver bacterial count in BALB/c mice infected with Listeria Monocytogenes.A Post Test - Only Control Group Design was conducted using 28 male mice strain BALB /c, age 8-10 weeks. The control group (C, mice got the same standard feed as the other groups. Chronic pain group (P, mice were injected with 20μL intraplantar CFA on day-1. Pain + fluoxetine early group (PFE were treated with P + fluoxetine 5 mg / kg ip day-1, the 4th, the 7th and the 10th, while the Pain + fluoxetine late group (PFL were treated with P + fluoxetine 5 mg / kg ip on day 7th and 10th. All mice were injected with 104 live Listeria monocytogenes iv on day 8th. Termination was performed on day 13th. Differences within groups  were analyzed using  One-way ANOVA and Kruskall Wallis, whereas the correlation of variables were analyzed using  Pearson's product moment. The experimental results showed that The macrophage phagocytic index and NO macrophage level (pg/mL in PFE group(2,24±1,013; 0,24±0,239 was higher than than P group (1,68±0,920; 0,21±0,263 and there was no different in the macrophage phagocytic index of PFE group compared to C group (p=0,583; p=0,805. In PFL group (4,32±1,459; 0,54±0,294 the macrophage phagocytic index as well as NO macrophage level (pg/mL was higher than P group (1,68±0,920; 0,21±0,263 with p=0,002; p=0,017. P group Bacterial count (log cfu/gram (2,30±0,849 was significantly higher than C group(1,15±0,223 (p=0,007, while PFE group bacterial count (1,96±0,653 and PFL group bacterial count (1,84±0

  8. Immunomodulation in human and experimental uveitis: Recent advances

    Directory of Open Access Journals (Sweden)

    Singh Vijay

    1999-01-01

    Full Text Available Experimental autoimmune uveitis (EAU is a T-cell mediated autoimmune disease that targets the neural retina and serves as a model of human uveitis. EAU can be induced against several retinal proteins in rats, mice, and subhuman primates. These include the S-antigen, a major protein in retinal photoreceptor cells; interphotoreceptor retinoid-binding protein (IRBP; and rhodopsin and other antigens of retinal origin. There are many similarities between clinical uveitis and EAU, but the latter differs in being self-limited, and needs adjuvant for disease induction. The experimental disease can be induced only in susceptible animal strains. Use of the EAU model has helped investigators understand the pathophysiology of the disease and to evaluate disease-modifying strategies, which could be applied in the clinic. There has been significant progress in this field during last decade, but much more understanding is needed before the knowledge can be transferred to clinical practice. A deeper understanding of the immune mechanisms involved in the EAU model may lead to the development of new therapeutic approaches targeted at various components of the immune response by immunomodulation to control uveitis. This review summarises the evidence from the EAU model, which could be of relevance to the clinical management of patients with uveitis.

  9. Mechano-sensitive nociceptors are required to detect heat pain thresholds and cowhage itch in human skin.

    Science.gov (United States)

    Weinkauf, B; Dusch, M; van der Ham, J; Benrath, J; Ringkamp, M; Schmelz, M; Rukwied, R

    2016-02-01

    Mechano-sensitive and mechano-insensitive C-nociceptors in human skin differ in receptive field sizes and electrical excitation thresholds, but their distinct functional roles are yet unclear. After blocking the lateral femoral cutaneous nerve (NCFL) in eight healthy male subjects (3-mL Naropin(®) 1%), we mapped the skin innervation territory being anaesthetic to mechanical pin prick but sensitive to painful transcutaneous electrical stimuli. Such 'differentially anaesthetic zones' indicated that the functional innervation with mechano-sensitive nociceptors was absent but the innervation with mechano-insensitive nociceptors remained intact. In these areas, we explored heat pain thresholds, low pH-induced pain, cowhage- and histamine-induced itch, and axon reflex flare. In differentially anaesthetic skin, heat pain thresholds were above the cut-off of 50°C (non-anaesthetized skin 47 ± 0.4°C). Pain ratings to 30 μL pH 4 injections were reduced compared to non-anaesthetized skin (48 ± 9 vs. 79 ± 6 VAS; p pain. The mechano-sensitive nociceptors are crucial for cowhage-induced itch and for the assessment of heat pain thresholds. © 2015 European Pain Federation - EFIC®

  10. Prolonged amelioration of experimental postoperative pain by bupivacaine released from microsphere-coated hernia mesh.

    Science.gov (United States)

    Ohri, Rachit; Wang, Jeffery Chi-Fei; Pham, Lan; Blaskovich, Phillip D; Costa, Daniel; Nichols, Gary; Hildebrand, William; Scarborough, Nelson; Herman, Clifford; Strichartz, Gary R

    2014-01-01

    Postoperative pain alters physiological functions and delays discharge. Perioperative local anesthetics are effective analgesics in the immediate 1- to 2-day postoperative period, but acute pain often lasts longer. The goal of this work was to develop a local anesthetic formulation adhering to an intraoperative implanted device that reduces pain for at least 3 days after surgery. Six groups, each with 8 rats, were studied. In a control group (group I), one 1.2-cm-long incision of the skin was followed by blunt dissection to separate the skin away from the underlying tissues and closing with 2 sutures. In 3 of the treatment groups, the same surgical procedure was used, with the subcutaneous space formed by the blunt dissection lined with a 1-cm square patch of hernia mesh coated with poly lactide co-glycolic acid microspheres containing approximately 17 mg of bupivacaine (group II), no drug (placebo; group III), or bupivacaine free-base powder (group IV). Uncoated mesh implants (group V) served as a secondary control. A standard bupivacaine solution (0.4 mL, 0.5%; 2-mg dose) was infiltrated subcutaneously 30 minutes before the surgery and served as a standard control (group VI). Mechanosensitivity of the skin was tested by the local subcutaneous muscle responses to cutaneous tactile stimulation by von Frey hairs with forces of 4 g (for allodynia) and 15 g (for hyperalgesia) preoperatively and for 7 postoperative days. Control rats (group I) showed mechanohypersensitivity, indicative of postoperative allodynia and hyperalgesia, for all 7 postoperative days. Mechanohyperalgesia in rats that received mesh coated with bupivacaine-releasing microspheres (group II) was reduced during this period to 13% of control postoperative values (P < 0.001); mesh coated with bupivacaine base (group IV) reduced it by 50% (P = 0.034). The placebo mesh (group III) and uncoated mesh (group V) caused no significant reduction of mechanohypersensitivity, and bupivacaine solution infiltrated

  11. The Effects of Sleep Deprivation on Pain

    OpenAIRE

    Kundermann, Bernd; Krieg, Jürgen-Christian; Schreiber, Wolfgang; Lautenbacher, Stefan

    2004-01-01

    Chronic pain syndromes are associated with alterations in sleep continuity and sleep architecture. One perspective of this relationship, which has not received much attention to date, is that disturbances of sleep affect pain. To fathom this direction of cause, experimental human and animal studies on the effects of sleep deprivation on pain processing were reviewed. According to the majority of the studies, sleep deprivation produces hyperalgesic changes. Furthermore, sleep deprivation can c...

  12. Participation of neuronal nitric oxide synthase in experimental neuropathic pain induced by sciatic nerve transection

    Directory of Open Access Journals (Sweden)

    M. Chacur

    2010-04-01

    Full Text Available Nerve injury leads to a neuropathic pain state that results from central sensitization. This phenomenom is mediated by NMDA receptors and may involve the production of nitric oxide (NO. In this study, we investigated the expression of the neuronal isoform of NO synthase (nNOS in the spinal cord of 3-month-old male, Wistar rats after sciatic nerve transection (SNT. Our attention was focused on the dorsal part of L3-L5 segments receiving sensory inputs from the sciatic nerve. SNT resulted in the development of neuropathic pain symptoms confirmed by evaluating mechanical hyperalgesia (Randall and Selitto test and allodynia (von Frey hair test. Control animals did not present any alteration (sham-animals. The selective inhibitor of nNOS, 7-nitroindazole (0.2 and 2 µg in 50 µL, blocked hyperalgesia and allodynia induced by SNT. Immunohistochemical analysis showed that nNOS was increased (48% by day 30 in the lumbar spinal cord after SNT. This increase was observed near the central canal (Rexed’s lamina X and also in lamina I-IV of the dorsal horn. Real-time PCR results indicated an increase of nNOS mRNA detected from 1 to 30 days after SNT, with the highest increase observed 1 day after injury (1469%. Immunoblotting confirmed the increase of nNOS in the spinal cord between 1 and 15 days post-lesion (20%, reaching the greatest increase (60% 30 days after surgery. The present findings demonstrate an increase of nNOS after peripheral nerve injury that may contribute to the increase of NO production observed after peripheral neuropathy.

  13. Experimental study of power generation utilizing human excreta

    International Nuclear Information System (INIS)

    Mudasar, Roshaan; Kim, Man-Hoe

    2017-01-01

    Highlights: • Power generation from human excreta has been studied under ambient conditions. • Biogas increases with solid wastes and continuous feeding at mesophilic conditions. • Understand the potential of human excreta for domestic power generating systems. • 26.8 kW h power is generated using biogas of 0.35 m 3 /kg from waste of 35 kg. • Continuous feeding produces 0.7 m 3 /kg biogas and generates 60 kW h power. - Abstract: This study presents the energetic performance of the biomass to produce power for micro scale domestic usage. Human excreta are chosen as the subject of the study to investigate their potential to produce biogas under ambient conditions. Furthermore, the research examines the approaches by which biogas production can be enhanced and purified, leading to a high-power generation system. The experimental work focuses on the design and fabrication of a biogas digester with a reverse solar reflector, water scrubbing tower, and a dryer. Anaerobic digestion has been considered as the decomposition method using solar energy which is a heat providing source. Specifically, two types of experiments have been performed, namely, feces to water weight proportion and continuous feeding experiments, each involving a set of six samples. The effect of parameters such as pH, ambient temperature, and biogas upgradation reveals that volume of biogas and power generation can be best obtained when an 8:2 feces to water weight sample is employed and when the feeding is applied every fifth day. In addition, this study discusses the environmental prospects of the biogas technology, which is achieved by using the water purification method to improve the methane percentage to 85% and remove undesired gases. The motivation behind this work is to understand the potential of human excreta for the development of domestic power generating systems. The results obtained reveal that 0.35 m 3 /kg of biogas is produced with 8:2 weight proportion sample, which

  14. Effect of family presence on pain and anxiety during invasive nursing procedures in an emergency department: A randomized controlled experimental study.

    Science.gov (United States)

    İşlekdemir, Burcu; Kaya, Nurten

    2016-01-01

    Patients generally prefer to have their family present during medical or nursing interventions. Family presence is assumed to reduce anxiety, especially during painful interventions. This study employed a randomized controlled experimental design to determine the effects of family presence on pain and anxiety during invasive nursing procedures. The study population consisted of patients hospitalized in the observation unit of the internal medicine section in the emergency department of a university hospital. The sample comprised 138 patients assigned into the experimental and control groups by drawing lots. The invasive nursing procedure was carried out in the presence of family members, for members of the experimental group, and without family members, for members of the control group. Thus, the effects of family presence on pain and anxiety during the administration of an invasive nursing procedure to patients were analyzed. The results showed that members of the experimental and control groups did not differ with respect to the pain and state anxiety scores during the intervention. Family presence does not influence the participants' pain and anxiety during an invasive nursing procedure. Thus, the decision regarding family presence during such procedures should be based on patient preference. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. The development of human factors experimental evaluation techniques -The development of human factors technologies-

    International Nuclear Information System (INIS)

    Sim, Bong Shick; Oh, In Seok; Cha, Kyeong Ho; Lee, Hyun Chul

    1994-04-01

    In the 2nd year of the research project for the development of human factors evaluation techniques, we first defined the experimental target systems by the comparison study of the advanced control rooms proposed by foreign countries in order to make the experiment feasible and realistic for the 10 experimental items selected in the first year of the project. Then we have decided to confine our research on the big board overview panel and operator workstations. Following the development of selection criteria for our research interest, we have identified the design variables which may influence the performance of the operator by the functional analysis. The experimental variables which will be used for the evaluation of the proposed items are then defined by the relational analysis between evaluation items and design variables and they are classified by the characteristics of the measurement data. The functional requirements of ITF are developed to accommodate the necessary functions for carrying out the 10 evaluation items. The functional requirements for each sub-system of ITF have been developed with the experimental paradigm of APTEA. Finally we have reviewed the compact nuclear simulator (CNS) at KAERI from the point of view of jyman factors guidelines/principles and proposed the two possible layouts for the experimental apparatus for the evaluation of display alternative and operational procedure. (Author)

  16. A comparison of the antinociceptive effects of xylazine, detomidine and romifidine on experimental pain in horses.

    Science.gov (United States)

    Moens, Yves; Lanz, Francisca; Doherr, Marcus G; Schatzmann, Urs

    2003-07-01

    To study the analgesic potency of the alpha2-agonist romifidine in the horse using both an electrical current and a mechanical pressure model for nociceptive threshold testing. In addition, a comparison was made with doses of detomidine and xylazine that produce equivalent degrees of sedation. Randomized, placebo-controlled, blinded cross-over study. Six adult Swiss warmblood horses, one mare and five geldings, weighing from 530 to 650 kg and aged 6-15 years. Nociceptive thresholds were measured using an electrical stimulus applied to the coronary band and using a pneumatically operated pin pressing on the cannon bone. Measurements were made immediately before and every 15 minutes for 2 hours after IV injection of the test substances. Lifting of the foot indicated the test end point. The three alpha2-agonists caused a temporary increase in nociceptive thresholds with a maximal effect within 15 minutes and a return to baseline levels within 1 hour. Using electrical current testing nociceptive thresholds were significantly different from placebo (mean +/- SD) for detomidine at 15 minutes (from control 5.8 +/- 0.9 to 23.3 +/- 3.9 mA, p = 0.0066) and 30 minutes (from control 6.6 +/- 1.1 to 18.8 +/- 3.3 mA, p = 0.0091). The difference was significant for romifidine at 15 minutes only (from control 5.8 +/- 0.9 to 18.7 +/- 3.8 mA, p = 0.0066). With mechanical pressure testing nociceptive thresholds were significantly different from control for detomidine at 15 minutes (from 3.2 +/- 0.2 to 6.2 +/- 0.5 N, p = 0.00076) and 30 minutes (from 3.2 +/- 0.7 to 5.7 +/- 0.8 N, p = 0.0167). The difference was significant for xylazine at 15 minutes (from control 3.2 +/- 0.2 to 5.6 +/- 0.7 N, p = 0.0079). At 15 minutes the order of magnitude of the measured antinociceptive effect was significantly different between the two pain tests for both romifidine and detomidine, but not for xylazine. For romifidine, the increase of mean thresholds compared to placebo was 4.0 +/- 1.3 times

  17. A review of morphine and morphine-6-glucuronide's pharmacokinetic-pharmacodynamic relationships in experimental and clinical pain

    DEFF Research Database (Denmark)

    Sverrisdóttir, Eva; Lund, Trine Meldgaard; Olesen, Anne Estrup

    2015-01-01

    Morphine is a widely used opioid for treatment of moderate to severe pain, but large interindividual variability in patient response and no clear guidance on how to optimise morphine dosage regimen complicates treatment strategy for clinicians. Population pharmacokinetic-pharmacodynamic models can...... a detailed overview of the published human population pharmacokinetic-pharmacodynamic studies for morphine analgesia in addition to basic drug disposition and pharmacological properties of morphine and its analgesic active metabolite, morphine-6-glucuronide, that may help identify future covariates....... Furthermore, based on simulations from key pharmacokinetic-pharmacodynamic models, the contribution of morphine-6-glucuronide to the analgesic response in patients with renal insufficiency was investigated. Simulations were also used to examine the impact of effect-site equilibration half-life on time course...

  18. An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain From Spinal Cord Injury and Disease.

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas D; Deutsch, Reena; Zhao, Holly; Prasad, Hannah; Phan, Amy

    2016-09-01

    Using 8-hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, most of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta 9-THC on 3 separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was used to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model showed a significant analgesic response for vaporized cannabis. When subjective and psychoactive side effects (eg, good drug effect, feeling high, etc) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all P analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord. A crossover, randomized, placebo-controlled human laboratory experiment involving administration of vaporized cannabis was performed in patients with neuropathic pain related to spinal cord injury and disease. This study supports consideration of future research that would include longer duration studies over weeks to months to evaluate the efficacy of medicinal cannabis in patients with central neuropathic pain. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  19. Proteomic Studies on Human and Experimental Cerebral Malaria

    KAUST Repository

    Moussa, Ehab

    2012-07-01

    Cerebral malaria (CM) is a severe neurological complication of malaria infection that results from interrelated pathologies. Despite extensive research efforts, the mechanism of the disease is not completely understood. Clinical studies, postmortem analysis, and animal models have been the main research arenas in CM. In this thesis, shotgun proteomics approach was used to further understand the pathology of human and experimental CM. The mechanism by which CM turns fatal is yet to be identified. A clinical proteomics study was conducted on pooled plasma samples from children with reversible or fatal CM from the Gambia. The results show that depletion of coagulation factors and increased levels of circulating proteasomes are associated with fatal pediatric CM. This data suggests that the ongoing coagulation during CM might be a disseminated intravascular coagulation state that eventually causes depletion of the coagulation factors leading to petechial hemorrhages. In addition, the mechanism(s) by which blood transfusion benefits CM in children was investigated. To that end, the concentration and multimerization pattern of von-willebrand factor, and the concentration of haptoglobin in the plasma of children with CM who received blood transfusions were measured. In addition to clinical studies, experimental cerebral malaria (ECM) in mice has been long used as a model for the disease. A shotgun proteomics workflow was optimized to identify the proteomic signature of the brain tissue of mice with ECM.Because of the utmost importance of membrane proteins in the pathology of the disease, sample fractionation and filter aided sample preparation were used to recover them. The proteomic signature of the brains of mice infected with P. berghei ANKA that developed neurological syndrome, mice infected with P. berghei NK56 that developed severe malaria but without neurological signs, and non-infected mice, were compared to identify CM specific proteins. Among the differentially

  20. Effect of static magnetic field on pain level and expression of P2X3 receptors in the trigeminal ganglion in mice following experimental tooth movement.

    Science.gov (United States)

    Zhu, Yafen; Wang, Shengguo; Long, Hu; Zhu, Jingyi; Jian, Fan; Ye, Niansong; Lai, Wenli

    2017-01-01

    Recent research has demonstrated that static magnetic fields (SMF) can generate an analgesic effect in different conditions. The present study explored effects of SMF on pain levels and expressions of P2X3 receptors in trigeminal ganglion (TG) in mice after experimental tooth movement (tooth movement induced by springs between teeth). Experiments were performed in male mice (body mass: 25-30 g) and divided into SMF + force group, force group, and no force group. Exposure time was over 22 h per day. Mouse Grimace Scale was used for evaluating orofacial pain levels during experimental tooth movement at 4 h and 1, 3, 7, and 14 days. Meanwhile, expression levels of P2X3 receptors in the TG were evaluated by immunohistochemistry and western blotting at same time points. We finally found that during experimental tooth movement, pain levels of mice peaked at 3 days, and then decreased. While pain levels of mice were reduced in the SMF environment at 4 h, 1 and 3 days, there was a significant difference at 1 and 3 days. Meanwhile, under the action of SMF, expression levels of P2X3 receptors in TG were significantly lower at 4 h, 3 and 7 days. These results suggest that SMF can reduce pain levels in mice, and down-regulate P2X3 receptors in TG. Bioelectromagnetics. 38:22-30, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Experimental research of radiogenic therapy on human melanoma

    International Nuclear Information System (INIS)

    Min Fengling; Chinese Academy of Sciences, Beijing; Zhang Hong; Li Wenjiang; Liu Bing; Zhou Qingming; Duan Xin; Zhou Guangming; Gao Qingxiang

    2006-01-01

    To investigate the effect of low dose irradiation on gene transfer efficiency and the effect of adenoviral-mediated exogenous P53 overexpression on radiosensitivity of radioresistant human melanoma cell line A375 with wild type p53, control vector, a replication deficient recombinant adenoviral vector containing a CMV promoter and green fluorescent protein (AdCMV-GFP), was used to transfect the A375 cells preirradiated with or without 1 Gy X-ray radiation. The transduction efficiency of GFP gene was determined with fluorescence microscope directly. A375 cells radiated by 1 Gy X-ray were transfected with a replication deficient recombinant adenoviral vector carrying human wild p53 were detected using flow cytometry (FCM) at different time after transfection. The radiosensitivity of A375 cells after p53 transduction was assayed by clonoy formation. The authors found that 1 Gy exposure increased the gene transfer efficiency of A375 cells. The expression of exogenous P53 was found to be 60% to 80% of transfected cells during the first three days after transduction and then declined continuously down to the control level on the day 10. The G1 cell cycle arrest was also observed after p53 gene transfer. A375 cells that were transfected with p53 showed higher sensitivity of X-ray-induced cell killing than those cells that either were transfected with the viral vector carrying a green fluorescent protein gene or were not transfected at all. Low dose ionizing radiation can improve gene transfer efficiency of A375 cells mediated by adenovirus vector. Althrough the overexpresion of exogenous P53 may not inhibit cell growth and induce apoptosis of melanoma cell line A375 in vitro, it made the tumor cells much sensitive to death by irradiation. the data suggested that p53 gene might be a potential gene for melanoma therapy and provide the experimental evidences to clinically using the combination of radiation with gene therapy on melanoma. Namely, there may be a reduction of

  2. No effect of experimental occlusal interferences on pressure pain thresholds of the masseter and temporalis muscles in healthy women

    NARCIS (Netherlands)

    Michelotti, A; Farella, M; Steenks, MH; Gallo, LM; Palla, S

    It has been suggested that occlusal interferences may lead to pain and tenderness of the masticatory muscles. Tender jaw muscles are more sensitive to pressure pain, as assessed by means of pressure algometry. We tested the effects of occlusal interferences on the pressure pain threshold of the jaw

  3. The Web-Based Osteoarthritis Management Resource My Joint Pain Improves Quality of Care: A Quasi-Experimental Study.

    Science.gov (United States)

    Umapathy, Hema; Bennell, Kim; Dickson, Chris; Dobson, Fiona; Fransen, Marlene; Jones, Graeme; Hunter, David J

    2015-07-07

    Despite the availability of evidence-based guidelines for conservative treatment of osteoarthritis (OA), management is often confined to the use of analgesics and waiting for eventual total joint replacement. This suggests a gap in knowledge for persons with OA regarding the many different treatments available to them. Our objective was to evaluate outcomes after usage of a Web-based resource called My Joint Pain that contains tailored, evidence-based information and tools aimed to improve self-management of OA on self-management and change in knowledge. A quasi-experimental design was used to evaluate the My Joint Pain website intervention over a 12-month period. The intervention provided participants with general and user-specific information, monthly assessments with validated instruments, and progress-tracking tools. A nationwide convenience sample of 195 participants with self-assessed hip and/or knee OA completed both baseline and 12-month questionnaires (users: n=104; nonusers: n=91). The primary outcome measure was the Health Evaluation Impact Questionnaire (heiQ) to evaluate 8 different domains (health-directed activity, positive and active engagement in life, emotional distress, self-monitoring and insight, constructive attitudes and approaches, skill and technique acquisition, social integration and support, health service navigation) and the secondary outcome measure was the 17-item Osteoarthritis Quality Indicator (OAQI) questionnaire to evaluate the change in appropriateness of care received by participants. Independent t tests were used to compare changes between groups for the heiQ and chi-square tests to identify changes within and between groups from baseline to 12 months for each OAQI item. Baseline demographics between groups were similar for gender (152/195, 77.9% female), age (mean 60, SD 9 years) and body mass index (mean 31.1, SD 6.8 kg/m(2)). With the exception of health service navigation, mean effect sizes from all other heiQ domains

  4. Calcitonin gene-related peptide and pain

    DEFF Research Database (Denmark)

    Schou, Wendy Sophie; Ashina, Sait; Amin, Faisal Mohammad

    2017-01-01

    and cerebrospinal fluid in subjects with musculoskeletal pain. A randomized clinical trial on monoclonal antibody, which selectively binds to and inhibits the activity of CGRP (galcanezumab) in patients with osteoarthritis knee pain, failed to demonstrate improvement of pain compared with placebo. No studies......BACKGROUND: Calcitonin gene-related peptide (CGRP) is widely distributed in nociceptive pathways in human peripheral and central nervous system and its receptors are also expressed in pain pathways. CGRP is involved in migraine pathophysiology but its role in non-headache pain has not been...... clarified. METHODS: We performed a systematic literature search on PubMed, Embase and ClinicalTrials.gov for articles on CGRP and non-headache pain covering human studies including experimental studies and randomized clinical trials. RESULTS: The literature search identified 375 citations of which 50...

  5. The impact of patients' gender, race, and age on health care professionals' pain management decisions: an online survey using virtual human technology.

    Science.gov (United States)

    Wandner, Laura D; Heft, Marc W; Lok, Benjamin C; Hirsh, Adam T; George, Steven Z; Horgas, Anne L; Atchison, James W; Torres, Calia A; Robinson, Michael E

    2014-05-01

    Previous literature indicates that biases exist in pain ratings. Healthcare professionals have been found to use patient demographic cues such as sex, race, and age when making decisions about pain treatment. However, there has been little research comparing healthcare professionals' (i.e., physicians and nurses) pain decision policies based on patient demographic cues. The current study used virtual human technology to examine the impact of patients' sex, race, and age on healthcare professionals' pain ratings. One hundred and ninety-three healthcare professionals (nurses and physicians) participated in this online study. Healthcare professionals assessed virtual human patients who were male and African American to be experiencing greater pain intensity and were more willing to administer opioid analgesics to them than to their demographic counterparts. Similarly, nurses were more willing to administer opioids make treatment decisions than physicians. There was also a significant virtual human-sex by healthcare professional interaction for pain assessment and treatment decisions. The sex difference (male>female) was greater for nurses than physicians. Results replicated findings of previous studies using virtual human patients to assess the effect of sex, race, and age in pain decision-making. In addition, healthcare professionals' pain ratings differed depending on healthcare profession. Nurses were more likely to rate pain higher and be more willing to administer opioid analgesics than were physicians. Healthcare professionals rated male and African American virtual human patients as having higher pain in most pain assessment and treatment domains compared to their demographic counterparts. Similarly the virtual human-sex difference ratings were more pronounced for nurses than physicians. Given the large number of patients seen throughout the healthcare professionals' careers, these pain practice biases have important public health implications. This study

  6. Penis pain

    Science.gov (United States)

    Pain - penis ... Bites, either human or insect Cancer of the penis Erection that does not go away (priapism) Genital herpes Infected hair follicles Infected prosthesis of the penis Infection under the foreskin of uncircumcised men ( balanitis ) ...

  7. Short-Term Sensorimotor Effects of Experimental Occlusal Interferences on the Wake-Time Masseter Muscle Activity of Females with Masticatory Muscle Pain.

    Science.gov (United States)

    Cioffi, Iacopo; Farella, Mauro; Festa, Paola; Martina, Roberto; Palla, Sandro; Michelotti, Ambrosina

    2015-01-01

    To investigate the effects of the application of an acute alteration of the occlusion (ie, interference) on the habitual masseter electromyographic (EMG) activity of females with temporomandibular disorders (TMD)-related muscular pain during wakefulness. Seven female volunteers with masticatory myofascial pain participated in a crossover randomized clinical trial. Gold foils were glued on an occlusal contact area (active occlusal interference, AI) or on the vestibular surface of the same molar (dummy interference, DI) and left for 8 days. The masseter electromyogram was recorded during wakefulness in the natural environment by portable recorders under interference-free, dummy-interference, and active-interference conditions. The number, amplitude, and duration of EMG signal fractions with amplitudes above 10% of the maximum voluntary contraction (activity periods, APs) were computed in all experimental conditions. Muscle pain, headache, and perceived stress were each assessed with a visual analog scale (VAS), and an algometer was used to assess masseter and temporalis pressure pain thresholds. Data were analyzed by means of analysis of variance. The frequency and duration of the recorded APs did not differ significantly between the experimental conditions (P>.05), but a small and significant reduction of the EMG mean amplitude of the APs occurred with AI (P.05). An active occlusal interference in female volunteers with masticatory muscle pain had little influence on the masseter EMG activity pattern during wakefulness and did not affect the pressure tenderness of the masseter and temporalis.

  8. Pain genes.

    Directory of Open Access Journals (Sweden)

    Tom Foulkes

    2008-07-01

    Full Text Available Pain, which afflicts up to 20% of the population at any time, provides both a massive therapeutic challenge and a route to understanding mechanisms in the nervous system. Specialised sensory neurons (nociceptors signal the existence of tissue damage to the central nervous system (CNS, where pain is represented in a complex matrix involving many CNS structures. Genetic approaches to investigating pain pathways using model organisms have identified the molecular nature of the transducers, regulatory mechanisms involved in changing neuronal activity, as well as the critical role of immune system cells in driving pain pathways. In man, mapping of human pain mutants as well as twin studies and association studies of altered pain behaviour have identified important regulators of the pain system. In turn, new drug targets for chronic pain treatment have been validated in transgenic mouse studies. Thus, genetic studies of pain pathways have complemented the traditional neuroscience approaches of electrophysiology and pharmacology to give us fresh insights into the molecular basis of pain perception.

  9. Electrical stimulation of the insular cortex as a novel target for the relief of refractory pain: An experimental approach in rodents.

    Science.gov (United States)

    Dimov, Luiz Fabio; Toniolo, Elaine Flamia; Alonso-Matielo, Heloísa; de Andrade, Daniel Ciampi; Garcia-Larrea, Luis; Ballester, Gerson; Teixeira, Manoel Jacobsen; Dale, Camila Squarzoni

    2018-07-02

    Cortical electrical stimulation (CES) has shown to be an effective therapeutic alternative for neuropathic pain refractory to pharmacological treatment. The primary motor cortex(M1) was the main cortical target used in the vast majority of both invasive and non-invasive studies. Despite positive results M1-based approaches still fail to relieve pain in a significant proportion of individuals. It has been advocated that the direct stimulation of cortical areas directly implicated in the central integration of pain could increase the efficacy of analgesic brain stimulation. Here, we evaluated the behavioral effects of electrical stimulation of the insular cortex (ESI) on pain sensitivity in an experimental rat model of peripheral neuropathy, and have described the pathways involved. Animals underwent chronic constriction of the sciatic nerve in the right hind limb and had concentric electrodes implanted in the posterior dysranular insular cortex. Mechanical nociception responses were evaluated before and at the end of a 15-min session of ESI (60Hz, 210μs, 1V). ESI reversed mechanical hypersensitivity in the paw contralateral to the brain hemisphere stimulated, without inducing motor impairment in the open-field test. Pharmacological blockade of μ-opioid (MOR) or type 1-cannabinoid receptors (CB1R) abolished ESI-induced antinociceptive effects. Evaluation of CB1R and MOR spatial expression demonstrated differential modulation of CB1R and MOR in the periaqueductal gray matter (PAG) of ESI-treated rats in sub-areas involved in pain processing/modulation. These results indicate that ESI induces antinociception by functionally modulating opioid and cannabinoid systems in the PAG pain circuitry in rats with experimentally induced neuropathic pain. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. An experimental examination of catastrophizing-related interpretation bias for ambiguous facial expressions of pain using an incidental learning task

    Directory of Open Access Journals (Sweden)

    Ali eKHATIBI

    2014-09-01

    Full Text Available Individuals with pain-related concerns are likely to interpret ambiguous pain-related information in a threatening manner. It is unknown whether this interpretation bias also occurs for ambiguous pain-related facial expressions. This study examined whether individuals who habitually attach a catastrophic meaning to pain are characterized by negative interpretation bias for ambiguous pain-related facial expressions. Sixty-four female undergraduates completed an incidental learning task during which pictures of faces were presented, each followed by a visual target at one of two locations. Participants indicated target location by pressing one of two response keys. During the learning phase, happy and painful facial expressions predicted target location. During two test phases, morphed facial expressions of pain and happiness were added, equally often followed by a target at either location. Faster responses following morphs to targets at the location predicted by painful expressions compared to targets at the location predicted by happy expressions were taken to reflect pain-related interpretation bias. During one test phase, faces were preceded by either a safe or threatening context cue. High, but not low, pain-catastrophizers responded faster following morphs to targets at the location predicted by painful expressions than to targets at the other location (when participants were aware of the contingency between expression type and target location. When context cues were presented, there was no indication of interpretation bias. Participants were also asked to directly classify the facial expressions that were presented during the incidental learning task. Participants classified morphs more often as happy than as painful, independent of their level of pain catastrophizing. This observation is discussed in terms of differences between indirect and direct measures of interpretation bias.

  11. Investigation into the effects of using two or four acupuncture needles with bidirectional rotation on experimentally-induced contact heat pain in healthy subjects.

    Science.gov (United States)

    Paley, Carole A; Johnson, Mark I

    2015-02-01

    There is growing evidence from experimental studies that the acupuncture dose or technique influences the speed of onset of hypoalgesia. The aim of this study was to investigate the effects of acupuncture using two or four needles on experimental contact thermal pain in healthy volunteers. Forty two participants were randomised into three groups: four-needle group (LI4, LI11, LI10, TE5), two-needle group (verum at LI4, LI11 and mock at LI10, TE5) and mock acupuncture group (LI4, LI11, LI10, TE5). Each participant rated pain intensity (visual analogue scale, VAS) to a series of noxious stimuli administered to the forearm 2°C above the heat pain threshold during needling and immediately after removal of the needles. Experimentally-induced heat pain intensity (VAS) during and after the intervention was lower than pre-intervention but there were no statistically significant differences in this change between groups. There were no statistically significant differences between groups in the time taken for pain intensity to decrease by 33% from pre-intervention. However, a 33% decrease in pain intensity within 3 min of needle insertion was observed for 13 participants (92.9%) in the four-needle group compared with 66.7% of participants in the two-needle group and 57.1% in the mock acupuncture group. There was less variance in VAS in the four-needle group, suggesting more consistency in hypoalgesic response when using more needles. There is tentative evidence that four needles may be superior to two needles in generating rapid onset hypoalgesia. The findings suggest that further investigation is warranted. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  12. Genome-wide analysis of pain-, nerve- and neurotrophin -related gene expression in the degenerating human annulus

    Science.gov (United States)

    2012-01-01

    Background In spite of its high clinical relevance, the relationship between disc degeneration and low back pain is still not well understood. Recent studies have shown that genome-wide gene expression studies utilizing ontology searches provide an efficient and valuable methodology for identification of clinically relevant genes. Here we use this approach in analysis of pain-, nerve-, and neurotrophin-related gene expression patterns in specimens of human disc tissue. Control, non-herniated clinical, and herniated clinical specimens of human annulus tissue were studied following Institutional Review Board approval. Results Analyses were performed on more generated (Thompson grade IV and V) discs vs. less degenerated discs (grades I-III), on surgically operated discs vs. control discs, and on herniated vs. control discs. Analyses of more degenerated vs. less degenerated discs identified significant upregulation of well-recognized pain-related genes (bradykinin receptor B1, calcitonin gene-related peptide and catechol-0-methyltransferase). Nerve growth factor was significantly upregulated in surgical vs. control and in herniated vs. control discs. All three analyses also found significant changes in numerous proinflammatory cytokine- and chemokine-related genes. Nerve, neurotrophin and pain-ontology searches identified many matrix, signaling and functional genes which have known importance in the disc. Immunohistochemistry was utilized to confirm the presence of calcitonin gene-related peptide, catechol-0-methyltransferase and bradykinin receptor B1 at the protein level in the human annulus. Conclusions Findings point to the utility of microarray analyses in identification of pain-, neurotrophin and nerve-related genes in the disc, and point to the importance of future work exploring functional interactions between nerve and disc cells in vitro and in vivo. Nerve, pain and neurotrophin ontology searches identified numerous changes in proinflammatory cytokines and

  13. Morphine- and buprenorphine-induced analgesia and antihyperalgesia in a human inflammatory pain model

    DEFF Research Database (Denmark)

    Ravn, Pernille; Secher, EL; Skram, U

    2013-01-01

    Opioid therapy is associated with the development of tolerance and paradoxically increased sensitivity to pain. It has been suggested that buprenorphine is associated with a higher antihyperalgesia/analgesia ratio than μ-opioid receptor agonists. The primary outcome of this study was therefore...... to investigate relative differences in antihyperalgesia and analgesia effects between morphine and buprenorphine in an inflammatory pain model in volunteers. The secondary outcome was to examine the relationship between pain sensitivity and opioid-induced effects on analgesia, antihyperalgesia, and descending...... pain modulation....

  14. An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain from Spinal Cord Injury and Disease

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Zhao, Holly; Prasad, Hannah; Phan, Amy

    2016-01-01

    Using eight hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, the majority of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta-9-tetrahydrocannabinol on three separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was utilized to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model demonstrated a significant analgesic response for vaporized cannabis. When subjective and psychoactive side effects (e.g., good drug effect, feeling high, etc.) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all p<0.0004). Psychoactive and subjective effects were dose dependent. Measurement of neuropsychological performance proved challenging because of various disabilities in the population studied. As the two active doses did not significantly differ from each other in terms of analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord. PMID:27286745

  15. Filtering the reality: functional dissociation of lateral and medial pain systems during sleep in humans.

    Science.gov (United States)

    Bastuji, Hélène; Mazza, Stéphanie; Perchet, Caroline; Frot, Maud; Mauguière, François; Magnin, Michel; Garcia-Larrea, Luis

    2012-11-01

    Behavioral reactions to sensory stimuli during sleep are scarce despite preservation of sizeable cortical responses. To further understand such dissociation, we recorded intracortical field potentials to painful laser pulses in humans during waking and all-night sleep. Recordings were obtained from the three cortical structures receiving 95% of the spinothalamic cortical input in primates, namely the parietal operculum, posterior insula, and mid-anterior cingulate cortex. The dynamics of responses during sleep differed among cortical sites. In sleep Stage 2, evoked potential amplitudes were similarly attenuated relative to waking in all three cortical regions. During paradoxical, or rapid eye movements (REM), sleep, opercular and insular potentials remained stable in comparison with Stage 2, whereas the responses from mid-anterior cingulate abated drastically, and decreasing below background noise in half of the subjects. Thus, while the lateral operculo-insular system subserving sensory analysis of somatic stimuli remained active during paradoxical-REM sleep, mid-anterior cingulate processes related to orienting and avoidance behavior were suppressed. Dissociation between sensory and orienting-motor networks might explain why nociceptive stimuli can be either neglected or incorporated into dreams without awakening the subject. Copyright © 2011 Wiley Periodicals, Inc.

  16. Experimental integrative muscular movement technique enhances cervical range of motion in patients with chronic neck pain: a pilot study.

    Science.gov (United States)

    Rohe, Benjamin G; Carter, Ronald; Thompson, William R; Duncan, Randall L; Cooper, Carlton R

    2015-04-01

    Neck pain presents a tremendous physical and financial burden. This study compared the efficacy of the complementary and alternative medical treatments of integrative muscular movement technique (IMMT) and Swedish massage on neck pain in women of occupation age, the largest demographic group with neck pain. A total of 38 women were assigned to IMMT (n=28) or Swedish massage (n=10) in a blinded manner. Both groups received eight 30-minute treatments over 4 weeks. Cervical range of motion (ROM) in flexion, extension, sidebending, and rotation was measured before and after treatment. Each patient's pain was assessed by using an analogue pain scale of 0-10. Compared with the Swedish massage group, patients receiving IMMT experienced a significant increase in ROM in cervical flexion (ppain for IMMT was -1.75 units compared with -0.3 units for Swedish massage (pcervical ROM in every movement measured compared with Swedish massage. Inclusion of the IMMT in a treatment regimen for chronic neck pain may lead to decreased pain and increased cervical ROM. These positive effects of the IMMT intervention may have a role in enhancing functional outcomes in patients with neck pain.

  17. Sodium channel Nav1.7 immunoreactivity in painful human dental pulp and burning mouth syndrome

    Directory of Open Access Journals (Sweden)

    Yiangou Yiangos

    2010-06-01

    Full Text Available Abstract Background Voltage gated sodium channels Nav1.7 are involved in nociceptor nerve action potentials and are known to affect pain sensitivity in clinical genetic disorders. Aims and Objectives To study Nav1.7 levels in dental pulpitis pain, an inflammatory condition, and burning mouth syndrome (BMS, considered a neuropathic orofacial pain disorder. Methods Two groups of patients were recruited for this study. One group consisted of patients with dental pulpitis pain (n = 5 and controls (n = 12, and the other patients with BMS (n = 7 and controls (n = 10. BMS patients were diagnosed according to the International Association for the Study of Pain criteria; a pain history was collected, including the visual analogue scale (VAS. Immunohistochemistry with visual intensity and computer image analysis were used to evaluate levels of Nav1.7 in dental pulp tissue samples from the dental pulpitis group, and tongue biopsies from the BMS group. Results There was a significantly increased visual intensity score for Nav1.7 in nerve fibres in the painful dental pulp specimens, compared to controls. Image analysis showed a trend for an increase of the Nav1.7 immunoreactive % area in the painful pulp group, but this was not statistically significant. When expressed as a ratio of the neurofilament % area, there was a strong trend for an increase of Nav1.7 in the painful pulp group. Nav1.7 immunoreactive fibres were seen in abundance in the sub-mucosal layer of tongue biopsies, with no significant difference between BMS and controls. Conclusion Nav1.7 sodium channel may play a significant role in inflammatory dental pain. Clinical trials with selective Nav1.7 channel blockers should prioritise dental pulp pain rather than BMS.

  18. Sodium channel Nav1.7 immunoreactivity in painful human dental pulp and burning mouth syndrome

    Science.gov (United States)

    2010-01-01

    Background Voltage gated sodium channels Nav1.7 are involved in nociceptor nerve action potentials and are known to affect pain sensitivity in clinical genetic disorders. Aims and Objectives To study Nav1.7 levels in dental pulpitis pain, an inflammatory condition, and burning mouth syndrome (BMS), considered a neuropathic orofacial pain disorder. Methods Two groups of patients were recruited for this study. One group consisted of patients with dental pulpitis pain (n = 5) and controls (n = 12), and the other patients with BMS (n = 7) and controls (n = 10). BMS patients were diagnosed according to the International Association for the Study of Pain criteria; a pain history was collected, including the visual analogue scale (VAS). Immunohistochemistry with visual intensity and computer image analysis were used to evaluate levels of Nav1.7 in dental pulp tissue samples from the dental pulpitis group, and tongue biopsies from the BMS group. Results There was a significantly increased visual intensity score for Nav1.7 in nerve fibres in the painful dental pulp specimens, compared to controls. Image analysis showed a trend for an increase of the Nav1.7 immunoreactive % area in the painful pulp group, but this was not statistically significant. When expressed as a ratio of the neurofilament % area, there was a strong trend for an increase of Nav1.7 in the painful pulp group. Nav1.7 immunoreactive fibres were seen in abundance in the sub-mucosal layer of tongue biopsies, with no significant difference between BMS and controls. Conclusion Nav1.7 sodium channel may play a significant role in inflammatory dental pain. Clinical trials with selective Nav1.7 channel blockers should prioritise dental pulp pain rather than BMS. PMID:20529324

  19. Intramuscular temperature modulates glutamate-evoked masseter muscle pain intensity in humans.

    Science.gov (United States)

    Sato, Hitoshi; Castrillon, Eduardo E; Cairns, Brian E; Bendixen, Karina H; Wang, Kelun; Nakagawa, Taneaki; Wajima, Koichi; Svensson, Peter

    2015-01-01

    To determine whether glutamate-evoked jaw muscle pain is altered by the temperature of the solution injected. Sixteen healthy volunteers participated and received injections of hot (48°C), neutral (36°C), or cold (3°C) solutions (0.5 mL) of glutamate or isotonic saline into the masseter muscle. Pain intensity was assessed with an electronic visual analog scale (eVAS). Numeric rating scale (NRS) scores of unpleasantness and temperature perception, pain-drawing areas, and pressure pain thresholds (PPTs) were also measured. Participants filled out the McGill Pain Questionnaire (MPQ). Two-way or three-way repeated measures ANOVA were used for data analyses. Injection of hot glutamate and cold glutamate solutions significantly increased and decreased, respectively, the peak pain intensity compared with injection of neutral glutamate solution. The duration of glutamate-evoked pain was significantly longer when hot glutamate was injected than when cold glutamate was injected. No significant effect of temperature on pain intensity was observed when isotonic saline was injected. No effect of solution temperature was detected on unpleasantness, heat perception, cold perception, area of pain drawings, or PPTs. There was a significantly greater use of the "numb" term in the MPQ to describe the injection of cold solutions compared to the injection of both neutral and hot solutions. Glutamate-evoked jaw muscle pain was significantly altered by the temperature of the injection solution. Although temperature perception in the jaw muscle is poor, pain intensity is increased when the muscle tissue temperature is elevated.

  20. Social interaction and pain: An arctic expedition.

    Science.gov (United States)

    Block, Per; Heathcote, Lauren C; Burnett Heyes, Stephanie

    2018-01-01

    Complex human behaviour can only be understood within its social environment. However, disentangling the causal links between individual outcomes and social network position is empirically challenging. We present a research design in a closed real-world setting with high-resolution temporal data to understand this interplay within a fundamental human experience - physical pain. Study participants completed an isolated 3-week hiking expedition in the Arctic Circle during which they were subject to the same variation in environmental conditions and only interacted amongst themselves. Adolescents provided daily ratings of pain and social interaction partners. Using longitudinal network models, we analyze the interplay between social network position and the experience of pain. Specifically, we test whether experiencing pain is linked to decreasing popularity (increasing isolation), whether adolescents prefer to interact with others experiencing similar pain (homophily), and whether participants are increasingly likely to report similar pain as their interaction partners (contagion). We find that reporting pain is associated with decreasing popularity - interestingly, this effect holds for males only. Further exploratory analyses suggest this is at least partly driven by males withdrawing from contact with females when in pain, enhancing our understanding of pain and masculinity. Contrary to recent experimental and clinical studies, we found no evidence of pain homophily or contagion in the expedition group. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. No effect of experimental occlusal interferences on pressure pain thresholds of the masseter and temporalis muscles in healthy women.

    Science.gov (United States)

    Michelotti, A; Farella, M; Steenks, M H; Gallo, L M; Palla, S

    2006-04-01

    It has been suggested that occlusal interferences may lead to pain and tenderness of the masticatory muscles. Tender jaw muscles are more sensitive to pressure pain, as assessed by means of pressure algometry. We tested the effects of occlusal interferences on the pressure pain threshold of the jaw muscles by means of a double-blind randomized crossover experiment carried out on 11 young healthy females. Golden strips were glued either to an occlusal contact area (active interference) or to the vestibular surface of the same tooth (dummy interference) and left for 8 d each. Pressure pain thresholds of the masseter and anterior temporalis muscles were assessed under interference-free, dummy-interference and active-interference conditions. The results indicated that the application of an active occlusal interference, as used in this study, did not influence significantly the pressure pain thresholds of these muscles in healthy individuals.

  2. Ultrasound evidence of altered lumbar connective tissue structure in human subjects with chronic low back pain

    Directory of Open Access Journals (Sweden)

    Bouffard Nicole A

    2009-12-01

    Full Text Available Abstract Background Although the connective tissues forming the fascial planes of the back have been hypothesized to play a role in the pathogenesis of chronic low back pain (LBP, there have been no previous studies quantitatively evaluating connective tissue structure in this condition. The goal of this study was to perform an ultrasound-based comparison of perimuscular connective tissue structure in the lumbar region in a group of human subjects with chronic or recurrent LBP for more than 12 months, compared with a group of subjects without LBP. Methods In each of 107 human subjects (60 with LBP and 47 without LBP, parasagittal ultrasound images were acquired bilaterally centered on a point 2 cm lateral to the midpoint of the L2-3 interspinous ligament. The outcome measures based on these images were subcutaneous and perimuscular connective tissue thickness and echogenicity measured by ultrasound. Results There were no significant differences in age, sex, body mass index (BMI or activity levels between LBP and No-LBP groups. Perimuscular thickness and echogenicity were not correlated with age but were positively correlated with BMI. The LBP group had ~25% greater perimuscular thickness and echogenicity compared with the No-LBP group (ANCOVA adjusted for BMI, p Conclusion This is the first report of abnormal connective tissue structure in the lumbar region in a group of subjects with chronic or recurrent LBP. This finding was not attributable to differences in age, sex, BMI or activity level between groups. Possible causes include genetic factors, abnormal movement patterns and chronic inflammation.

  3. [Experimental study on human periodontal ligament cells transfected with human amelogenin gene].

    Science.gov (United States)

    Yu, Guang; Shu, Rong; Sun, Ying; Cheng, Lan; Song, Zhong-Chen; Zhang, Xiu-Li

    2008-02-01

    To construct the recombinant lentiviral vector of human amelogenin gene, infect human periodontal ligament cells with the recombinant lentivirus, and evaluate the feasibility of applying modified PDLCs as seeds for a further periodontal reconstruction. The mature peptide of hAm cDNA was cloned and linked into the vector plasmid, the recombinant plasmid FUAmW was confirmed by double enzyme digestion and sequence analysis. Recombinant lentivirus was prepared from 293T cells by polytheylenimine (PEI)-mediated transient cotransfection. The hPDLCs and 293T cells were infected with the generated lentivirus. The infection efficiency was analysed by detection of green fluorescence protein (GFP) with fluorescent microscope and flow cytometer 72 hours later. The expression of hAm gene was detected by reverse transcription polymerase chain reaction (RT-PCR). The sequence of inserted fragment in recombinant plasmid was identical to the hAm sequence reported in Genebank. Green fluorescence was visible under fluorescent microscope, FCM assay showed that positive percentage was 69.46% and 33.99% in 293T and hPDLCs, respectively. The targeted gene was obtained in the experimental groups by RT-PCR. The recombinan lentiviral vector of hAm gene is constructed successfully and it could be transfected into cultured hPDLCs. hAm gene and seed cells may be used for further study in the fields periodontal tissue engineering. Supported by National Natural Science Foundation of China (Grant No. 30672315).

  4. Experimental Gene Therapy with Serine-Histogranin and Endomorphin 1 for the Treatment of Chronic Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Stanislava Jergova

    2017-12-01

    Full Text Available The insufficient pain relief provided by current pharmacotherapy for chronic neuropathic pain is a serious medical problem. The enhanced glutamate signaling via NMDA receptors appears to be one of the key events in the development of chronic pain. Although effective, clinical use of systemic NMDA antagonists is limited by adverse effects such as hallucinations and motor dysfunction. Opioids are also potent analgesics but their chronic use is accompanied by tolerance and risk of addiction. However, combination of NMDA antagonists and opioids seems to provide a stable pain relieve at subthreshold doses of both substances, eliminating development of side effects. Our previous research showed that combined delivery of NMDA antagonist Serine histrogranin (SHG and endomorphin1 (EM1 leads to attenuation of acute and chronic pain. The aim of this study was to design and evaluate an analgesic potency of the gene construct encoding SHG and EM1. Constructs with 1SHG copy in combination with EM1, 1SHG/EM1, and 6SHG/EM1 were intraspinally injected to animals with peripheral nerve injury-induced pain (chronic constriction injury, CCI or spinal cord injury induced pain (clip compression model, SCI and tactile and cold allodynia were evaluated. AAV2/8 particles were used for gene delivery. The results demonstrated 6SHG/EM1 as the most efficient for alleviation of pain-related behavior. The effect was observed up to 8 weeks in SCI animals, suggesting the lack of tolerance of possible synergistic effect between SHG and EM1. Intrathecal injection of SHG antibody or naloxone attenuated the analgesic effect in treated animals. Biochemical and histochemical evaluation confirmed the presence of both peptides in the spinal tissue. The results of this study showed that the injection of AAV vectors encoding combined SHG/EM constructs can provide long term attenuation of pain without overt adverse side effects. This approach may provide better treatment options for

  5. The effects of patient-professional partnerships on the self-management and health outcomes for patients with chronic back pain: A quasi-experimental study.

    Science.gov (United States)

    Fu, Yu; Yu, Ge; McNichol, Elaine; Marczewski, Kathryn; José Closs, S

    2016-07-01

    Self-management may be a lifelong task for patients with chronic back pain. Research suggests that chronic pain self-management programmes have beneficial effects on patients' health outcome. Contemporary pain management theories and models also suggest that a good patient-professional partnership enhances patients' ability to self-manage their condition. (1) To investigate whether there is a reciprocal relationship between self-management of chronic back pain and health-related quality of life (HRQoL); (2) to examine the impact of a good patient-professional partnership on HRQoL, either directly, or indirectly via change in the ability to self-manage pain. This quasi-experimental study was designed to take place during routine service appointments and conducted in a community-based pain management service in the United Kingdom. A patient-professional partnership was established in which patients were actively involved in setting up goals and developing individualised care plans. Through this, health professionals undertook patients' health needs assessment, collaborated with patients to identify specific problems, provided written materials and delivered individualised exercise based on patients' life situation. Patients were recruited following initial consultation and followed up three months later. A total of 147 patients (65% female) with a mean age of 48 years (standard deviation (SD): 14 years) were enrolled in the study. Of these, 103 subjects completed the study. Patients were included if they were aged 18 and over, suffered from chronic back pain, had opted in to the clinic and had sufficient ability to read and understand English. Patients were excluded if they opted out this service after the initial assessment, suffered from malignant pain or required acute medical interventions for their pain relief. Self-reported measures of HRQoL, patient-professional partnerships and self-management ability were collected at baseline and three months later

  6. Neurosensory changes in a human model of endothelin-1 induced pain: a behavioral study

    NARCIS (Netherlands)

    Hans, Guy; Deseure, Kristof; Robert, Dominique; de Hert, Stefan

    2007-01-01

    Although pain is a frequent feature in patients with cancer, its etiology is still poorly understood. In recent years, endothelin-1 (ET-1) has become a major target molecule in the etiology of cancer pain. In this randomised, double-blind study the effects of intradermal injection of ET-1 on

  7. Genetic and environmental factors in experimental and human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Takayama, S.; Takebe, H.; Gelboin, H.V.; MaChahon, B.; Matsushima, T.; Sugimura, T.

    1980-01-01

    Recently technological advances in assaying mutagenic principles have revealed that there are many mutagens in the environment, some of which might be carcinogenic to human beings. Other advances in genetics have shown that genetic factors might play an important role in the induction of cancer in human beings, e.g., the high incidence of skin cancers in patients with xeroderma pigmentosum. These proceedings deal with the relationships between genetic and environmental factors in carcinogenesis. The contributors cover mixed-function oxidases, pharmacogenetics, twin studies, DNA repair, immunology, and epidemiology.

  8. Relationships between craniofacial pain and bruxism.

    Science.gov (United States)

    Svensson, P; Jadidi, F; Arima, T; Baad-Hansen, L; Sessle, B J

    2008-07-01

    A still commonly held view in the literature and clinical practice is that bruxism causes pain because of overloading of the musculoskeletal tissue and craniofacial pain, on the other hand, triggers more bruxism. Furthermore, it is often believed that there is a dose-response gradient so that more bruxism (intensity, duration) leads to more overloading and pain. Provided the existence of efficient techniques to treat bruxism, it would be straightforward in such a simple system to target bruxism as the cause of pain and hence treat the pain. Of course, human biological systems are much more complex and therefore, it is no surprise that the relationship between bruxism and pain is far from being simple or even linear. Indeed, there are unexpected relationships, which complicate the establishment of adequate explanatory models. Part of the reason is the complexity of the bruxism in itself, which presents significant challenges related to operationalized criteria and diagnostic tools and underlying pathophysiology issues, which have been dealt with in other reviews in this issue. However, another important reason is the multifaceted nature of craniofacial pain. This review will address our current understanding of classification issues, epidemiology and neurobiological mechanisms of craniofacial pain. Experimental models of bruxism may help to further the understanding of the relationship between craniofacial pain and bruxism in addition to insights from intervention studies. The review will enable clinicians to understand the reasons why simple cause-effect relationships between bruxism and craniofacial pain are inadequate and the current implications for management of craniofacial pain.

  9. Physics of human cooperation: experimental evidence and theoretical models

    Science.gov (United States)

    Sánchez, Angel

    2018-02-01

    In recent years, many physicists have used evolutionary game theory combined with a complex systems perspective in an attempt to understand social phenomena and challenges. Prominent among such phenomena is the issue of the emergence and sustainability of cooperation in a networked world of selfish or self-focused individuals. The vast majority of research done by physicists on these questions is theoretical, and is almost always posed in terms of agent-based models. Unfortunately, more often than not such models ignore a number of facts that are well established experimentally, and are thus rendered irrelevant to actual social applications. I here summarize some of the facts that any realistic model should incorporate and take into account, discuss important aspects underlying the relation between theory and experiments, and discuss future directions for research based on the available experimental knowledge.

  10. Pain sensation in human osteoarthritic knee joints is strongly enhanced by diabetes mellitus.

    Science.gov (United States)

    Eitner, Annett; Pester, Julia; Vogel, Franziska; Marintschev, Ivan; Lehmann, Thomas; Hofmann, Gunther O; Schaible, Hans-Georg

    2017-09-01

    The major burden of knee joint osteoarthritis (OA) is pain. Since in elder patients diabetes mellitus is an important comorbidity of OA, we explored whether the presence of diabetes mellitus has a significant influence on pain intensity at the end stage of knee OA, and we aimed to identify factors possibly related to changes of pain intensity in diabetic patients. In 23 diabetic and 47 nondiabetic patients with OA undergoing total knee arthroplasty, we assessed the pain intensity before the operation using the "Knee Injury and Osteoarthritis Outcome Score". Furthermore, synovial tissue, synovial fluid (SF), cartilage, and blood were obtained. We determined the synovitis score, the concentrations of prostaglandin E2 and interleukin-6 (IL-6) in the SF and serum, and of C-reactive protein and HbA1c and other metabolic parameters in the serum. We performed multivariate regression analyses to study the association of pain with several parameters. Diabetic patients had on average a higher Knee Injury and Osteoarthritis Outcome Score pain score than nondiabetic patients (P Knee joints from diabetic patients exhibited on average higher synovitis scores (P = 0.024) and higher concentrations of IL-6 in the SF (P = 0.003) than knee joints from nondiabetic patients. Multivariate regression analysis showed that patients with higher synovitis scores had more intense pain independent of all investigated confounders, and that the positive association between pain intensities and IL-6 levels was dependent on diabetes mellitus and/or synovitis. These data suggest that diabetes mellitus significantly increases pain intensity of knee OA, and that in diabetic patients higher pain intensities were determined by stronger synovitis.

  11. An Experimental Study of the Emergence of Human Communication Systems

    Science.gov (United States)

    Galantucci, Bruno

    2005-01-01

    The emergence of human communication systems is typically investigated via 2 approaches with complementary strengths and weaknesses: naturalistic studies and computer simulations. This study was conducted with a method that combines these approaches. Pairs of participants played video games requiring communication. Members of a pair were…

  12. Use of localized human growth hormone and testosterone injections in addition to manual therapy and exercise for lower back pain: a case series with 12-month follow-up

    Directory of Open Access Journals (Sweden)

    Dubick MN

    2015-06-01

    Full Text Available Marc N Dubick,1 Thomas H Ravin,2 Yvonne Michel,3 David C Morrisette4 1Interventional Pain Management, Division of Anesthesiology, Bon Secours St Francis Hospital, Charleston, SC, USA; 2Musculoskeletal Medicine, Val d'Isere Health Clinic, Denver, CO, USA; 3Statistical Consultant, Private Practice, Daniel Island, SC, USA; 4Division of Physical Therapy, Medical University of South Carolina, SC, USA Objective: The objective of this case series was to investigate the feasibility and safety of a novel method for the management of chronic lower back pain. Injections of recombinant human growth hormone and testosterone to the painful and dysfunctional areas in individuals with chronic lower back pain were used. In addition, the participants received manual therapies and exercise addressing physical impairments such as motor control, strength, endurance, pain, and loss of movement. Pain ratings and self-rated functional outcomes were assessed.Study design: This is a case series involving consecutive patients with chronic lower back pain who received the intervention of injections of recombinant human growth hormone and testosterone, and attended chiropractic and/or physical therapy. Outcomes were measured at 12 months from the time of injection.Setting: A community based hospital affiliated office, and a private practice block suite.Participants: A total of 60 consecutive patients attending a pain management practice for chronic lower back pain were recruited for the experimental treatment. Most participants were private pay.Interventions: Participants who provided informed consent and were determined not to have radicular pain received diagnostic blocks. Those who responded favorably to the diagnostic blocks received injections of recombinant human growth hormone and testosterone in the areas treated with the blocks. Participants also received manipulation- and impairment-based exercises.Outcome measures: Outcomes were assessed at 12 months through pain

  13. The effect of deep and slow breathing on pain perception, autonomic activity, and mood processing--an experimental study.

    Science.gov (United States)

    Busch, Volker; Magerl, Walter; Kern, Uwe; Haas, Joachim; Hajak, Göran; Eichhammer, Peter

    2012-02-01

    Deep and slow breathing (DSB) techniques, as a component of various relaxation techniques, have been reported as complementary approaches in the treatment of chronic pain syndromes, but the relevance of relaxation for alleviating pain during a breathing intervention was not evaluated so far. In order to disentangle the effects of relaxation and respiration, we investigated two different DSB techniques at the same respiration rates and depths on pain perception, autonomic activity, and mood in 16 healthy subjects. In the attentive DSB intervention, subjects were asked to breathe guided by a respiratory feedback task requiring a high degree of concentration and constant attention. In the relaxing DSB intervention, the subjects relaxed during the breathing training. The skin conductance levels, indicating sympathetic tone, were measured during the breathing maneuvers. Thermal detection and pain thresholds for cold and hot stimuli and profile of mood states were examined before and after the breathing sessions. The mean detection and pain thresholds showed a significant increase resulting from the relaxing DSB, whereas no significant changes of these thresholds were found associated with the attentive DSB. The mean skin conductance levels indicating sympathetic activity decreased significantly during the relaxing DSB intervention but not during the attentive DSB. Both breathing interventions showed similar reductions in negative feelings (tension, anger, and depression). Our results suggest that the way of breathing decisively influences autonomic and pain processing, thereby identifying DSB in concert with relaxation as the essential feature in the modulation of sympathetic arousal and pain perception. Wiley Periodicals, Inc.

  14. Acute pain induces an instant increase in natural killer cell cytotoxicity in humans and this response is abolished by local anaesthesia

    DEFF Research Database (Denmark)

    Greisen, J.; Hokland, Marianne; Grøfte, Thorbjørn

    1999-01-01

    We have investigated the effect of pain without tissue injury on natural killer (NK) cell activity in peripheral blood in humans and the effect of local anaesthesia on the response. Ten subjects were investigated during two sessions. First, self-controlled painful electric stimulation was applied...

  15. Increased energy expenditure and glucose oxidation during acute nontraumatic skin pain in humans.

    Science.gov (United States)

    Holland-Fischer, Peter; Greisen, Jacob; Grøfte, Thorbjørn; Jensen, Troels S; Hansen, Peter O; Vilstrup, Hendrik

    2009-04-01

    Tissue injury is accompanied by pain and results in increased energy expenditure, which may promote catabolism. The extent to which pain contributes to this sequence of events is not known. In a cross-over design, 10 healthy volunteers were examined on three occasions; first, during self-controlled nontraumatic electrical painful stimulus to the abdominal skin, maintaining an intensity of 8 on the visual analogue scale (0-10). Next, the electrical stimulus was reproduced during local analgesia and, finally, there was a control session without stimulus. Indirect calorimetry and blood and urine sampling was done in order to calculate energy expenditure and substrate utilization. During pain stimulus, energy expenditure increased acutely and reversibly by 62% (95% confidence interval, 43-83), which was abolished by local analgesia. Energy expenditure paralleled both heart rate and blood catecholamine levels. The energy expenditure increase was fuelled by all energy sources, with the largest increase in glucose utilization. The pain-related increase in energy expenditure was possibly mediated by adrenergic activity and was probably to a large extent due to increased muscle tone. These effects may be enhanced by cortical events related to the pain. The increase in glucose consumption favours catabolism. Our findings emphasize the clinical importance of pain management.

  16. Experimental Reservoirs of Human Pathogens: The Vibrio Cholerae Paradigm (7th Annual SFAF Meeting, 2012)

    Energy Technology Data Exchange (ETDEWEB)

    Colwell, Rita

    2012-06-01

    Rita Colwell on "Experimental Reservoirs of Human Pathogens: The Vibrio cholerae paradigm" at the 2012 Sequencing, Finishing, Analysis in the Future Meeting held June 5-7, 2012 in Santa Fe, New Mexico.

  17. Functional aspects of developmental toxicity of polyhalogenated aromatic hydrocarbons in experimental animals and human infants

    NARCIS (Netherlands)

    Brouwer, A.; Ahlborg, U. G.; van den Berg, M.; Birnbaum, L. S.; Boersma, E. R.; Bosveld, B.; Denison, M. S.; Gray, L. E.; Hagmar, L.; Holene, E.

    1995-01-01

    A scientific evaluation was made of functional aspects of developmental toxicity of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in experimental animals and in human infants. Persistent neurobehavioral, reproductive and

  18. The Effectiveness of Self Management Program on Pain, Fatigue, Depression, Anxiety, and Stress in Sickle Cell Patients: A Quasi-Experimental Study

    Directory of Open Access Journals (Sweden)

    Ahmadi

    2015-10-01

    Full Text Available Background Patients with sickle cell disease, who must manage serious and unpredictable complications related to their disease, particularly chronic pain, suffer from numerous psychosocial problems such as depression, anxiety, stress, and disruption of interpersonal relationships; these problems often lead to fatigue and poor quality of life. Objectives This study aimed to determine the effectiveness of self-management programs targeting pain, fatigue, depression, anxiety, and stress in sickle cell patients. Patients and Methods This was a quasi-experimental study; participants were 53 patients with sickle cell disease who were referred to the Thalassemia Clinic of Ahvaz Shafa Hospital. Participants were recruited by census in 2013. Participants received a self-management program that was implemented in five sessions over 12 weeks. Levels of fatigue, depression, anxiety, and stress were assessed before and 24 weeks after the intervention; pain was assessed during the intervention and at a 24 week post-intervention follow-up using the fatigue severity scale (FSS, DASS21, and a pain record. Descriptive statistics, Fisher’s exact test, Chi-square, independent t-tests, paired t-tests, repeated measures tests and correlations were used to analyze the data. Results Scores for fatigue, anxiety, depression, and stress after the intervention were significantly decreased compared to before the intervention (P < 0.001. Repeated measures testing showed that mean scores for frequency and duration of pain decreased significantly during the 12 weeks of intervention, as well as during the 24 weeks of follow-up (P < 0.001. Conclusions The results suggest the effectiveness of self-management programs on the reduction of pain, fatigue, anxiety, depression, and stress in sickle cell patients. Therefore, self-management programs are advisable in order to empower patients and assist their management of health-related problems.

  19. Nasal application of HSV encoding human preproenkephalin blocks craniofacial pain in a rat model of traumatic brain injury

    DEFF Research Database (Denmark)

    Sørensen, Jens Christian Hedemann; Meidahl, Anders Christian Nørgaard; Tzabazis

    2017-01-01

    pain using nasal application of a herpes simplex virus (HSV)-based vector expressing human proenkephalin (SHPE) to target the trigeminal ganglia. Mild TBI was induced in rats by the use of a modified fluid percussion model. Two days after mild TBI, following the development of facial mechanical...... lasting at least 45 days. On the other hand, nasal SHPE application 2 days post-TBI attenuated facial allodynia, reaching significance by day 4–7 and maintaining this effect throughout the duration of the experiment. Immunohistochemical examination revealed strong expression of human proenkephalin...

  20. Experimental evaluation of human-system interaction on alarm design

    International Nuclear Information System (INIS)

    Huang, F.-H.; Lee, Y.-L.; Hwang, S.-L.; Yenn, T.-C.; Yu, Y.-C.; Hsu, C.-C.; Huang, H.-W.

    2007-01-01

    This study evaluates the practicability of automatic reset alarm system in Fourth Nuclear Power Plant (FNPP) of Taiwan. The features of auto-reset alarm system include dynamic prioritization of all alarm signals and fast system reset. Two experiments were conducted to evaluate the effect of automatic/manual reset on operation time, situational awareness (SA), task load index (TLX), and subjective ratings. All participants, including Experts and Novices, took part in the experiment on the alarm system simulator with Load Rejection procedure. The experimental results imply that the auto-reset alarm system may be applied in an advanced control room under Load Rejection procedure, because all participants' operation time were reduced as well as Novice's SA were raised up. Nevertheless, to ensure operating safety in FNPP, the effects of the auto-reset alarm system in other procedures/special situations still need to be tested in the near future

  1. Method for palliation of pain in human bone cancer using therapeutic tin-117m compositions

    International Nuclear Information System (INIS)

    Srivastava, S.C.; Meinken, G.E.; Mausner, L.F.; Atkins, H.L.

    1998-01-01

    The invention provides a method for the palliation of bone pain due to cancer by the administration of a unique dosage of a tin-117m (Sn-117m) stannic chelate complex in a pharmaceutically acceptable composition. In addition, the invention provides a method for simultaneous palliation of bone pain and radiotherapy in cancer patients using compositions containing Sn-117m chelates. The invention also provides a method for palliating bone pain in cancer patients using Sn-117m-containing compositions and monitoring patient status by imaging the distribution of the Sn-117m in the patients. Also provided are pharmaceutically acceptable compositions containing Sn-117m chelate complexes for the palliation of bone pain in cancer patients. 5 figs

  2. Postural stability is altered by the stimulation of pain but not warm receptors in humans

    OpenAIRE

    Corbeil Philippe; Blouin Jean-Sébastien; Teasdale Normand

    2003-01-01

    Abstract Background It is now recognized that large diameter myelinated afferents provide the primary source of lower limb proprioceptive information for maintaining an upright standing position. Small diameter afferents transmitting noxious stimuli, however, can also influence motor behaviors. Despite the possible influence of pain on motor behaviors, the effects of pain on the postural control system have not been well documented. Methods Two cutaneous heat stimulations (experiment 1: non-n...

  3. Human brain activity associated with painful mechanical stimulation to muscle and bone

    OpenAIRE

    Maeda, Lynn; Ono, Mayu; Koyama, Tetsuo; Oshiro, Yoshitetsu; Sumitani, Masahiko; Mashimo, Takashi; Shibata, Masahiko

    2011-01-01

    Purpose The purpose of this study was to elucidate the central processing of painful mechanical stimulation to muscle and bone by measuring blood oxygen level-dependent signal changes using functional magnetic resonance imaging (fMRI). Methods Twelve healthy volunteers were enrolled. Mechanical pressure on muscle and bone were applied at the right lower leg by an algometer. Intensities were adjusted to cause weak and strong pain sensation at either target site in preliminary testing. Brain ac...

  4. Minocycline Prevents Muscular Pain Hypersensitivity and Cutaneous Allodynia Produced by Repeated Intramuscular Injections of Hypertonic Saline in Healthy Human Participants.

    Science.gov (United States)

    Samour, Mohamad Samir; Nagi, Saad Saulat; Shortland, Peter John; Mahns, David Anthony

    2017-08-01

    Minocycline, a glial suppressor, prevents behavioral hypersensitivities in animal models of peripheral nerve injury. However, clinical trials of minocycline in human studies have produced mixed results. This study addressed 2 questions: can repeated injections of hypertonic saline (HS) in humans induce persistent hypersensitivity? Can pretreatment with minocycline, a tetracycline antibiotic with microglial inhibitory effects, prevent the onset of hypersensitivity? Twenty-seven healthy participants took part in this double-blind, placebo-controlled study, consisting of 6 test sessions across 2 weeks. At the beginning of every session, pressure-pain thresholds of the anterior muscle compartment of both legs were measured to determine the region distribution and intensity of muscle soreness. To measure changes in thermal sensitivity in the skin overlying the anterior muscle compartment of both legs, quantitative sensory testing was used to measure the cutaneous thermal thresholds (cold sensation, cold pain, warm sensation, and heat pain) and a mild cooling stimulus was applied to assess the presence of cold allodynia. To induce ongoing hypersensitivity, repeated injections of HS were administered into the right tibialis anterior muscle at 48-hour intervals. In the final 2 sessions (days 9 and 14), only sensory assessments were done to plot the recovery after cessation of HS administrations and drug washout. By day 9, nontreated participants experienced a significant bilateral increase in muscle soreness (P minocycline-treated participants experienced a bilateral 70% alleviation in muscle soreness (P minocycline-treated participants showed cold allodynia. This study showed that repeated injections of HS can induce a hypersensitivity that outlasts the acute response, and the development of this hypersensitivity can be reliably attenuated with minocycline pretreatment. Four repeated injections of HS at 48-hour intervals induce a state of persistent hypersensitivity in

  5. An improved behavioural assay demonstrates that ultrasound vocalizations constitute a reliable indicator of chronic cancer pain and neuropathic pain

    Directory of Open Access Journals (Sweden)

    Selvaraj Deepitha

    2010-03-01

    Full Text Available Abstract Background On-going pain is one of the most debilitating symptoms associated with a variety of chronic pain disorders. An understanding of mechanisms underlying on-going pain, i.e. stimulus-independent pain has been hampered so far by a lack of behavioural parameters which enable studying it in experimental animals. Ultrasound vocalizations (USVs have been proposed to correlate with pain evoked by an acute activation of nociceptors. However, literature on the utility of USVs as an indicator of chronic pain is very controversial. A majority of these inconsistencies arise from parameters confounding behavioural experiments, which include novelty, fear and stress due to restrain, amongst others. Results We have developed an improved assay which overcomes these confounding factors and enables studying USVs in freely moving mice repetitively over several weeks. Using this improved assay, we report here that USVs increase significantly in mice with bone metastases-induced cancer pain or neuropathic pain for several weeks, in comparison to sham-treated mice. Importantly, analgesic drugs which are known to alleviate tumour pain or neuropathic pain in human patients significantly reduce USVs as well as mechanical allodynia in corresponding mouse models. Conclusions We show that studying USVs and mechanical allodynia in the same cohort of mice enables comparing the temporal progression of on-going pain (i.e. stimulus-independent pain and stimulus-evoked pain in these clinically highly-relevant forms of chronic pain.

  6. Adipose Derived Stromal Cell (ADSC) Injections for Pain Management of Osteoarthritis in the Human Knee Joint.

    Science.gov (United States)

    Fodor, Peter B; Paulseth, Stephen G

    2016-02-01

    This safety and feasibility study used autologous adipose-derived stromal vascular cells (the stromal vascular fraction [SVF] of adipose tissue), to treat 8 osteoarthritic knees in 6 patients of grade I to III (K-L scale) with initial pain of 4 or greater on a 10-point Visual Analog Scale (VAS). The primary objective of the study was evaluation of the safety of intra-articular injection of SVF. The secondary objective was to assess initial feasibility for reduction of pain in osteoarthritic knees. Adipose-derived SVF cells were obtained through enzymatic disaggregation of lipoaspirate, resuspension in 3 mL of Lactated Ringer's Solution, and injection directly into the intra-articular space of the knee, with a mean of 14.1 million viable, nucleated SVF cells per knee. Metrics included monitoring of adverse events and preoperative to postoperative changes in the Western Ontario and McMaster Universities Arthritis Index (WOMAC), the VAS pain scale, range of motion (ROM), timed up-and-go (TUG), and MRI. No infections, acute pain flares, or other adverse events were reported. At 3-months postoperative, there was a statistically significant improvement in WOMAC and VAS scores (P knee pain. Autologous SVF was shown to be safe and to present a new potential therapy for reduction of pain for osteoarthritis of the knee. LEVEL OF EVIDENCE 4: Therapeutic. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  7. Use of reward-penalty structures in human experimentation

    Science.gov (United States)

    Stein, A. C.; Allen, R. W.; Schwartz, S. H.

    1978-01-01

    The use of motivational techniques in human performance research is reviewed and an example study employing a reward-penalty structure to simulate the motivations inherent in a real-world situation is presented. Driver behavior in a decision-making driving scenario was studied. The task involved control of an instrumented car on a cooperative test course. Subjects were penalized monetarily for tickets and accidents and rewarded for saving driving time. Two groups were assigned different ticket penalties. The group with the highest penalties tended to drive more conservatively. However, the average total payoff to each group was the same, as the conservative drivers traded off slower driving times with lower ticket penalties.

  8. An experimental study of the emergence of human communication systems.

    Science.gov (United States)

    Galantucci, Bruno

    2005-09-10

    The emergence of human communication systems is typically investigated via 2 approaches with complementary strengths and weaknesses: naturalistic studies and computer simulations. This study was conducted with a method that combines these approaches. Pairs of participants played video games requiring communication. Members of a pair were physically separated but exchanged graphic signals through a medium that prevented the use of standard symbols (e.g., letters). Communication systems emerged and developed rapidly during the games, integrating the use of explicit signs with information implicitly available to players and silent behavior-coordinating procedures. The systems that emerged suggest 3 conclusions: (a) signs originate from different mappings; (b) sign systems develop parsimoniously; (c) sign forms are perceptually distinct, easy to produce, and tolerant to variations. 2005 Lawrence Erlbaum Associates, Inc.

  9. Effects of a home-exercise therapy programme on cervical and lumbar range of motion among nurses with neck and lower back pain: a quasi-experimental study.

    Science.gov (United States)

    Freimann, Tiina; Merisalu, Eda; Pääsuke, Mati

    2015-01-01

    Cervical and lumbar range of motion limitations are usually associated with musculoskeletal pain in the neck and lower back, and are a major health problem among nurses. Physical exercise has been evaluated as an effective intervention method for improving cervical and lumbar range of motion, and for preventing and reducing musculoskeletal pain. The purpose of this study was to investigate the effects of a home-exercise therapy programme on cervical and lumbar range of motion among intensive care unit nurses who had experienced mild to moderate musculoskeletal pain in the neck and or lower back during the previous six months. A quasi-experimental study was conducted among intensive care unit nurses at Tartu University Hospital (Estonia) between May and July 2011. Thirteen nurses who had suffered musculoskeletal pain episodes in the neck and or lower back during the previous six months underwent an 8-week home-exercise therapy programme. Eleven nurses without musculoskeletal pain formed a control group. Questions from the Nordic Musculoskeletal Questionnaire and the 11-point Visual Analogue Scale were used to select potential participants for the experimental group via an assessment of the prevalence and intensity of musculoskeletal pain. Cervical range of motion and lumbar range of motion in flexion, extension, lateral flexion and (cervical range of motion only) rotation were measured with a digital goniometer. A paired t-test was used to compare the measured parameters before and after the home-exercise therapy programme. A Student's t-test was used to analyse any differences between the experimental and control groups. After the home-exercise therapy, there was a significant increase (p cervical range of motion in flexion, extension, lateral flexion and rotation, and in lumbar range of motion in lateral flexion. Cervical range of motion in flexion was significantly higher (p cervical and lumbar range of motion among intensive care nurses. Further studies are

  10. Experimental model of human corpus cavernosum smooth muscle relaxation

    Directory of Open Access Journals (Sweden)

    Rommel P. Regadas

    2010-08-01

    Full Text Available PURPOSE: To describe a technique for en bloc harvesting of the corpus cavernosum, cavernous artery and urethra from transplant organ donors and contraction-relaxation experiments with corpus cavernosum smooth muscle. MATERIALS AND METHODS: The corpus cavernosum was dissected to the point of attachment with the crus penis. A 3 cm segment (corpus cavernosum and urethra was isolated and placed in ice-cold sterile transportation buffer. Under magnification, the cavernous artery was dissected. Thus, 2 cm fragments of cavernous artery and corpus cavernosum were obtained. Strips measuring 3 x 3 x 8 mm3 were then mounted vertically in an isolated organ bath device. Contractions were measured isometrically with a Narco-Biosystems force displacement transducer (model F-60, Narco-Biosystems, Houston, TX, USA and recorded on a 4-channel Narco-Biosystems desk model polygraph. RESULTS: Phenylephrine (1µM was used to induce tonic contractions in the corpus cavernosum (3 - 5 g tension and cavernous artery (0.5 - 1g tension until reaching a plateau. After precontraction, smooth muscle relaxants were used to produce relaxation-response curves (10-12M to 10-4 M. Sodium nitroprusside was used as a relaxation control. CONCLUSION: The harvesting technique and the smooth muscle contraction-relaxation model described in this study were shown to be useful instruments in the search for new drugs for the treatment of human erectile dysfunction.

  11. Relevance of experimental animal studies to the human experience

    International Nuclear Information System (INIS)

    Fry, R.J.M.

    1982-01-01

    Animal experiments are being used to examine a number of physical and biological factors that influence risk estimations though not usually in coordination with epidemiologists. It is clear that the different mechanisms involved in different types of tumors are reflected in the diversity of dose-response relationships. The forms of the dose-response relationships are influenced by both the initial events and their expression. Evidence is accumulating that many initiated cells do not get expressed as overt cancers and host factors may play a major role in the expression of potential tumor cells. There is a need for information about the relationship of the natural incidence and susceptibility to radiation induction for more tumor types. Such experiments will help answer the question of which risk estimate models are appropriate for different tumor types and can be carried out on animals. Perhaps because of the importance of host factors risk estimates as a percentage of the natural incidence appear to be similar for human beings and mice for a small number of tumor types. The elucidation of the mechanisms involved in different tissues while a slow business remains an important role of animal experiments

  12. Drugs to foster kidney regeneration in experimental animals and humans.

    Science.gov (United States)

    Gagliardini, Elena; Benigni, Ariela

    2014-01-01

    The incidence of kidney diseases is increasing worldwide and they are emerging as a major public health problem. Once mostly considered inexorable, renal disease progression can now be halted and lesions can even regress with drugs such as angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II type I receptor blockers, indicating the possibility of kidney repair. The discovery of renal progenitor cells lining the Bowman capsule of adult rat and human kidneys has shed light on the mechanism of repair by ACEi. Parietal progenitors are a reservoir of cells that contribute to podocyte turnover in physiological conditions. In the early phases of renal disease these progenitors migrate chaotically and subsequently proliferate, accumulating in Bowman's space. The abnormal behavior of parietal progenitors is sustained by the activation of CXCR4 receptors in response to an increased production of the chemokine SDF-1 by podocytes activated by the inflammatory environment. Ang II, via the AT1 receptor, also contributes to progenitor cell proliferation. The CXCR4/SDF-1 and Ang II/AT1 receptor pathogenic pathways both pave the way for lesion formation and subsequent sclerosis. ACEi normalize the CXCR4 and AT1 receptor expression on progenitors, limiting their proliferation, concomitant with the regression of hyperplastic lesions in animals, and in a patient with crescentic glomerulopathy. Understanding the molecular and cellular determinants of regeneration triggered by renoprotective drugs will reveal novel pathways that might be challenged or targeted by pharmacological therapy. © 2014 S. Karger AG, Basel.

  13. Colorectal carcinogenesis: Review of human and experimental animal studies

    Directory of Open Access Journals (Sweden)

    Tanaka Takuji

    2009-01-01

    Full Text Available This review gives a comprehensive overview of cancer development and links it to the current understanding of tumorigenesis and malignant progression in colorectal cancer. The focus is on human and murine colorectal carcinogenesis and the histogenesis of this malignant disorder. A summary of a model of colitis-associated colon tumorigenesis (an AOM/DSS model will also be presented. The earliest phases of colorectal oncogenesis occur in the normal mucosa, with a disorder of cell replication. The large majority of colorectal malignancies develop from an adenomatous polyp (adenoma. These can be defined as well-demarcated masses of epithelial dysplasia, with uncontrolled crypt cell proliferation. When neoplastic cells pass through the muscularis mucosa and infiltrate the submucosa, they are malignant. Carcinomas usually originate from pre-existing adenomas, but this does not imply that all polyps undergo malignant changes and does not exclude de novo oncogenesis. Besides adenomas, there are other types of pre-neoplasia, which include hyperplastic polyps, serrated adenomas, flat adenomas and dysplasia that occurs in the inflamed colon in associated with inflammatory bowel disease. Colorectal neoplasms cover a wide range of pre-malignant and malignant lesions, many of which can easily be removed during endoscopy if they are small. Colorectal neoplasms and/or pre-neoplasms can be prevented by interfering with the various steps of oncogenesis, which begins with uncontrolled epithelial cell replication, continues with the formation of adenomas and eventually evolves into malignancy. The knowledge described herein will help to reduce and prevent this malignancy, which is one of the most frequent neoplasms in some Western and developed countries.

  14. TRPM8 axonal expression is decreased in painful human teeth with irreversible pulpitis and cold hyperalgesia

    Science.gov (United States)

    Alvarado, Lisa T.; Perry, Griffin M.; Hargreaves, Kenneth. M.; Henry, Michael A.

    2009-01-01

    Pulpitis pain may be triggered by a cold stimulus, yet the cellular mechanisms responsible for this phenomenon are largely unknown. One possible mechanism involves the direct activation of cold-responsive thermoreceptors. The purpose of this study was to evaluate the possible role of the TRPM8 thermoreceptor in cold-mediated noxious pulpal pain mechanisms by comparing expression patterns in pulpal nerves from healthy control molars to cold-sensitive painful molars with irreversible pulpitis. Samples were identically processed with the indirect immunofluorescence method and images obtained with confocal microscopy. The immunofluorescence intensity and area occupied by TRPM8 within N52/PGP9.5 identified nerve fibers were quantified. Results showed that relative to normal samples, TRPM8 nerve area expression was significantly less in the cold-sensitive painful samples (34.9% vs. 8%, p<0.03), but with no significant difference in immunofluorescence intensity between the two groups. These results suggest that TRPM8 is most likely not involved in cold-mediated noxious pulpal pain mechanisms. PMID:17889683

  15. Human brain activity associated with painful mechanical stimulation to muscle and bone.

    Science.gov (United States)

    Maeda, Lynn; Ono, Mayu; Koyama, Tetsuo; Oshiro, Yoshitetsu; Sumitani, Masahiko; Mashimo, Takashi; Shibata, Masahiko

    2011-08-01

    The purpose of this study was to elucidate the central processing of painful mechanical stimulation to muscle and bone by measuring blood oxygen level-dependent signal changes using functional magnetic resonance imaging (fMRI). Twelve healthy volunteers were enrolled. Mechanical pressure on muscle and bone were applied at the right lower leg by an algometer. Intensities were adjusted to cause weak and strong pain sensation at either target site in preliminary testing. Brain activation in response to mechanical nociceptive stimulation targeting muscle and bone were measured by fMRI and analyzed. Painful mechanical stimulation targeting muscle and bone activated the common areas including bilateral insula, anterior cingulate cortex, posterior cingulate cortex, secondary somatosensory cortex (S2), inferior parietal lobe, and basal ganglia. The contralateral S2 was more activated by strong stimulation than by weak stimulation. Some areas in the basal ganglia (bilateral putamen and caudate nucleus) were more activated by muscle stimulation than by bone stimulation. The putamen and caudate nucleus may have a more significant role in brain processing of muscle pain compared with bone pain.

  16. Effects of experimental muscle pain on force variability during task-related and three directional isometric force task

    DEFF Research Database (Denmark)

    Mista, Christian Ariel; Graven-Nielsen, Thomas

    2013-01-01

    was measured using sample entropy (SEn). Three-way repeated measures ANOVA with factors level of contraction, pain/control, and time were performed for the CV, the CoP, and the SEn of each component of the force. In the tangential forces, no significant effects were found for the 3D matching tasks. The ANOVA.......05). In the task-related force, no significant effects were found for the CV during the three-dimensional task or for the task-related task. Finally, the ANOVA analysis of sample entropy showed a significant interaction between pain/control and time (P

  17. Development of an Experimental Measurement System for Human Error Characteristics and a Pilot Test

    International Nuclear Information System (INIS)

    Jang, Tong-Il; Lee, Hyun-Chul; Moon, Kwangsu

    2017-01-01

    Some items out of individual and team characteristics were partially selected, and a pilot test was performed to measure and evaluate them using the experimental measurement system of human error characteristics. It is one of the processes to produce input data to the Eco-DBMS. And also, through the pilot test, it was tried to take methods to measure and acquire the physiological data, and to develop data format and quantification methods for the database. In this study, a pilot test to measure the stress and the tension level, and team cognitive characteristics out of human error characteristics was performed using the human error characteristics measurement and experimental evaluation system. In an experiment measuring the stress level, physiological characteristics using EEG was measured in a simulated unexpected situation. As shown in results, although this experiment was pilot, it was validated that relevant results for evaluating human error coping effects of workers’ FFD management guidelines and unexpected situation against guidelines can be obtained. In following researches, additional experiments including other human error characteristics will be conducted. Furthermore, the human error characteristics measurement and experimental evaluation system will be utilized to validate various human error coping solutions such as human factors criteria, design, and guidelines as well as supplement the human error characteristics database.

  18. Experimental design and reporting standards for improving the internal validity of pre-clinical studies in the field of pain: Consensus of the IMI-Europain consortium

    DEFF Research Database (Denmark)

    Knopp, K.L.; Stenfors, C.; Baastrup, Cathrine Søndergaard

    2015-01-01

    that recommendations on how to improve these factors are warranted. Methods Members of Europain, a pain research consortium funded by the European Innovative Medicines Initiative (IMI), developed internal recommendations on how to improve the reliability of pre-clinical studies between laboratories. This guidance...... and conduct, and data analysis and interpretation. Key principles such as sample size calculation, a priori definition of a primary efficacy measure, randomization, allocation concealments, and blinding are discussed. In addition, considerations of how stress and normal rodent physiology impact outcome...... development in order to estimate possible publication bias is discussed. Conclusions More systematic research is needed to analyze how inadequate internal validity and/or experimental bias may impact reproducibility across pre-clinical pain studies. Addressing the potential threats to internal validity...

  19. Temporal summation of heat pain in humans: Evidence supporting thalamocortical modulation.

    Science.gov (United States)

    Tran, Tuan D; Wang, Heng; Tandon, Animesh; Hernandez-Garcia, Luis; Casey, Kenneth L

    2010-07-01

    Noxious cutaneous contact heat stimuli (48 degrees C) are perceived as increasingly painful when the stimulus duration is extended from 5 to 10s, reflecting the temporal summation of central neuronal activity mediating heat pain. However, the sensation of increasing heat pain disappears, reaching a plateau as stimulus duration increases from 10 to 20s. We used functional magnetic resonance imaging (fMRI) in 10 healthy subjects to determine if active central mechanisms could contribute to this psychophysical plateau. During heat pain durations ranging from 5 to 20s, activation intensities in the bilateral orbitofrontal cortices and the activation volume in the left primary (S1) somatosensory cortex correlated only with perceived stimulus intensity and not with stimulus duration. Activation volumes increased with both stimulus duration and perceived intensity in the left lateral thalamus, posterior insula, inferior parietal cortex, and hippocampus. In contrast, during the psychophysical plateau, both the intensity and volume of thalamic and cortical activations in the right medial thalamus, right posterior insula, and left secondary (S2) somatosensory cortex continued to increase with stimulus duration but not with perceived stimulus intensity. Activation volumes in the left medial and right lateral thalamus, and the bilateral mid-anterior cingulate, left orbitofrontal, and right S2 cortices also increased only with stimulus duration. The increased activity of specific thalamic and cortical structures as stimulus duration, but not perceived intensity, increases is consistent with the recruitment of a thalamocortical mechanism that participates in the modulation of pain-related cortical responses and the temporal summation of heat pain. Published by Elsevier B.V.

  20. Postural stability is altered by the stimulation of pain but not warm receptors in humans

    Directory of Open Access Journals (Sweden)

    Corbeil Philippe

    2003-10-01

    Full Text Available Abstract Background It is now recognized that large diameter myelinated afferents provide the primary source of lower limb proprioceptive information for maintaining an upright standing position. Small diameter afferents transmitting noxious stimuli, however, can also influence motor behaviors. Despite the possible influence of pain on motor behaviors, the effects of pain on the postural control system have not been well documented. Methods Two cutaneous heat stimulations (experiment 1: non-noxious 40 degrees C; experiment 2: noxious 45 degrees C were applied bilaterally on the calves of the subject with two thermal grills to stimulate A delta and C warm receptors and nociceptors in order to examine their effects on postural stability. The non-noxious stimulation induced a gentle sensation of warmth and the noxious stimulation induced a perception of heat pain (visual analogue scores of 0 and 46 mm, respectively. For both experiments, ten healthy young adults were tested with and without heat stimulations of the lower limbs while standing upright on a force platform with eyes open, eyes closed and eyes closed with tendon co-vibration of tibialis anterior and triceps surae muscles. The center of pressure displacements were analyzed to examine how both stimulations affected the regulation of quiet standing and if the effects were exacerbated when vision was removed or ankle proprioception perturbed. Results The stimulation of the warm receptors (40 degrees C did not induce any postural deterioration. With pain (45 degrees C, subjects showed a significant increase in standard deviation, range and mean velocity of postural oscillations as well as standard deviation of the center of pressure velocity. The effects of heat pain were exacerbated when subjects had both their eyes closed and ankle tendons vibrated (increased standard deviation of the center of pressure velocity and mean velocity of the center of pressure. Conclusions A non

  1. Postural stability is altered by the stimulation of pain but not warm receptors in humans.

    Science.gov (United States)

    Blouin, Jean-Sébastien; Corbeil, Philippe; Teasdale, Normand

    2003-10-17

    It is now recognized that large diameter myelinated afferents provide the primary source of lower limb proprioceptive information for maintaining an upright standing position. Small diameter afferents transmitting noxious stimuli, however, can also influence motor behaviors. Despite the possible influence of pain on motor behaviors, the effects of pain on the postural control system have not been well documented. Two cutaneous heat stimulations (experiment 1: non-noxious 40 degrees C; experiment 2: noxious 45 degrees C) were applied bilaterally on the calves of the subject with two thermal grills to stimulate A delta and C warm receptors and nociceptors in order to examine their effects on postural stability. The non-noxious stimulation induced a gentle sensation of warmth and the noxious stimulation induced a perception of heat pain (visual analogue scores of 0 and 46 mm, respectively). For both experiments, ten healthy young adults were tested with and without heat stimulations of the lower limbs while standing upright on a force platform with eyes open, eyes closed and eyes closed with tendon co-vibration of tibialis anterior and triceps surae muscles. The center of pressure displacements were analyzed to examine how both stimulations affected the regulation of quiet standing and if the effects were exacerbated when vision was removed or ankle proprioception perturbed. The stimulation of the warm receptors (40 degrees C) did not induce any postural deterioration. With pain (45 degrees C), subjects showed a significant increase in standard deviation, range and mean velocity of postural oscillations as well as standard deviation of the center of pressure velocity. The effects of heat pain were exacerbated when subjects had both their eyes closed and ankle tendons vibrated (increased standard deviation of the center of pressure velocity and mean velocity of the center of pressure). A non-noxious stimulation (40 degrees C) of the small diameter afferents is not a

  2. Randomized clinical trial: efficacy and safety of PPC-5650 on experimental esophageal pain and hyperalgesia in healthy volunteers

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Nielsen, Lecia Møller; Larsen, Isabelle Myriam

    2015-01-01

    OBJECTIVE: Gastroesophageal reflux disease (GERD) is a common condition associated with symptoms as heart burn, regurgitation, chest pain, and gastrointestinal discomfort. PPC-5650 is a new pharmacological agent that can modulate acid-sensing ion channel activity, potentially leading to reduction...

  3. The Effect of Intrathecal Administration of Muscimol on Modulation of Neuropathic Pain Symptoms Resulting from Spinal Cord Injury; an Experimental Study

    Directory of Open Access Journals (Sweden)

    Marjan Hosseini

    2014-09-01

    Full Text Available Introduction: Neuropathic pain can be very difficult to treat and it is one of the important medical challenging about pain treatments. Muscimol as a new agonist of gamma-Aminobutyric acid receptor type A (GABAA have been introduced for pain management. Thus, the present study was performed to evaluate the pain alleviating effect of intrathecal injection of different doses of muscimol as GABAA receptor agonist in spinal cord injury (SCI model of neuropathic pain. Methods: In the present experimental study male Wistar rats were treated by muscimol 0.01, 0.1 or 1 µg/10ul, intrathecally (i.t. three weeks after induction of spinal cord injury using compression injury model. Neuropathic pain symptoms were assessed at before treatment, 15 minutes, one hour and three hours after muscimol administration. The time of peak effect and optimum dosage was assessed by repeated measures analysis of variance and analysis of covariance, respectively. Results: Muscimol with the dose of 0.01 µg in 15 minutes caused to improve the thermal hyperalgesia (df: 24, 5; F= 6.6; p<0.001, mechanical hyperalgesia (df: 24, 5; F= 7.8; p<0.001, cold allodynia (df: 24, 5; F= 6.96; p<0.001, and mechanical allodynia (df: 24, 5; F= 15.7; p<0.001. The effect of doses of 0.1 µg and 1 µg were also significant. In addition, the efficacy of different doses of muscimol didn't have difference on thermal hyperalgesia (df: 24, 5; F= 1.52; p= 0.24, mechanical hyperalgesia (df: 24, 5; F= 0.3; p= -0.75, cold allodynia (df: 24, 5; F= 0.8; p= -0.56, and mechanical allodynia (df: 24, 5; F= 1.75; p= 0.86. Conclusion: The finding of the present study revealed that using muscimol with doses of 0.01µg, 0.1µg, and 1 µg reduces the symptoms of neuropathic pain. Also the effect of GABAA agonist is short term and its effectiveness gradually decreases by time.

  4. Towards Development of a Dermal Pain Model: In Vitro Activation of Rat and Human Transient Receptor Potential Ankyrin Repeat 1 and Safe Dermal Injection of o-Chlorobenzylidene Malononitrile to Rat.

    Science.gov (United States)

    Annas, Anita; Berg, Anna-Lena; Nyman, Eva; Meijer, Thomas; Lundgren, Viveka; Franzén, Bo; Ståhle, Lars

    2015-12-01

    During clinical development of analgesics, it is important to have access to pharmacologically specific human pain models. o-Chlorobenzylidene malononitrile (CS) is a selective and potent agonist of the transient receptor potential ankyrin repeat 1 (TRPA1), which is a transducer molecule in nociceptors sensing reactive chemical species. While CS has been subject to extensive toxicological investigations in animals and human beings, its effects on intradermal or subcutaneous injection have not previously been reported. We have investigated the potential of CS to be used as an agonist on TRPA1 in human experimental pain studies. A calcium influx assay was used to confirm the capacity of CS to activate TRPA1 with >100,000 times the selectivity over the transient receptor potential vanilloid receptor 1. CS dose-dependently (EC50 0.9 μM) released calcitonin gene-related peptide in rat dorsal root ganglion cultures, supporting involvement in pain signalling. In a local tolerance study, injection of a single intradermal dose of 20 mM CS to rats resulted in superficial, circular crusts at the injection sites after approximately 4 days. The histopathology evaluation revealed a mild, acute inflammatory reaction in the epidermis and dermis at the intradermal CS injection site 1 day after administration. After 14 days, the epidermal epithelium was fully restored. The symptoms were not considered to be adverse, and it is suggested that doses up to 20 μL of 20 mM CS can be safely administered to human beings. In conclusion, our data support development of a CS human dermal pain model. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  5. Salmon and human thrombin differentially regulate radicular pain, glial-induced inflammation and spinal neuronal excitability through protease-activated receptor-1.

    Directory of Open Access Journals (Sweden)

    Jenell R Smith

    Full Text Available Chronic neck pain is a major problem with common causes including disc herniation and spondylosis that compress the spinal nerve roots. Cervical nerve root compression in the rat produces sustained behavioral hypersensitivity, due in part to the early upregulation of pro-inflammatory cytokines, the sustained hyperexcitability of neurons in the spinal cord and degeneration in the injured nerve root. Through its activation of the protease-activated receptor-1 (PAR1, mammalian thrombin can enhance pain and inflammation; yet at lower concentrations it is also capable of transiently attenuating pain which suggests that PAR1 activation rate may affect pain maintenance. Interestingly, salmon-derived fibrin, which contains salmon thrombin, attenuates nerve root-induced pain and inflammation, but the mechanisms of action leading to its analgesia are unknown. This study evaluates the effects of salmon thrombin on nerve root-mediated pain, axonal degeneration in the root, spinal neuronal hyperexcitability and inflammation compared to its human counterpart in the context of their enzymatic capabilities towards coagulation substrates and PAR1. Salmon thrombin significantly reduces behavioral sensitivity, preserves neuronal myelination, reduces macrophage infiltration in the injured nerve root and significantly decreases spinal neuronal hyperexcitability after painful root compression in the rat; whereas human thrombin has no effect. Unlike salmon thrombin, human thrombin upregulates the transcription of IL-1β and TNF-α and the secretion of IL-6 by cortical cultures. Salmon and human thrombins cleave human fibrinogen-derived peptides and form clots with fibrinogen with similar enzymatic activities, but salmon thrombin retains a higher enzymatic activity towards coagulation substrates in the presence of antithrombin III and hirudin compared to human thrombin. Conversely, salmon thrombin activates a PAR1-derived peptide more weakly than human thrombin. These

  6. The Effect of Patellar Denervation by Circumpatellar Electrocautery on Anterior Knee Pain Following Total Knee Replacement – An Experimental Study

    Directory of Open Access Journals (Sweden)

    Balaji Zacharia

    2017-07-01

    Full Text Available ABSTRACT OBJECTIVES Anterior knee pain is a common problem in patients who have undergone TKR which causes dissatisfaction among them. There are Various methods for prevention of anterior knee pain following TKR .The  objective of this study is to determine the  effect of circumpatellar electrocautery on anterior knee pain following TKR and to compare the results with that of those patients who have undergone TKR without circumpatellar denervation. METHODS This is a cohort study conducted in Dept. of Orthopedics, Govt. Medical College, Kozhikode,kerala, 2014. Total sample size was 90.out of which 2 patients died during the study period. We lost follow up of 7 patients.  Among the remaining 81 patients 42 had undergone TKR with circumpatellar denervation using electocautery and 39 without circumpatellar denervation. They were kept under follow up. Patients were followed up postoperatively at 1 month, 3 months, 6 months and at one year. At all postoperative visits, a clinical score was determined using the Knee Society score and the clinical anterior knee pain rating system described by Waters and Bentley RESULTS There is no statistically significant difference in AKP score between both groups.There is a statistically significant difference in the knee society score at 1st month(p value <.001.  But there is no difference on further follow up visits . CONCLUSION There is no statistically significant difference between final outcome of patients who underwent patella denervation using circumpatellar electrocauterisation and those without denervation  with respect to anterior knee pain among patients who have undergone TKR.

  7. A novel model of inflammatory pain in human skin involving topical application of sodium lauryl sulfate.

    Science.gov (United States)

    Petersen, L J; Lyngholm, A M; Arendt-Nielsen, L

    2010-09-01

    Sodium lauryl sulfate (SLS) is a known irritant. It releases pro-inflammatory mediators considered pivotal in inflammatory pain. The sensory effects of SLS in the skin remain largely unexplored. In this study, SLS was evaluated for its effect on skin sensory functions. Eight healthy subjects were recruited for this study. Skin sites were randomized to topical SLS 0.25, 0.5, 1, 2% and vehicle for 24 h. Topical capsaicin 1% was applied for 30 min at 24 h after SLS application. Assessments included laser Doppler imaging of local vasodilation and flare reactions, rating of spontaneous pain, assessment of primary thermal and tactile hyperalgesia, and determination of secondary dynamic and static hyperalgesia. SLS induced significant and dose-dependent local inflammation and primary hyperalgesia to tactile and thermal stimulation at 24 h after application, with SLS 2% treatment eliciting results comparable to those observed following treatment with capsaicin 1%. SLS induced no spontaneous pain, small areas of flare, and minimal secondary hyperalgesia. The primary hyperalgesia vanished within 2-3 days, whereas the skin inflammation persisted and was only partly normalized by Day 6. SLS induces profound perturbations of skin sensory functions lasting 2-3 days. SLS-induced inflammation may be a useful model for studying the mechanisms of inflammatory pain.

  8. Pain, wheal and flare in human forearm skin induced by bradykinin and 5-hydroxytryptamine

    DEFF Research Database (Denmark)

    Jensen, Kai; Tuxen, C; Pedersen-Bjergaard, U

    1990-01-01

    Pain was induced in 19 healthy individuals by double-blind injections into the forearm skin of 0.05 ml of physiological saline with or without active substances added. Bradykinin (0.5 nmol), 5-hydroxytryptamine (0.5 nmol) and a mixture of the two substances in half dosage (0.25 nmol + 0.25 nmol...

  9. Dynamics of the human pelvis : Identification methodology for low back pain diagnosis

    NARCIS (Netherlands)

    Conza, N.E.

    2006-01-01

    This project finds its justification in the vast economic and social impact that musculoskeletal disorders have at a global level. Many cases of low back pain, which is the most relevant disorder among them, remain a mystery as far as their pathology is concerned. The assumption underlying this work

  10. Establishing experimental model of human internal carotid artery siphon segment in canine common carotid artery

    International Nuclear Information System (INIS)

    Cui Xuee; Li Minghua; Wang Yongli; Cheng Yingsheng; Li Wenbin

    2005-01-01

    Objective: To study the feasibility of establishing experimental model of human internal carotid artery siphon segment in canine common carotid artery (CCA) by end-to-end anastomoses of one side common carotid artery segment with the other side common carotid artery. Methods: Surgical techniques were used to make siphon model in 8 canines. One side CCA was taken as the parent artery and anastomosing with the cut off contra-lateral CCA segment which has passed through within the S-shaped glass tube. Two weeks after the creation of models angiography showed the model siphons were patent. Results: Experimental models of human internal carotid artery siphon segment were successfully made in all 8 dogs. Conclusions: It is practically feasible to establish experimental canine common carotid artery models of siphon segment simulating human internal carotid artery. (authors)

  11. Genetic Contributions to Clinical Pain and Analgesia: Avoiding Pitfalls in Genetic Research

    Science.gov (United States)

    Kim, Hyungsuk; Clark, David; Dionne, Raymond A.

    2010-01-01

    Understanding the genetic basis of human variations in pain is critical to elucidating the molecular basis of pain sensitivity, variable responses to analgesic drugs, and, ultimately, to individualized treatment of pain and improved public health. With the help of recently accumulated knowledge and advanced technologies, pain researchers hope to gain insight into genetic mechanisms of pain and eventually apply this knowledge to pain treatment. Perspective We critically reviewed the published literature to examine the strength of evidence supporting genetic influences on clinical and human experimental pain. Based on this evidence and the experience of false associations that have occurred in other related disciplines, we provide recommendations for avoiding pitfalls in pain genetic research. PMID:19559388

  12. The Biological Effects of Quadripolar Radiofrequency Sequential Application: A Human Experimental Study

    OpenAIRE

    Nicoletti, Giovanni; Cornaglia, Antonia Icaro; Faga, Angela; Scevola, Silvia

    2014-01-01

    Objective: An experimental study was conducted to assess the effectiveness and safety of an innovative quadripolar variable electrode configuration radiofrequency device with objective measurements in an ex vivo and in vivo human experimental model. Background data: Nonablative radiofrequency applications are well-established anti-ageing procedures for cosmetic skin tightening. Methods: The study was performed in two steps: ex vivo and in vivo assessments. In the ex vivo assessments the radio...

  13. Analgesic and antihyperalgesic effects of melatonin in a human inflammatory pain model

    DEFF Research Database (Denmark)

    Andersen, Lars P H; Gögenur, Ismail; Fenger, Andreas Q

    2015-01-01

    . The design was a randomized, double-blind, placebo-controlled, three-arm crossover study. Each volunteer participated in 3 identical study sessions with intravenous administration of placebo, melatonin 10 mg, or melatonin 100 mg. Sixty minutes after bolus injection of study medication, a BI was induced...... by a computerized contact thermode (47.0°C, 420 seconds, 5.0 × 2.5 cm). Pain ratings during the BI and quantitative sensory testing at baseline and at 1, 2, 4, and 6 hours after the BI were performed. Quantitative sensory testing included assessments of secondary hyperalgesia areas, mechanical and thermal...... thresholds in the BI area, and pressure algometry. Furthermore, markers of inflammation, skin-reflectance spectrophotometry, and high-resolution ultrasonography were applied to measure skin erythema and dermal thickness in the BI area. Pain during the BI and secondary hyperalgesia areas were defined...

  14. Similarities between exercise-induced hypoalgesia and conditioned pain modulation in humans

    DEFF Research Database (Denmark)

    Vægter, Henrik Bjarke; Handberg, Gitte; Graven-Nielsen, Thomas

    2014-01-01

    Pain inhibitory mechanisms are often assessed by paradigms of exercise-induced hypoalgesia (EIH) and conditioned pain modulation (CPM). In this study it was hypothesised that the spatial and temporal manifestations of EIH and CPM were comparable. Eighty healthy subjects (40 females), between 18......-65 years participated in this randomized repeated-measures crossover trial with data collection on two different days. CPM was assessed by two different cold pressor tests (hand,foot). EIH was assessed through two intensities of aerobic bicycling exercises and two intensities of isometric muscle...... tests and after all of the exercise conditions, except low intensity bicycling. EIH after bicycling was increased in women compared to men. CPM and the EIH response after isometric exercises were comparable in men and women and not affected by age. The EIH response was larger in the exercising body part...

  15. [Right extremities pain caused by a malacia lesion in the left putamen:a resting functional magnetic resonance imaging of the marginal division of the human brain].

    Science.gov (United States)

    Chen, Zhi-Ye; Ma, Lin

    2014-04-01

    To explore the role of marginal division of the human brain in the pain modulation. Resting functional magnetic resonance imaging was applied in a patient with right extremities pain caused by a malacia lesion in the left putamen and in 8 healthy volunteers. Marginal division was defined using manual drawing on structure images, and was applied to the computation of fuctional connectivity maps. The functional connectivities in the left marginal division showed an evident decrease in the patient when compared with healthy controls. These connectivities were mainly located in the bilateral head of caudate nucleus, putamen, and left globus pallidus. The marginal division may be involved in the pain modulation.

  16. Deep pain thresholds in the distal limbs of healthy human subjects.

    Science.gov (United States)

    Rolke, R; Andrews Campbell, K; Magerl, W; Treede, R-D

    2005-02-01

    Pressure pain thresholds (PPTs) in distal limbs have been under-investigated despite their potential clinical importance. Therefore, we compared PPTs over nail bed, bony prominences, and muscle in distal parts of upper and lower limbs. We investigated 12 healthy subjects using three handheld devices: a spring-loaded, analogue pressure threshold meter (PTM) with two operating ranges, and an electronic Algometer. PPTs were determined with three series of ascending stimulus intensities with a ramp of about 50 kPa/s. PPTs were normally distributed in logarithmic space. PPTs over different tissues varied significantly (ANOVA, pAlgometer than with PTMs (ANOVA, ptesting over muscle. There was no significant right-left difference (ANOVA, p=0.33). In spite of considerable variability across subjects, reproducibility within subjects was high (correlation coefficients>0.90). For within-subject comparisons, threshold elevations beyond 33-43% would be abnormal (95% confidence intervals), whereas only deviations from the group mean by at least a factor of two would be abnormal with respect to absolute normative values. PPTs over distal muscles were comparable to published values on proximal limb and trunk muscles. These findings suggest that pressure pain testing over distal muscles may be a sensitive test for deep pain sensitivity and that the simple and less expensive devices are sufficient for testing this tissue type. Intra-individual site-to-site comparisons will be more sensitive than absolute normative values.

  17. Extensibility and stiffness of the hamstrings in patients with nonspecific low back pain

    NARCIS (Netherlands)

    Halbertsma, JPK; Goeken, LNH; Hof, AL; Groothoff, JW; Eisma, WH; Göeken, L.N.H.

    Objective: To investigate the extensibility and stiffness of the hamstrings in patients with nonspecific low back pain (LBP). Design: An experimental design. Setting: A university laboratory for human movement analysis in a department of rehabilitation medicine. Participants: Forty subjects, a

  18. The development of human factors technologies -The development of human factors experimental evaluation techniques-

    International Nuclear Information System (INIS)

    Shim, Bong Sik; Oh, In Suk; Cha, Kyung Hoh; Lee, Hyun Chul

    1995-07-01

    In this year, we studied the followings: 1) Development of operator mental workload evaluation techniques, 2) Development of a prototype for preliminary human factors experiment, 3) Suitability test of information display on a large scale display panel, 4) Development of guidelines for VDU-based control room design, 5) Development of integrated test facility (ITF). 6) Establishment of an eye tracking system, and we got the following results: 1) Mental workload evaluation techniques for MMI evaluation, 2) PROTOPEX (PROTOtype for preliminary human factors experiment) for preliminary human factors experiments, 3) Usage methods of APTEA (Analysis-Prototyping-Training-Experiment-Analysis) experiment design, 4) Design guidelines for human factors verification, 5) Detail design requirements and development plan of ITF, 6) Eye movement measurement system. 38 figs, 20 tabs, 54 refs. (Author)

  19. Cadmium osteotoxicity in experimental animals: Mechanisms and relationship to human exposures

    International Nuclear Information System (INIS)

    Bhattacharyya, Maryka H.

    2009-01-01

    Extensive epidemiological studies have recently demonstrated increased cadmium exposure correlating significantly with decreased bone mineral density and increased fracture incidence in humans at lower exposure levels than ever before evaluated. Studies in experimental animals have addressed whether very low concentrations of dietary cadmium can negatively impact the skeleton. This overview evaluates results in experimental animals regarding mechanisms of action on bone and the application of these results to humans. Results demonstrate that long-term dietary exposures in rats, at levels corresponding to environmental exposures in humans, result in increased skeletal fragility and decreased mineral density. Cadmium-induced demineralization begins soon after exposure, within 24 h of an oral dose to mice. In bone culture systems, cadmium at low concentrations acts directly on bone cells to cause both decreases in bone formation and increases in bone resorption, independent of its effects on kidney, intestine, or circulating hormone concentrations. Results from gene expression microarray and gene knock-out mouse models provide insight into mechanisms by which cadmium may affect bone. Application of the results to humans is considered with respect to cigarette smoke exposure pathways and direct vs. indirect effects of cadmium. Clearly, understanding the mechanism(s) by which cadmium causes bone loss in experimental animals will provide insight into its diverse effects in humans. Preventing bone loss is critical to maintaining an active, independent lifestyle, particularly among elderly persons. Identifying environmental factors such as cadmium that contribute to increased fractures in humans is an important undertaking and a first step to prevention.

  20. Stochastic estimation of human shoulder impedance with robots: an experimental design.

    Science.gov (United States)

    Park, Kyungbin; Chang, Pyung Hun

    2011-01-01

    Previous studies assumed the shoulder as a hinge joint during human arm impedance measurement. This is obviously a vast simplification since the shoulder is a complex of several joints with multiple degrees of freedom. In the present work, a practical methodology for more general and realistic estimation of human shoulder impedance is proposed and validated with a spring array. It includes a gravity compensation scheme, which is developed and used for the experiments with a spatial three degrees of freedom PUMA-type robot. The experimental results were accurate and reliable, and thus it has shown a strong potential of the proposed methodology in the estimation of human shoulder impedance. © 2011 IEEE

  1. Ethics of animal research in human disease remediation, its institutional teaching; and alternatives to animal experimentation.

    Science.gov (United States)

    Cheluvappa, Rajkumar; Scowen, Paul; Eri, Rajaraman

    2017-08-01

    Animals have been used in research and teaching for a long time. However, clear ethical guidelines and pertinent legislation were instated only in the past few decades, even in developed countries with Judeo-Christian ethical roots. We compactly cover the basics of animal research ethics, ethical reviewing and compliance guidelines for animal experimentation across the developed world, "our" fundamentals of institutional animal research ethics teaching, and emerging alternatives to animal research. This treatise was meticulously constructed for scientists interested/involved in animal research. Herein, we discuss key animal ethics principles - Replacement/Reduction/Refinement. Despite similar undergirding principles across developed countries, ethical reviewing and compliance guidelines for animal experimentation vary. The chronology and evolution of mandatory institutional ethical reviewing of animal experimentation (in its pioneering nations) are summarised. This is followed by a concise rendition of the fundamentals of teaching animal research ethics in institutions. With the advent of newer methodologies in human cell-culturing, novel/emerging methods aim to minimise, if not avoid the usage of animals in experimentation. Relevant to this, we discuss key extant/emerging alternatives to animal use in research; including organs on chips, human-derived three-dimensional tissue models, human blood derivates, microdosing, and computer modelling of various hues. © 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

  2. Tribology of skin : review and analysis of experimental results for the friction coefficient of human skin

    NARCIS (Netherlands)

    Derler, S.; Gerhardt, L.C.

    2012-01-01

    In this review, we discuss the current knowledge on the tribology of human skin and present an analysis of the available experimental results for skin-friction coefficients. Starting with an overview on the factors influencing the friction behaviour of skin, we discuss the up-to-date existing

  3. Experimental evidence of human recreational disturbance effects on bird-territory establishment.

    Science.gov (United States)

    Bötsch, Yves; Tablado, Zulima; Jenni, Lukas

    2017-07-12

    The worldwide increase in human outdoor activities raises concerns for wildlife. Human disturbances, even at low levels, are likely to impact species during sensitive periods of the annual cycle. However, experimental studies during the putative sensitive period of territory establishment of birds which not only investigate low disturbance levels, but which also exclude the effect of habitat modification (e.g. walking trails) are lacking. Here, we experimentally disturbed birds in forest plots by walking through twice a day during territory establishment. Later we compared the breeding bird community of experimentally disturbed plots with that of undisturbed control plots. We discovered that the number of territories (-15.0%) and species richness (-15.2%) in disturbed plots were substantially reduced compared with control plots. Species most affected included those sensitive to human presence (assessed by flight-initiation distances), open-cup nesters and above-ground foragers. Long-distance migrants, however, were unaffected due to their arrival after experimental disturbance took place. These findings highlight how territory establishment is a sensitive period for birds, when even low levels of human recreation may be perceived as threatening, and alter settlement decisions. This can have important implications for the conservation of species, which might go unnoticed when focusing only on already established birds. © 2017 The Author(s).

  4. Experimental models of testicular development and function using human tissue and cells

    DEFF Research Database (Denmark)

    Tharmalingam, Melissa D; Jorgensen, Anne; Mitchell, Rod T

    2018-01-01

    . In this review, we outline experimental approaches used to sustain cells and tissue from human testis at different developmental time-points and discuss relevant end-points. These include survival, proliferation and differentiation of cell lineages within the testis as well as autocrine, paracrine and endocrine...

  5. Involvement of Connective Tissue Growth Factor in Human and Experimental Hypertensive Nephrosclerosis

    NARCIS (Netherlands)

    Ito, Yasuhiko; Aten, Jan; Nguyen, Tri Q.; Joles, Jaap A.; Matsuo, Seiichi; Weening, Jan J.; Goldschmeding, Roel

    2011-01-01

    Background/Aims: Connective tissue growth factor (CTGF; CCN2) has been implicated as a marker and mediator of fibrosis in human and experimental renal disease. Methods: We performed a comparative analysis of CTGF expression in hypertensive patients with and without nephrosclerosis, and in

  6. Effect of acupuncture on the pain perception thresholds of human teeth

    DEFF Research Database (Denmark)

    Bakke, Merete

    1976-01-01

    at intervals of 15 min without acupuncture (1), with acupuncture performed manually (2) and electrically (3), and during electrical stimulation with surface electrodes over acupuncture points (4). On separate days acupuncture and surface stimulation was applied unilaterally at the points S2 (cheek), Li4 (hand......), or S44 (foot). Compared with control threshold (8.44 muA) acupuncture was accompanied by a small increase, most pronounced after 45 min (1.51 muA, P less than 0.0005). However, the hypalgesia observed was insufficient to justify acupuncture as a means of pain control in conservative dentistry....

  7. Eating frequency, food intake, and weight: a systematic review of human and animal experimental studies

    Directory of Open Access Journals (Sweden)

    Hollie eRaynor

    2015-12-01

    Full Text Available Eating frequently during the day, or grazing, has been proposed to assist with managing food intake and weight. This systematic review assessed the effect of greater eating frequency (EF on intake and anthropometrics in human and animal experimental studies. Studies were identified through the PubMed electronic database. To be included, studies needed to be conducted in controlled settings or use methods that carefully monitored food intake, and measure food intake or anthropometrics. Studies using human or animal models of disease states (i.e., conditions influencing glucose or lipid metabolism, aside from being overweight or obese, were not included. The 25 reviewed studies (15 human and 10 animal studies contained varying study designs, EF manipulations (1 to 24 eating occasions per day, lengths of experimentation (230 min to 28 weeks, and sample sizes (3 to 56 participants/animals per condition. Studies were organized into four categories for reporting results: 1 human studies conducted in laboratory/metabolic ward settings; 2 human studies conducted in field settings; 3 animal studies with experimental periods 1 month. Out of the 13 studies reporting on consumption, 8 (61.5% found no significant effect of EF. Seventeen studies reported on anthropometrics, with 11 studies (64.7% finding no significant effect of EF. Future, adequately powered, studies should examine if other factors (i.e., disease states, physical activity, energy balance and weight status, long-term increased EF influence the relationship between increased EF and intake and/or anthropometrics.

  8. The biologic effects of grounding the human body during sleep as measured by cortisol levels and subjective reporting of sleep, pain, and stress.

    Science.gov (United States)

    Ghaly, Maurice; Teplitz, Dale

    2004-10-01

    Diurnal cortisol secretion levels were measured and circadian cortisol profiles were evaluated in a pilot study conducted to test the hypothesis that grounding the human body to earth during sleep will result in quantifiable changes in cortisol. It was also hypothesized that grounding the human body would result in changes in sleep, pain, and stress (anxiety, depression, irritability), as measured by subjective reporting. Twelve (12) subjects with complaints of sleep dysfunction, pain, and stress were grounded to earth during sleep for 8 weeks in their own beds using a conductive mattress pad. Saliva tests were administered to establish pregrounding baseline cortisol levels. Levels were obtained at 4-hour intervals for a 24-hour period to determine the circadian cortisol profile. Cortisol testing was repeated at week 6. Subjective symptoms of sleep dysfunction, pain, and stress were reported daily throughout the 8-week test period. Measurable improvements in diurnal cortisol profiles were observed, with cortisol levels significantly reduced during night-time sleep. Subjects' 24-hour circadian cortisol profiles showed a trend toward normalization. Subjectively reported symptoms, including sleep dysfunction, pain, and stress, were reduced or eliminated in nearly all subjects. Results indicate that grounding the human body to earth ("earthing") during sleep reduces night-time levels of cortisol and resynchronizes cortisol hormone secretion more in alignment with the natural 24-hour circadian rhythm profile. Changes were most apparent in females. Furthermore, subjective reporting indicates that grounding the human body to earth during sleep improves sleep and reduces pain and stress.

  9. A Review on Human Body Communication: Signal Propagation Model, Communication Performance, and Experimental Issues

    Directory of Open Access Journals (Sweden)

    Jian Feng Zhao

    2017-01-01

    Full Text Available Human body communication (HBC, which uses the human body tissue as the transmission medium to transmit health informatics, serves as a promising physical layer solution for the body area network (BAN. The human centric nature of HBC offers an innovative method to transfer the healthcare data, whose transmission requires low interference and reliable data link. Therefore, the deployment of HBC system obtaining good communication performance is required. In this regard, a tutorial review on the important issues related to HBC data transmission such as signal propagation model, channel characteristics, communication performance, and experimental considerations is conducted. In this work, the development of HBC and its first attempts are firstly reviewed. Then a survey on the signal propagation models is introduced. Based on these models, the channel characteristics are summarized; the communication performance and selection of transmission parameters are also investigated. Moreover, the experimental issues, such as electrodes and grounding strategies, are also discussed. Finally, the recommended future studies are provided.

  10. A Protocol of Manual Tests to Measure Sensation and Pain in Humans.

    Science.gov (United States)

    Kostek, Matthew; Polaski, Anna; Kolber, Benedict; Ramsey, Austin; Kranjec, Alexander; Szucs, Kimberly

    2016-12-19

    Numerous qualitative and quantitative techniques can be used to test sensory nerves and pain in both research and clinical settings. The current study demonstrates a quantitative sensory testing protocol using techniques to measure tactile sensation and pain threshold for pressure and heat using portable and easily accessed equipment. These techniques and equipment are ideal for new laboratories and clinics where cost is a concern or a limiting factor. We demonstrate measurement techniques for the following: cutaneous mechanical sensitivity on the arms and legs (von-Frey filaments), radiant and contact heat sensitivity (with both threshold and qualitative assessments using the Visual Analog Scale (VAS)), and mechanical pressure sensitivity (algometer, with both threshold and the VAS). The techniques and equipment described and demonstrated here can be easily purchased, stored, and transported by most clinics and research laboratories around the world. A limitation of this approach is a lack of automation or computer control. Thus, these processes can be more labor intensive in terms of personnel training and data recording than the more sophisticated equipment. We provide a set of reliability data for the demonstrated techniques. From our description, a new laboratory should be able to set up and run these tests and to develop their own internal reliability data.

  11. Muscle tension increases impact force but decreases energy absorption and pain during visco-elastic impacts to human thighs.

    Science.gov (United States)

    Tsui, Felix; Pain, Matthew T G

    2018-01-23

    Despite uncertainty of its exact role, muscle tension has shown an ability to alter human biomechanical response and may have the ability to reduce impact injury severity. The aim of this study was to examine the effects of muscle tension on human impact response in terms of force and energy absorbed and the subjects' perceptions of pain. Seven male martial artists had a 3.9 kg medicine ball dropped vertically from seven different heights, 1.0-1.6 m in equal increments, onto their right thigh. Subjects were instructed to either relax or tense the quadriceps via knee extension (≥60% MVC) prior to each impact. F-scan pressure insoles sampling at 500 Hz recorded impact force and video was recorded at 1000 Hz to determine energy loss from the medicine ball during impact. Across all impacts force was 11% higher, energy absorption was 15% lower and time to peak force was 11% lower whilst perceived impact intensity was significantly lower when tensed. Whether muscle is tensed or not had a significant and meaningful effect on perceived discomfort. However, it did not relate to impact force between conditions and so tensing may alter localised injury risk during human on human type impacts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Effects of a Pain Catastrophizing Induction on Sensory Testing in Women with Chronic Low Back Pain: A Pilot Study

    OpenAIRE

    Taub, Chloe J.; Sturgeon, John A.; Johnson, Kevin A.; Mackey, Sean C.; Darnall, Beth D.

    2017-01-01

    Pain catastrophizing, a pattern of negative cognitive-emotional responses to actual or anticipated pain, maintains chronic pain and undermines response to treatments. Currently, precisely how pain catastrophizing influences pain processing is not well understood. In experimental settings, pain catastrophizing has been associated with amplified pain processing. This study sought to clarify pain processing mechanisms via experimental induction of pain catastrophizing. Forty women with chronic l...

  13. DRG Voltage-Gated Sodium Channel 1.7 Is Upregulated in Paclitaxel-Induced Neuropathy in Rats and in Humans with Neuropathic Pain.

    Science.gov (United States)

    Li, Yan; North, Robert Y; Rhines, Laurence D; Tatsui, Claudio Esteves; Rao, Ganesh; Edwards, Denaya D; Cassidy, Ryan M; Harrison, Daniel S; Johansson, Caj A; Zhang, Hongmei; Dougherty, Patrick M

    2018-01-31

    Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect experienced by cancer patients receiving treatment with paclitaxel. The voltage-gated sodium channel 1.7 (Na v 1.7) plays an important role in multiple preclinical models of neuropathic pain and in inherited human pain phenotypes, and its gene expression is increased in dorsal root ganglia (DRGs) of paclitaxel-treated rats. Hence, the potential of change in the expression and function of Na v 1.7 protein in DRGs from male rats with paclitaxel-related CIPN and from male and female humans with cancer-related neuropathic pain was tested here. Double immunofluorescence in CIPN rats showed that Na v 1.7 was upregulated in small DRG neuron somata, especially those also expressing calcitonin gene-related peptide (CGRP), and in central processes of these cells in the superficial spinal dorsal horn. Whole-cell patch-clamp recordings in rat DRG neurons revealed that paclitaxel induced an enhancement of ProTx II (a selective Na v 1.7 channel blocker)-sensitive sodium currents. Bath-applied ProTx II suppressed spontaneous action potentials in DRG neurons occurring in rats with CIPN, while intrathecal injection of ProTx II significantly attenuated behavioral signs of CIPN. Complementarily, DRG neurons isolated from segments where patients had a history of neuropathic pain also showed electrophysiological and immunofluorescence results indicating an increased expression of Na v 1.7 associated with spontaneous activity. Na v 1.7 was also colocalized in human cells expressing transient receptor potential vanilloid 1 and CGRP. Furthermore, ProTx II decreased firing frequency in human DRGs with spontaneous action potentials. This study suggests that Na v 1.7 may provide a potential new target for the treatment of neuropathic pain, including chemotherapy (paclitaxel)-induced neuropathic pain. SIGNIFICANCE STATEMENT This work demonstrates that the expression and function of the voltage-gated sodium channel Na

  14. Transplanted Human Stem Cell-Derived Interneuron Precursors Mitigate Mouse Bladder Dysfunction and Central Neuropathic Pain after Spinal Cord Injury.

    Science.gov (United States)

    Fandel, Thomas M; Trivedi, Alpa; Nicholas, Cory R; Zhang, Haoqian; Chen, Jiadong; Martinez, Aida F; Noble-Haeusslein, Linda J; Kriegstein, Arnold R

    2016-10-06

    Neuropathic pain and bladder dysfunction represent significant quality-of-life issues for many spinal cord injury patients. Loss of GABAergic tone in the injured spinal cord may contribute to the emergence of these symptoms. Previous studies have shown that transplantation of rodent inhibitory interneuron precursors from the medial ganglionic eminence (MGE) enhances GABAergic signaling in the brain and spinal cord. Here we look at whether transplanted MGE-like cells derived from human embryonic stem cells (hESC-MGEs) can mitigate the pathological effects of spinal cord injury. We find that 6 months after transplantation into injured mouse spinal cords, hESC-MGEs differentiate into GABAergic neuron subtypes and receive synaptic inputs, suggesting functional integration into host spinal cord. Moreover, the transplanted animals show improved bladder function and mitigation of pain-related symptoms. Our results therefore suggest that this approach may be a valuable strategy for ameliorating the adverse effects of spinal cord injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Postural Responses to a Suddenly Released Pulling Force in Older Adults with Chronic Low Back Pain: An Experimental Study.

    Directory of Open Access Journals (Sweden)

    Pei-Yun Lee

    Full Text Available Chronic low back pain (CLBP, one of the most common musculoskeletal conditions in older adults, might affect balance and functional independence. The purpose of this study was to investigate the postural responses to a suddenly released pulling force in older adults with and without CLBP. Thirty community-dwelling older adults with CLBP and 26 voluntary controls without CLBP were enrolled. Participants were required to stand on a force platform while, with one hand, they pulled a string that was fastened at the other end to a 2-kg or to a 4-kg force in the opposite direction at a random order. The number of times the participants lost their balance and motions of center of pressure (COP when the string was suddenly released were recorded. The results demonstrated that although the loss of balance rates for each pulling force condition did not differ between groups, older adults with CLBP had poorer postural responses: delayed reaction, larger displacement, higher velocity, longer path length, and greater COP sway area compared to the older controls. Furthermore, both groups showed larger postural responses in the 4-kg pulling force condition. Although aging is generally believed to be associated with declining balance and postural control, these findings highlight the effect of CLBP on reactive balance when responding to an externally generated force in an older population. This study also suggests that, for older adults with CLBP, in addition to treating them for pain and disability, reactive balance evaluation and training, such as reaction and movement strategy training should be included in their interventions. Clinicians and older patients with CLBP need to be made aware of the significance of impaired reactive balance and the increased risk of falls when encountering unexpected perturbations.

  16. An Experimental Study of Muscle Coordination and Function during Human Locomotion

    Directory of Open Access Journals (Sweden)

    Hirai Hiroaki

    2011-12-01

    Full Text Available How humans solve the ill-posed problem of motor control is still a mystery. In this paper, we attempt to decompose human walking and running as the main movements of a leg into units of motor function. We introduce the key concept of “A-A ratio,” defined as the ratio of an extensor muscle’s electromyography (EMG signal to the sum of agonist and antagonist muscles’ EMG signals. Human walking and running are then decomposed into two units of motor function by applying Principal Component Analysis (PCA to the A-A ratio dataset. The kinematic meanings of these units are also experimentally shown by using a human-like musculoskeletal leg robot.

  17. THE BEACH AND THE LABYRINTH: EXPERIMENTAL URBAN LANDSCAPES OF THE HUMAN (DARK CITY, 1998

    Directory of Open Access Journals (Sweden)

    Vidal, Fernando

    2015-06-01

    Full Text Available In Dark City (Alex Proyas, 1998, people live in a city that is constantly in the dark. The city is in fact a laboratory constructed by a race of Strangers who live below the urban surface to do experiments aimed at discovering what makes human beings human. The Strangers will survive only by becoming like them. To find out what humanity is, but assuming it is essentially related to memory, every day they paralyze all human activity, extract memories from individuals, mix them, and inject them back. When people wake up, they are totally different persons – but do not know it. This article examines how, starting with such a situation, Dark City explores the role of memory in personhood, the problem of authenticity, and the status of “false” memories in making the self, and how the connect to the experimental psychology and the neuroscience of memory.

  18. Pain emotion and homeostasis.

    Science.gov (United States)

    Panerai, Alberto E

    2011-05-01

    Pain has always been considered as part of a defensive strategy, whose specific role is to signal an immediate, active danger. This definition partially fits acute pain, but certainly not chronic pain, that is maintained also in the absence of an active noxa or danger and that nowadays is considered a disease by itself. Moreover, acute pain is not only an automatic alerting system, but its severity and characteristics can change depending on the surrounding environment. The affective, emotional components of pain have been and are the object of extensive attention and research by psychologists, philosophers, physiologists and also pharmacologists. Pain itself can be considered to share the same genesis as emotions and as a specific emotion in contributing to the maintenance of the homeostasis of each unique subject. Interestingly, this role of pain reaches its maximal development in the human; some even argue that it is specific for the human primate.

  19. Doubling Your Payoff: Winning Pain Relief Engages Endogenous Pain Inhibition

    Science.gov (United States)

    Becker, Susanne; Gandhi, Wiebke; Kwan, Saskia; Ahmed, Alysha-Karima; Schweinhardt, Petra

    2015-01-01

    When in pain, pain relief is much sought after, particularly for individuals with chronic pain. In analogy to augmentation of the hedonic experience ("liking") of a reward by the motivation to obtain a reward ("wanting"), the seeking of pain relief in a motivated state might increase the experience of pain relief when obtained. We tested this hypothesis in a psychophysical experiment in healthy human subjects, by assessing potential pain-inhibitory effects of pain relief "won" in a wheel of fortune game compared with pain relief without winning, exploiting the fact that the mere chance of winning induces a motivated state. The results show pain-inhibitory effects of pain relief obtained by winning in behaviorally assessed pain perception and ratings of pain intensity. Further, the higher participants scored on the personality trait novelty seeking, the more pain inhibition was induced. These results provide evidence that pain relief, when obtained in a motivated state, engages endogenous pain-inhibitory systems beyond the pain reduction that underlies the relief in the first place. Consequently, such pain relief might be used to improve behavioral pain therapy, inducing a positive, perhaps self-amplifying feedback loop of reduced pain and improved functionality.

  20. Explicit episodic memory for sensory-discriminative components of capsaicin-induced pain: immediate and delayed ratings.

    Science.gov (United States)

    Jantsch, H H F; Gawlitza, M; Geber, C; Baumgärtner, U; Krämer, H H; Magerl, W; Treede, R D; Birklein, F

    2009-05-01

    Pain memory is thought to affect future pain sensitivity and thus contribute to clinical pain conditions. Systematic investigations of the human capacity to remember sensory features of experimental pain are sparse. In order to address long-term pain memory, nine healthy male volunteers received intradermal injections of three doses of capsaicin (0.05, 1 and 20 microg, separated by 15 min breaks), each given three times in a balanced design across three sessions at one week intervals. Pain rating was performed using a computerized visual analogue scale (0-100) digitized at 1/s, either immediately online or one hour or one day after injection. Subjects also recalled their pains one week later. Capsaicin injection reliably induced a dose-dependent flare (pmemory traces. These results indicate a reliable memory for magnitude and duration of experimentally induced pain. The data further suggest that the consolidation of this memory is an important interim stage, and may take up to one day.

  1. Evaluation of P-glycoprotein expression in pain relevant tissues: understanding translation of efflux from preclinical species to human

    Directory of Open Access Journals (Sweden)

    Renu Singh Dhanikula

    2016-10-01

    Full Text Available Various efflux transporters, such as P-glycoprotein (P-gp are now widely accepted to have profound influence on the disposition of substrates. Nevertheless, there is paucity of information about their expression and functionality in the pain relevant tissues (such as brain, spinal cord and dorsal root ganglia (DRG across various species. Therefore, our attempts were directed at evaluating P-gp expression in these tissues to understand its effect on the central nervous system (CNS disposition. As a means of characterizing the normal tissue distribution of P-gp, immunohistochemistry was performed with two antibodies (C219 and H241 directed against different epitopes of MDR1 gene. Notable expression of P-gp was detected in the DRG of Sprague Dawley rat, Beagle Dog, Cynomolgous monkey as well as human. The expression of P-gp was observed in the CNS tissues with evident species differences, the expression of P-gp in human brain and spinal cord was lower than in rats and dogs but relatively comparable to that in monkeys. However, no species related differences were seen in the expression at the DRG level. Double-labelling using an antibody against a marker of endothelial cells confirmed that P-gp was exclusively localized in capillary endothelial cells. This study highlights the cross species similarities and differences in the expression of P-gp and thus serves as a vital step in understanding the translation of exposure of P-gp substrates to human.

  2. A review of heat transfer in human tooth--experimental characterization and mathematical modeling.

    Science.gov (United States)

    Lin, Min; Xu, Feng; Lu, Tian Jian; Bai, Bo Feng

    2010-06-01

    With rapid advances in modern dentistry, high-energy output instruments (e.g., dental lasers and light polymerizing units) are increasingly employed in dental surgery for applications such as laser assisted tooth ablation, bleaching, hypersensitivity treatment and polymerization of dental restorative materials. Extreme high temperature occurs within the tooth during these treatments, which may induce tooth thermal pain (TTP) sensation. Despite the wide application of these dental treatments, the underlying mechanisms are far from clear. Therefore, there is an urgent need to better understand heat transfer (HT) process in tooth, thermally induced damage of tooth, and the corresponding TTP. This will enhance the design and optimization of clinical treatment strategies. This paper presents the state-of-the-art of the current understanding on HT in tooth, with both experimental study and mathematical modeling reviewed. Limitations of the current experimental and mathematical methodologies are discussed and potential solutions are suggested. Interpretation of TTP in terms of thermally stimulated dentinal fluid flow is also discussed. Copyright (c) 2010 Academy of Dental Materials. All rights reserved.

  3. Experimental studies on the radiosensitizing agents against cultured human glioblastoma and human neurinoma

    International Nuclear Information System (INIS)

    Sawatari, Yutaka

    1976-01-01

    The radiosensitivity increasing effect of bromo-2'-deoxyuridine (BUdR) and 5-fluorouracil (5-FU), alone and in combination, was studied comparatively using tissue culture of brain tumor cells (No. 60 cells originating in human glioblastoma and N cells originating in human neurinoma) with colony formation and growth curve as the quantitative indices and the phase contrast microscope and scanning electron microscope for morphological observation. The inhibitive effect of BUdR on growth of the N cells was above 4μg/ml, while 3000μg/ml was required in the case of the No. 60 cells. This indicates that there is a large difference between the sensitivities of these two cell types against BUdR. Increased sensitivity can be anticipated by pretreatment of the No. 60 cells or the N cells with BUdR with a dose of no growth inhibition effect. N cells have a lower radiosensitivity than No. 60 cells; but when both cells are pretreated with BUdR, N cells have a higher radiosensitivity than No. 60 cells. This increasing radiosensitivity of the N cells, which is clinically benign, suggests the possibility of wider application for radiotherapy in the future. A dose of 2μg/ml of 5-FU alone showed no growth inhibiting effect on either the N cells or the No. 60 cells, but it intensified the effect of BUdR. Using a phase contrast microscope and a scanning electron microscope for morphological observation of the No. 60 cells and the N cells which had been exposed to BUdR+5-FU+X-ray, unique findings were observed on the surface structures of these two kinds of cells. (J.P.N.)

  4. Human psychophysics and rodent spinal neurones exhibit peripheral and central mechanisms of inflammatory pain in the UVB and UVB heat rekindling models.

    Science.gov (United States)

    O'Neill, Jessica; Sikandar, Shafaq; McMahon, Stephen B; Dickenson, Anthony H

    2015-09-01

    Translational research is key to bridging the gaps between preclinical findings and the patients, and a translational model of inflammatory pain will ideally induce both peripheral and central sensitisation, more effectively mimicking clinical pathophysiology in some chronic inflammatory conditions. We conducted a parallel investigation of two models of inflammatory pain, using ultraviolet B (UVB) irradiation alone and UVB irradiation with heat rekindling. We used rodent electrophysiology and human quantitative sensory testing to characterise nociceptive processing in the peripheral and central nervous systems in both models. In both species, UVB irradiation produces peripheral sensitisation measured as augmented evoked activity of rat dorsal horn neurones and increased perceptual responses of human subjects to mechanical and thermal stimuli. In both species, UVB with heat rekindling produces central sensitisation. UVB irradiation alone and UVB with heat rekindling are translational models of inflammation that produce peripheral and central sensitisation, respectively. The predictive value of laboratory models for human pain processing is crucial for improving translational research. The discrepancy between peripheral and central mechanisms of pain is an important consideration for drug targets, and here we describe two models of inflammatory pain that involve ultraviolet B (UVB) irradiation, which can employ peripheral and central sensitisation to produce mechanical and thermal hyperalgesia in rats and humans. We use electrophysiology in rats to measure the mechanically- and thermally-evoked activity of rat spinal neurones and quantitative sensory testing to assess human psychophysical responses to mechanical and thermal stimulation in a model of UVB irradiation and in a model of UVB irradiation with heat rekindling. Our results demonstrate peripheral sensitisation in both species driven by UVB irradiation, with a clear mechanical and thermal hypersensitivity of

  5. An experimental and computational framework to build a dynamic protein atlas of human cell division

    OpenAIRE

    Kavur, Marina; Kavur, Marina; Kavur, Marina; Ellenberg, Jan; Peters, Jan-Michael; Ladurner, Rene; Martinic, Marina; Kueblbeck, Moritz; Nijmeijer, Bianca; Wachsmuth, Malte; Koch, Birgit; Walther, Nike; Politi, Antonio; Heriche, Jean-Karim; Hossain, M.

    2017-01-01

    Essential biological functions of human cells, such as division, require the tight coordination of the activity of hundreds of proteins in space and time. While live cell imaging is a powerful tool to study the distribution and dynamics of individual proteins after fluorescence tagging, it has not yet been used to map protein networks due to the lack of systematic and quantitative experimental and computational approaches. Using the cell and nuclear boundaries as landmarks, we generated a 4D ...

  6. Modeling Human Nonalcoholic Steatohepatitis-Associated Changes in Drug Transporter Expression Using Experimental Rodent Models

    OpenAIRE

    Canet, Mark J.; Hardwick, Rhiannon N.; Lake, April D.; Dzierlenga, Anika L.; Clarke, John D.; Cherrington, Nathan J.

    2014-01-01

    Nonalcoholic fatty liver disease is a prevalent form of chronic liver disease that can progress to the more advanced stage of nonalcoholic steatohepatitis (NASH). NASH has been shown to alter drug transporter regulation and may have implications in the development of adverse drug reactions. Several experimental rodent models have been proposed for the study of NASH, but no single model fully recapitulates all aspects of the human disease. The purpose of the current study was to determine whic...

  7. From meta-omics to causality: experimental models for human microbiome research.

    Science.gov (United States)

    Fritz, Joëlle V; Desai, Mahesh S; Shah, Pranjul; Schneider, Jochen G; Wilmes, Paul

    2013-05-03

    Large-scale 'meta-omic' projects are greatly advancing our knowledge of the human microbiome and its specific role in governing health and disease states. A myriad of ongoing studies aim at identifying links between microbial community disequilibria (dysbiosis) and human diseases. However, due to the inherent complexity and heterogeneity of the human microbiome, cross-sectional, case-control and longitudinal studies may not have enough statistical power to allow causation to be deduced from patterns of association between variables in high-resolution omic datasets. Therefore, to move beyond reliance on the empirical method, experiments are critical. For these, robust experimental models are required that allow the systematic manipulation of variables to test the multitude of hypotheses, which arise from high-throughput molecular studies. Particularly promising in this respect are microfluidics-based in vitro co-culture systems, which allow high-throughput first-pass experiments aimed at proving cause-and-effect relationships prior to testing of hypotheses in animal models. This review focuses on widely used in vivo, in vitro, ex vivo and in silico approaches to study host-microbial community interactions. Such systems, either used in isolation or in a combinatory experimental approach, will allow systematic investigations of the impact of microbes on the health and disease of the human host. All the currently available models present pros and cons, which are described and discussed. Moreover, suggestions are made on how to develop future experimental models that not only allow the study of host-microbiota interactions but are also amenable to high-throughput experimentation.

  8. Chronic Pain

    Science.gov (United States)

    ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. × ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. ...

  9. Experimental and natural infections in MyD88- and IRAK-4-deficient mice and humans

    Science.gov (United States)

    von Bernuth, Horst; Picard, Capucine; Puel, Anne; Casanova, Jean-Laurent

    2013-01-01

    Most Toll-like-receptors (TLRs) and interleukin-1 receptors (IL-1Rs) signal via myeloid differentiation primary response 88 (MyD88) and interleukin-1 receptor-associated kinase 4 (IRAK-4). The combined roles of these two receptor families in the course of experimental infections have been assessed in MyD88- and IRAK-4-deficient mice for almost fifteen years. These animals have been shown to be susceptible to 46 pathogens: 27 bacteria, 8 viruses, 7 parasites, and 4 fungi. Humans with inborn MyD88 or IRAK-4 deficiency were first identified in 2003. They suffer from naturally occurring life-threatening infections caused by a small number of bacterial species, although the incidence and severity of these infections decrease with age. Mouse TLR- and IL-1R-dependent immunity mediated by MyD88 and IRAK-4 seems to be vital to combat a wide array of experimentally administered pathogens at most ages. By contrast, human TLR- and IL-1R-dependent immunity mediated by MyD88 and IRAK-4 seems to be effective in the natural setting against only a few bacteria and is most important in infancy and early childhood. The roles of TLRs and IL-1Rs in protective immunity deduced from studies in mutant mice subjected to experimental infections should therefore be reconsidered in the light of findings for natural infections in humans carrying mutations as discussed in this review. PMID:23255009

  10. Human papillomavirus vaccines, complex regional pain syndrome, postural orthostatic tachycardia syndrome, and autonomic dysfunction - a review of the regulatory evidence from the European Medicines Agency

    DEFF Research Database (Denmark)

    Jefferson, Tom; Jørgensen, Lars

    2017-01-01

    Recent concerns about a possible association between exposure of young women to human papillomavirus (HPV) vaccines and two "dysautonomic syndromes" (a collection of signs and symptoms thought to be caused by autoimmunity) - complex regional pain syndrome (CRPS) and postural orthostatic tachycardia...

  11. A Novel Magnetic Stimulator Increases Experimental Pain Tolerance in Healthy Volunteers : A Double-Blind Sham-Controlled Crossover Study

    NARCIS (Netherlands)

    Kortekaas, R.; van Nierop, L.E.; Baas, V.G.; Konopka, K.H.; Harbers, M.; van der Hoeven, J.H.; van Wijhe, M.; Aleman, A.; Maurits, N.M.

    2013-01-01

    The 'complex neural pulse'(TM) (CNP) is a neuromodulation protocol employing weak pulsed electromagnetic fields (PEMF). A pioneering paper reported an analgesic effect in healthy humans after 30 minutes of CNP-stimulation using three nested whole head coils. We aimed to devise and validate a

  12. Characterizing human stem cell-derived sensory neurons at the single-cell level reveals their ion channel expression and utility in pain research.

    Science.gov (United States)

    Young, Gareth T; Gutteridge, Alex; Fox, Heather DE; Wilbrey, Anna L; Cao, Lishuang; Cho, Lily T; Brown, Adam R; Benn, Caroline L; Kammonen, Laura R; Friedman, Julia H; Bictash, Magda; Whiting, Paul; Bilsland, James G; Stevens, Edward B

    2014-08-01

    The generation of human sensory neurons by directed differentiation of pluripotent stem cells opens new opportunities for investigating the biology of pain. The inability to generate this cell type has meant that up until now their study has been reliant on the use of rodent models. Here, we use a combination of population and single-cell techniques to perform a detailed molecular, electrophysiological, and pharmacological phenotyping of sensory neurons derived from human embryonic stem cells. We describe the evolution of cell populations over 6 weeks of directed differentiation; a process that results in the generation of a largely homogeneous population of neurons that are both molecularly and functionally comparable to human sensory neurons derived from mature dorsal root ganglia. This work opens the prospect of using pluripotent stem-cell-derived sensory neurons to study human neuronal physiology and as in vitro models for drug discovery in pain and sensory disorders.

  13. Characterizing Human Stem Cell–derived Sensory Neurons at the Single-cell Level Reveals Their Ion Channel Expression and Utility in Pain Research

    Science.gov (United States)

    Young, Gareth T; Gutteridge, Alex; Fox, Heather DE; Wilbrey, Anna L; Cao, Lishuang; Cho, Lily T; Brown, Adam R; Benn, Caroline L; Kammonen, Laura R; Friedman, Julia H; Bictash, Magda; Whiting, Paul; Bilsland, James G; Stevens, Edward B

    2014-01-01

    The generation of human sensory neurons by directed differentiation of pluripotent stem cells opens new opportunities for investigating the biology of pain. The inability to generate this cell type has meant that up until now their study has been reliant on the use of rodent models. Here, we use a combination of population and single-cell techniques to perform a detailed molecular, electrophysiological, and pharmacological phenotyping of sensory neurons derived from human embryonic stem cells. We describe the evolution of cell populations over 6 weeks of directed differentiation; a process that results in the generation of a largely homogeneous population of neurons that are both molecularly and functionally comparable to human sensory neurons derived from mature dorsal root ganglia. This work opens the prospect of using pluripotent stem-cell–derived sensory neurons to study human neuronal physiology and as in vitro models for drug discovery in pain and sensory disorders. PMID:24832007

  14. The analgesic effect of diclofenac sodium administered via the epidural route in an experimental visceral pain model.

    Science.gov (United States)

    Kilci, O; Demir, T; Günbey, M; Kara, C; Bayazit, D; Ornek, D; Baydar, M

    2016-01-01

    The aim of this study was to investigate the characteristics of the analgesic effect of diclofenac sodium injected epidurally in single or repeated doses and whether tolerance develops in long-term use. A total of 30 rats were included in the study. The rats were anesthetized using intraperitoneal ketamine hydrochloride and an epidural catheter (EC) was inserted at the level of 13th dorsal thoraco-lumbar vertebrae (T13). Eleven rats were excluded from the study. The remaining 19 rats were randomly divided into three groups; Group Control (Group C) (n = 6) received 20 μL normal saline solution (NS) via EC for 10 days; Group Single Dose (Group SD) (n = 6) received 20 μL NS for 9 days and 6 μg diclofenac via EC on 10th day; Group Ten Doses (Group TDs) (n = 7) received 6 μg diclofenac via EC in 20 μL NS for 10 days. On the 10th day, 30 min after epidural diclofenac sodium, 300 mg/kg of 3% acetic acid was injected via intraperitoneal route, and the rats were observed for 30 min and number of writhing reflex (WR) was recorded. The values of total number of Writhing Reflex (WRT) and Writhing reflex per minute(WR/min) were found to be significantly higher in Group C compared with Groups SD and TD (P = 0.009). Single and repeated doses of diclofenac sodium via epidural route have an analgesic effect in a visceral pain model in rats without developing tolerance.

  15. New experimental data on the human dermal absorption of Simazine and Carbendazim help to refine the assessment of human exposure.

    Science.gov (United States)

    Bányiová, Katarína; Nečasová, Anežka; Kohoutek, Jiří; Justan, Ivan; Čupr, Pavel

    2016-02-01

    Due to their widespread usage, people are exposed to pesticides on a daily basis. Although these compounds may have adverse effects on their health, there is a gap in the data and the methodology needed to reliably quantify the risks of non-occupational human dermal exposure to pesticides. We used Franz cells and human skin in order to measure the dermal absorption kinetics (steady-state flux, lag time and permeability coefficient) of Carbendazim and Simazine. These parameters were then used to refine the dermal exposure model and a probabilistic simulation was used to quantify risks resulting from exposure to pesticide-polluted waters. The experimentally derived permeability coefficient was 0.0034 cm h(-1) for Carbendazim and 0.0047 cm h(-1) for Simazine. Two scenarios (varying exposure duration and concentration, i.e. environmentally relevant and maximum solubility) were used to quantify the human health risks (hazard quotients) for Carbendazim and Simazine. While no risks were determined in the case of either scenario, the permeability coefficient, which is concentration independent and donor, formulation, compound and membrane specific, may be used in other scenarios and exposure models to quantify more precisely the dermally absorbed dose during exposure to polluted water. To the best of our knowledge, the dermal absorption kinetics parameters defined here are being published for the first time. The usage of experimental permeability parameters in combination with probabilistic risk assessment thus provides a new tool for quantifying the risks of human dermal exposure to pesticides. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Experimental Determination of the Neutron Radiation-Dose Distribution in the Human Phantom

    Energy Technology Data Exchange (ETDEWEB)

    Stipcic, Neda [Institute Rudjer Bogkovic, Zagreb, Yugoslavia (Serbia)

    1967-01-15

    The quality of the radiation delivering the radiation dose to the human phantom is quite different from that of the incident neutron beam. This paper describes the experimental investigation of the variation of neutron dose related to the variation of neutron fluence with depth in the human phantom. The distribution of neutron radiation was determined in the human phantom - a cube of paraffin wax 25 cm x 25 cm x 50 cm with a density of 0.92 cm{sup -3}. Po-Be and Ra-Be point sources were used as neutron sources. Neutron fluences were measured using different types of detector: scintillation detector, BF{sub 3} counter, and nuclear-track emulsions. Since the fluence measurements with these three types of detectors were carried out under the same experimental conditions, it was possible to separate and analyse each part of the radiation dose in the paraffin. From the investigations, the distribution of the total radiation dose was obtained as a function of the paraffin depth. The maximum value of this dose distribution is constant with respect to the distance between the source and the paraffin phantom. From the results obtained, some conclusions may be drawn concerning the amount of absorbed radiation dose in the human phantom. (author)

  17. The ethics of human volunteer studies involving experimental exposure to pesticides: unanswered dilemmas

    Directory of Open Access Journals (Sweden)

    London Leslie

    2010-08-01

    Full Text Available Abstract The controversy about the use of data from human volunteer studies involving experimental exposure to pesticides as part of regulatory risk assessment has been widely discussed, but the complex and interrelated scientific and ethical issues remain largely unresolved. This discussion paper, generated by authors who comprised a workgroup of the ICOH Scientific Committee on Rural Health, reviews the use of human experimental studies in regulatory risk assessment for pesticides with a view to advancing the debate as to when, if ever, such studies might be ethically justifiable. The discussion is based on three elements: (a a review of discussion papers on the topic of human testing of pesticides and the positions adopted by regulatory agencies in developed countries; (b an analysis of published and unpublished studies involving human testing with pesticides, both in the peer-reviewed literature and in the JMPR database; and (c application of an ethical analysis to the problem. The paper identifies areas of agreement which include general principles that may provide a starting point on which to base criteria for judgements as to the ethical acceptability of such studies. However, the paper also highlights ongoing unresolved differences of opinion inherent in ethical analysis of contentious issues, which we propose should form a starting point for further debate and the development of guidelines to achieve better resolution of this matter.

  18. The ethics of human volunteer studies involving experimental exposure to pesticides: unanswered dilemmas.

    Science.gov (United States)

    London, Leslie; Coggon, David; Moretto, Angelo; Westerholm, Peter; Wilks, Martin F; Colosio, Claudio

    2010-08-18

    The controversy about the use of data from human volunteer studies involving experimental exposure to pesticides as part of regulatory risk assessment has been widely discussed, but the complex and interrelated scientific and ethical issues remain largely unresolved. This discussion paper, generated by authors who comprised a workgroup of the ICOH Scientific Committee on Rural Health, reviews the use of human experimental studies in regulatory risk assessment for pesticides with a view to advancing the debate as to when, if ever, such studies might be ethically justifiable. The discussion is based on three elements: (a) a review of discussion papers on the topic of human testing of pesticides and the positions adopted by regulatory agencies in developed countries; (b) an analysis of published and unpublished studies involving human testing with pesticides, both in the peer-reviewed literature and in the JMPR database; and (c) application of an ethical analysis to the problem. The paper identifies areas of agreement which include general principles that may provide a starting point on which to base criteria for judgements as to the ethical acceptability of such studies. However, the paper also highlights ongoing unresolved differences of opinion inherent in ethical analysis of contentious issues, which we propose should form a starting point for further debate and the development of guidelines to achieve better resolution of this matter.

  19. The ethics of human volunteer studies involving experimental exposure to pesticides: unanswered dilemmas

    Science.gov (United States)

    2010-01-01

    The controversy about the use of data from human volunteer studies involving experimental exposure to pesticides as part of regulatory risk assessment has been widely discussed, but the complex and interrelated scientific and ethical issues remain largely unresolved. This discussion paper, generated by authors who comprised a workgroup of the ICOH Scientific Committee on Rural Health, reviews the use of human experimental studies in regulatory risk assessment for pesticides with a view to advancing the debate as to when, if ever, such studies might be ethically justifiable. The discussion is based on three elements: (a) a review of discussion papers on the topic of human testing of pesticides and the positions adopted by regulatory agencies in developed countries; (b) an analysis of published and unpublished studies involving human testing with pesticides, both in the peer-reviewed literature and in the JMPR database; and (c) application of an ethical analysis to the problem. The paper identifies areas of agreement which include general principles that may provide a starting point on which to base criteria for judgements as to the ethical acceptability of such studies. However, the paper also highlights ongoing unresolved differences of opinion inherent in ethical analysis of contentious issues, which we propose should form a starting point for further debate and the development of guidelines to achieve better resolution of this matter. PMID:20718963

  20. An experimental approach to validating a theory of human error in complex systems

    Science.gov (United States)

    Morris, N. M.; Rouse, W. B.

    1985-01-01

    The problem of 'human error' is pervasive in engineering systems in which the human is involved. In contrast to the common engineering approach of dealing with error probabilistically, the present research seeks to alleviate problems associated with error by gaining a greater understanding of causes and contributing factors from a human information processing perspective. The general approach involves identifying conditions which are hypothesized to contribute to errors, and experimentally creating the conditions in order to verify the hypotheses. The conceptual framework which serves as the basis for this research is discussed briefly, followed by a description of upcoming research. Finally, the potential relevance of this research to design, training, and aiding issues is discussed.

  1. Beagle: an appropriate experimental animal for extrapolating the organ distribution pattern of Th in humans

    International Nuclear Information System (INIS)

    Singh, N.P.; Zimmerman, C.J.; Taylor, G.N.; Wrenn, M.E.

    1988-01-01

    The concentrations and the organ distribution patterns of 228Th, 230Th and 232Th in two 9-y-old dogs of our beagle colony were determined. The dogs were exposed only to background environmental levels of Th isotopes through ingestion (food and water) and inhalation as are humans. The organ distribution patterns of the isotopes in the beagles were compared to the organ distribution patterns in humans to determine if it is appropriate to extrapolate the beagle organ burden data to humans. Among soft tissues, only the lungs, lymph nodes, kidney and liver, and skeleton contained measurable amounts of Th isotopes. The organ distribution pattern of Th isotopes in humans and dog are similar, the majority of Th being in the skeleton of both species. The average skeletal concentrations of 228Th in dogs were 30 to 40 times higher than the average skeletal concentrations of the parent 232Th, whereas the concentration of 228Th in human skeleton was only four to five times higher than 232Th. This suggests that dogs have a higher intake of 228Ra through food than humans. There is a similar trend in the accumulations of 232Th, 230Th and 228Th in the lungs of dog and humans. The percentages of 232Th, 230Th and 228Th in human lungs are 26, 9.7 and 4.8, respectively, compared to 4.2, 2.6 and 0.48, respectively, in dog lungs. The larger percentages of Th isotopes in human lungs may be due simply to the longer life span of humans. If the burdens of Th isotopes in human lungs are normalized to an exposure time of 9.2 y (mean age of dogs at the time of sacrifice), the percent burden of 232Th, 230Th and 228Th in human lungs are estimated to be 3.6, 1.3 and 0.66, respectively. These results suggest that the beagle may be an appropriate experimental animal for extrapolating the organ distribution pattern of Th in humans

  2. Age-Related Features of Reactive Catecholamine Shifts in the Spinal Cord in Acute Somatic Pain: Experimental Study

    Directory of Open Access Journals (Sweden)

    V. G. Ovsyannikov

    2007-01-01

    Full Text Available Objective: to study the age-related features of an adrenergic response of the central nervous system to acute somatic pain (ASP.Subjects and methods: The spinal cord (SC levels of adrenaline (A, noradrenaline (NA, and dopamine (DA were studied in albino male rats of five age groups: 1 neonatal (2—4-day rats; 2 17—18-day rats that began to see; 3 monthly rats; 4 sexually mature (3—4 month ones; and 5 old ones aged over 2 years. ASP was reproduced by electrodermal stimulation of the rat tail; the levels of catecholamines (CA were measured by spectrofluorimetric microassay.Results. During postnatal ontogenesis, the rats were found to have a phase pattern of physiological changes in the spinal concentrations of CA: a decrease in their high neonatal levels (due to DA by the time the animals began to see; their progressive increase by prepuberty (due to NA and in sexually maturity (due to A and DA, and a reduction in all CA fractions in old rats. ASP was attended by a rise in the SC concentration of CA in the neonatal animals and by clearly-cut reactive shifts in all fractions in the old ones. With A and DA increases, the SC concentrations of NA halved in the rats that began to see and had ASP; the amount of CA remained unchanged as compared with the controls. In prepubertal and sexually mature male rats, there was a reduction in the spinal CA pool, but due to different components: to A and NA in 35-day rats and to A and DA in 3-month ones.Conclusion. Age-related changes in the pattern of a spinal CA response in rats with ASP show a ontogenetic trend in the development of adrenal responsiveness from the immature generalized forms of an early postnatal period to the definitive differentiated economic reactions of the hypo-to-normergic type and then to the hyperergic destructive reactions of old age. 

  3. The Effects of Sleep Deprivation on Pain

    Directory of Open Access Journals (Sweden)

    Bernd Kundermann

    2004-01-01

    Full Text Available Chronic pain syndromes are associated with alterations in sleep continuity and sleep architecture. One perspective of this relationship, which has not received much attention to date, is that disturbances of sleep affect pain. To fathom this direction of cause, experimental human and animal studies on the effects of sleep deprivation on pain processing were reviewed. According to the majority of the studies, sleep deprivation produces hyperalgesic changes. Furthermore, sleep deprivation can counteract analgesic effects of pharmacological treatments involving opioidergic and serotoninergic mechanisms of action. The heterogeneity of the human data and the exclusive interest in rapid eye movement sleep deprivation in animals so far do not allow us to draw firm conclusions as to whether the hyperalgesic effects are due to the deprivation of specific sleep stages or whether they result from a generalized disruption of sleep continuity. The significance of opioidergic and serotoninergic processes as mediating mechanisms of the hyperalgesic changes produced by sleep deprivation are discussed.

  4. The effects of patient-professional partnerships on the self-management and health outcomes for patients with chronic back pain : a quasi-experimental study

    OpenAIRE

    Fu, Yu; Yu, Ge; McNichol, Elaine; Marczewski, Kath; Closs, S. José

    2016-01-01

    Background: Self-management may be a lifelong task for patients with chronic back pain. Research suggests that chronic pain self-management programmes have beneficial effects on patients? health outcome. Contemporary pain management theories and models also suggest that a good patient-professional partnership enhances patients? ability to self-manage their condition.

  5. Pain Adaptability in Individuals With Chronic Musculoskeletal Pain Is Not Associated With Conditioned Pain Modulation.

    Science.gov (United States)

    Wan, Dawn Wong Lit; Arendt-Nielsen, Lars; Wang, Kelun; Xue, Charlie Changli; Wang, Yanyi; Zheng, Zhen

    2018-03-27

    Healthy humans can be divided into the pain adaptive (PA) and the pain nonadaptive (PNA) groups; PA showed a greater decrease in pain rating to a cold pressor test (CPT) than PNA. This study examined if the dichotomy of pain adaptability existed in individuals with chronic musculoskeletal pain. CPTs at 2°C and 7°C were used to assess the status of pain adaptability in participants with either chronic nonspecific low back pain or knee osteoarthritis. The participants' potency of conditioned pain modulation (CPM) and local inhibition were measured. The strengths of pain adaptability at both CPTs were highly correlated. PA and PNA did not differ in their demographic characteristics, pain thresholds from thermal and pressure stimuli, or potency of local inhibition or CPM. PA reached their maximum pain faster than PNA (t 41 = -2.76, P adaptability exists in musculoskeletal pain patients. Consistent with the healthy human study, the strength of pain adaptability and potency of CPM are not related. Pain adaptability could be another form of endogenous pain inhibition of which clinical implication is yet to be understood. The dichotomy of pain adaptability was identified in healthy humans. The current study confirms that this dichotomy also exists in individuals with chronic musculoskeletal pain, and could be reliably assessed with CPTs at 2°C and 7°C. Similar to the healthy human study, pain adaptability is not associated with CPM, and may reflect the temporal aspect of pain inhibition. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

  6. Comparison between a Computational Seated Human Model and Experimental Verification Data

    Directory of Open Access Journals (Sweden)

    Christian G. Olesen

    2014-01-01

    Full Text Available Sitting-acquired deep tissue injuries (SADTI are the most serious type of pressure ulcers. In order to investigate the aetiology of SADTI a new approach is under development: a musculo-skeletal model which can predict forces between the chair and the human body at different seated postures. This study focuses on comparing results from a model developed in the AnyBody Modeling System, with data collected from an experimental setup. A chair with force-measuring equipment was developed, an experiment was conducted with three subjects, and the experimental results were compared with the predictions of the computational model. The results show that the model predicted the reaction forces for different chair postures well. The correlation coefficients of how well the experiment and model correlate for the seat angle, backrest angle and footrest height was 0.93, 0.96, and 0.95. The study show a good agreement between experimental data and model prediction of forces between a human body and a chair. The model can in the future be used in designing wheelchairs or automotive seats.

  7. Recombinant human acetylcholine receptor alpha-subunit induces chronic experimental autoimmune myasthenia gravis.

    Science.gov (United States)

    Lennon, V A; Lambert, E H; Leiby, K R; Okarma, T B; Talib, S

    1991-04-01

    A synthetic gene encoding the 210 N-terminal residues of the alpha-subunit of the nicotinic acetylcholine receptor (AChR) of human skeletal muscle was cloned into an inducible expression plasmid to produce a fusion protein in high yield in Escherichia coli. Like native human AChR, the recombinant human alpha 1-210 protein induced AChR-binding, AChR-modulating, and AChR-blocking autoantibodies in rats when injected once intradermally as an emulsion in CFA, with Bordetella pertussis vaccine as supplementary adjuvant. The minimum dose of recombinant protein required to induce biochemical signs of experimental autoimmune myasthenia gravis (EAMG) with 100% incidence was 2.2 micrograms. With 6.6 to 22 micrograms, serum levels of autoantibodies were persistent, and clinically apparent EAMG lasted more than a month. Clinical, electrophysiological, and biochemical indices of EAMG induced by doses of 66 micrograms or more were more uniformly severe and persistent, with 33% fatality. Rats receiving a control extract of E. coli containing plasmid without the alpha 1-210 codon insert, with adjuvants, did not develop autoantibodies or signs of EAMG. This highly reproducible new model of EAMG induced by a recombinant human autoantigen should be valuable for testing Ag-specific immunotherapeutic strategies that might be applicable to treating acquired myasthenia gravis in humans.

  8. Interleukin 1-induced augmentation of experimental metastases from a human melanoma in nude mice

    International Nuclear Information System (INIS)

    Giavazzi, R.; Garofalo, A.; Bani, M.R.; Abbate, M.; Ghezzi, P.; Boraschi, D.; Mantovani, A.; Dejana, E.

    1990-01-01

    This study has examined the effect of the cytokine interleukin 1 (IL-1) on metastasis formation by the human melanoma A375M in nude mice. We have found that human recombinant IL-1 beta (a single injection greater than 0.01 micrograms per mouse i.v. given before tumor cells) induced an augmentation of experimental lung metastases from the A375M tumor cells in nude mice. This effect was rapidly induced and reversible within 24 h after IL-1 injection. A similar effect was induced by human recombinant IL-1 alpha and human recombinant tumor necrosis factor, but not by human recombinant interleukin 6. 5-[125I]odo-2'-deoxyuridine-radiolabeled A375M tumor cells injected i.v. remained at a higher level in the lungs of nude mice receiving IL-1 than in control mice. In addition, IL-1 injected 1 h, but not 24 h, after tumor cells enhanced lung colonization as well, thus suggesting an effect of IL-1 on the vascular transit of tumor cells. These findings may explain the observation of enhanced secondary localization of tumor cells at inflammatory sites and suggest that modulation of secondary spread should be carefully considered when assessing the ability of this cytokine to complement cytoreductive therapies

  9. The biological effects of quadripolar radiofrequency sequential application: a human experimental study.

    Science.gov (United States)

    Nicoletti, Giovanni; Cornaglia, Antonia Icaro; Faga, Angela; Scevola, Silvia

    2014-10-01

    An experimental study was conducted to assess the effectiveness and safety of an innovative quadripolar variable electrode configuration radiofrequency device with objective measurements in an ex vivo and in vivo human experimental model. Nonablative radiofrequency applications are well-established anti-ageing procedures for cosmetic skin tightening. The study was performed in two steps: ex vivo and in vivo assessments. In the ex vivo assessments the radiofrequency applications were performed on human full-thickness skin and subcutaneous tissue specimens harvested during surgery for body contouring. In the in vivo assessments the applications were performed on two volunteer patients scheduled for body contouring surgery at the end of the study. The assessment methods were: clinical examination and medical photography, temperature measurement with thermal imaging scan, and light microscopy histological examination. The ex vivo assessments allowed for identification of the effective safety range for human application. The in vivo assessments allowed for demonstration of the biological effects of sequential radiofrequency applications. After a course of radiofrequency applications, the collagen fibers underwent an immediate heat-induced rearrangement and were partially denaturated and progressively metabolized by the macrophages. An overall thickening and spatial rearrangement was appreciated both in the collagen and elastic fibers, the latter displaying a juvenile reticular pattern. A late onset in the macrophage activation after sequential radiofrequency applications was appreciated. Our data confirm the effectiveness of sequential radiofrequency applications in obtaining attenuation of the skin wrinkles by an overall skin tightening.

  10. Experimental primates and non-human primate (NHP) models of human diseases in China: current status and progress.

    Science.gov (United States)

    Zhang, Xiao-Liang; Pang, Wei; Hu, Xin-Tian; Li, Jia-Li; Yao, Yong-Gang; Zheng, Yong-Tang

    2014-11-18

    Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China's growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China's life sciences and pharmaceutical industry, and enhance China's position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective countermeasures to better utilize NHP resources and further foster NHP research in China.

  11. Experimental identification and analytical modelling of human walking forces: Literature review

    Science.gov (United States)

    Racic, V.; Pavic, A.; Brownjohn, J. M. W.

    2009-09-01

    Dynamic forces induced by humans walking change simultaneously in time and space, being random in nature and varying considerably not only between different people but also for a single individual who cannot repeat two identical steps. Since these important aspects of walking forces have not been adequately researched in the past, the corresponding lack of knowledge has reflected badly on the quality of their mathematical models used in vibration assessments of pedestrian structures such as footbridges, staircases and floors. To develop better force models which can be used with more confidence in the structural design, an adequate experimental and analytical approach must be taken to account for their complexity. This paper is the most comprehensive review published to date, of 270 references dealing with different experimental and analytical characterizations of human walking loading. The source of dynamic human-induced forces is in fact in the body motion. To date, human motion has attracted a lot of interest in many scientific branches, particularly in medical and sports science, bioengineering, robotics, and space flight programs. Other fields include biologists of various kinds, physiologists, anthropologists, computer scientists (graphics and animation), human factors and ergonomists, etc. It resulted in technologically advanced tools that can help understanding the human movement in more detail. Therefore, in addition to traditional direct force measurements utilizing a force plate and an instrumented treadmill, this review also introduces methods for indirect measurement of time-varying records of walking forces via combination of visual motion tracking (imaging) data and known body mass distribution. The review is therefore an interdisciplinary article that bridges the gaps between biomechanics of human gait and civil engineering dynamics. Finally, the key reason for undertaking this review is the fact that human-structure dynamic interaction and

  12. The Mitochondrial Protein Atlas: A Database of Experimentally Verified Information on the Human Mitochondrial Proteome.

    Science.gov (United States)

    Godin, Noa; Eichler, Jerry

    2017-09-01

    Given its central role in various biological systems, as well as its involvement in numerous pathologies, the mitochondrion is one of the best-studied organelles. However, although the mitochondrial genome has been extensively investigated, protein-level information remains partial, and in many cases, hypothetical. The Mitochondrial Protein Atlas (MPA; URL: lifeserv.bgu.ac.il/wb/jeichler/MPA ) is a database that provides a complete, manually curated inventory of only experimentally validated human mitochondrial proteins. The MPA presently contains 911 unique protein entries, each of which is associated with at least one experimentally validated and referenced mitochondrial localization. The MPA also contains experimentally validated and referenced information defining function, structure, involvement in pathologies, interactions with other MPA proteins, as well as the method(s) of analysis used in each instance. Connections to relevant external data sources are offered for each entry, including links to NCBI Gene, PubMed, and Protein Data Bank. The MPA offers a prototype for other information sources that allow for a distinction between what has been confirmed and what remains to be verified experimentally.

  13. Can experimental data in humans verify the finite element-based bone remodeling algorithm?

    DEFF Research Database (Denmark)

    Wong, C.; Gehrchen, P.M.; Kiaer, T.

    2008-01-01

    STUDY DESIGN: A finite element analysis-based bone remodeling study in human was conducted in the lumbar spine operated on with pedicle screws. Bone remodeling results were compared to prospective experimental bone mineral content data of patients operated on with pedicle screws. OBJECTIVE......: The validity of 2 bone remodeling algorithms was evaluated by comparing against prospective bone mineral content measurements. Also, the potential stress shielding effect was examined using the 2 bone remodeling algorithms and the experimental bone mineral data. SUMMARY OF BACKGROUND DATA: In previous studies...... operated on with pedicle screws between L4 and L5. The stress shielding effect was also examined. The bone remodeling results were compared with prospective bone mineral content measurements of 4 patients. They were measured after surgery, 3-, 6- and 12-months postoperatively. RESULTS: After 1 year...

  14. Consumption of an aqueous cyanophyta extract derived from Arthrospira platensis is associated with reduction of chronic pain: results from two human clinical pilot studies

    Directory of Open Access Journals (Sweden)

    Jensen GS

    2016-05-01

    Full Text Available Gitte S Jensen,1 Victoria L Attridge,1 Steve G Carter,1 Jesse Guthrie,2 Axel Ehmann,2 Kathleen F Benson1 1NIS Labs, 2Cerule LLC, Klamath Falls, OR, USA Objectives: The aim of this study was to evaluate the effects of consumption of an aqueous cyanophyta extract (ACE from Arthrospira platensis on chronic pain in humans, in two clinical pilot studies. Design and interventions: The two pilot studies each involved 12 subjects experiencing chronic pain. The initial study followed an open-label 4-week study design involving consumption of 1 g ACE per day. A subsequent placebo-controlled, single-blind, crossover study involved consumption of 500 mg ACE, 250 mg ACE, or 0 mg ACE (placebo per day for 1-week duration, separated by 1-week washout period. Subjects: Adult subjects of both sexes, with chronic joint-related pain for at least 6 months prior to enrollment, were recruited after obtaining written informed consent. Outcome measures: Visual analog scales were used to score pain at rest and during physical activity for each person's primary and secondary areas of chronic pain. An activities of daily living questionnaire was used to collect data on physical functioning. Results: The data showed rapid reduction of chronic pain in people consuming ACE, where the reduction in pain scores for each person's primary pain area reached a high level of statistical significance after 2 weeks of consumption (P<0.01, both when at rest and when being physically active. Secondary pain areas when physically active showed highly significant improvements within 1 week of consumption of 1 g/d (P<0.001 and borderline significant improvements within 1 week of consuming 500 mg/d (P<0.065 and 250 mg/d (P<0.05. This was accompanied by an increased ability to perform daily activities (P<0.05. A small but significant weight loss was observed during the 4-week study, as the average body mass index dropped from 31.4 to 29.4 (P<0.01. Conclusion: Consumption of ACE was associated

  15. [Christian responsibility and experimental medicine. Experiments with and on humans, experiments on animals].

    Science.gov (United States)

    Grosse, Heinrich W

    2002-01-01

    The Jewish-Christian convictions that man was created as the image of God founded the "ethics of unavailability" which contrast with the utilitarian "ethics of interests." As man s nature is imperfect according to biblical understanding, those responsible in the field of experimental medicine should counteract all tendencies in society which promote an utopian definition of health and an eugenic mentality (idea of the "perfection of mankind"). Consequently, scientists must reflect their own image of man and the effects of their actions on this image. The goals of experimental medicine must also be examined under the aspect of fairness: do they only benefit a minority in the rich industrial nations? As in research on humans, the ethical evaluation of animal experiments must consider the question of the underlying image of humanity and the responsibility of mankind connected to it. Because of changes in society's values, the validity of traditional anthropocentrism is increasingly questioned. However, this does not affect the view of the special position of man as the bearer of responsibility. Even though there are different biblical statements on the relationship between man and animal, the Christian maxim to minimise violence towards animals can be derived from them. In the case of animal experiments this means: experiments which cause the animals severe suffering must be avoided by waiving the potential gain of knowledge from them. In general: in an ethical discussion on medical experiments using humans or animals, the public must be informed completely and involved effectively. A moratorium must be possible before plans become facts. Thinking about ethical problems in the area of experimental medicine should not be separated from the far-reaching questions about changes in our lifestyle and consumer behaviour.

  16. Possible analgesic effect of vigabatrin in animal experimental chronic neuropathic pain Possível efeito analgésico da vigabatrina na dor neuropática crônica experimental animal

    Directory of Open Access Journals (Sweden)

    NILZA D. ALVES

    1999-12-01

    Full Text Available Since anticonvulsants have been used for treating neuralgias, an interest has arisen to experimentally test vigabatrin for its gabaergic mechanism of action. For this, 41 Wistar rats were used, and in 25 of them a constrictive sciatic neuropathy was induced (Bennet & Xie model. For testing pain symptoms, spontaneous (scratching and evoked behaviors to noxious (46o C and non-noxious (40o C thermal stimuli were quantified. Moreover, a comparative pharmacological study of vigabatrin with other analgesic anticonvulsant drugs was also performed. The results showed a possible dose-dependent analgesic effect of vigabatrin (gamma-vinyl-GABA on experimental neuropathic pain, as shown by the significant (pO uso de anticonvulsivantes no tratamento de neuralgias despertou um interesse em testar novas drogas anticonvulsivantes, e dentre essas a vigabatrina por possuir mecanismo de ação gabaérgico. Para isso, foram usados 41 ratos Wistar e em 25 deles induziu-se neuropatia ciática constritiva (modelo de Bennett & Xie. Para testar sintomas de dor, foram quantificados comportamentos espontâneos (coçar-se e evocados, por meio de estímulos térmicos nocivos (46oC e não-nocivos (40oC. Além disso, realizou-se estudo comparativo da vigabatrina com outros anticonvulsivantes analgésicos. Os resultados mostraram um possível efeito analgésico, dose-dependente, de vigabatrina (gama-vinil-GABA em dor neuropática experimental. Isso foi evidenciado pela diminuição significativa (p<0,05 do comportamento de coçar-se e pelo aumento significativo (p<0,05 da latência de retirada da pata posterior direita a estímulos térmicos nocivos. Isso foi corroborado por achados semelhantes em experimentos com anticonvulsivantes (carbamazepina, fenitoína e ácido valpróico analgésicos. Esse possível efeito analgésico da vigabatrina (ainda não descrito na literatura não é mediado pelo sistema opióide.

  17. Language and the pain experience.

    Science.gov (United States)

    Wilson, Dianne; Williams, Marie; Butler, David

    2009-03-01

    People in persistent pain have been reported to pay increased attention to specific words or descriptors of pain. The amount of attention paid to pain or cues for pain (such as pain descriptors), has been shown to be a major factor in the modulation of persistent pain. This relationship suggests the possibility that language may have a role both in understanding and managing the persistent pain experience. The aim of this paper is to describe current models of neuromatrices for pain and language, consider the role of attention in persistent pain states and highlight discrepancies, in previous studies based on the McGill Pain Questionnaire (MPQ), of the role of attention on pain descriptors. The existence of a pain neuromatrix originally proposed by Melzack (1990) has been supported by emerging technologies. Similar technologies have recently allowed identification of multiple areas of involvement for the processing of auditory input and the construction of language. As with the construction of pain, this neuromatrix for speech and language may intersect with neural systems for broader cognitive functions such as attention, memory and emotion. A systematic search was undertaken to identify experimental or review studies, which specifically investigated the role of attention on pain descriptors (as cues for pain) in persistent pain patients. A total of 99 articles were retrieved from six databases, with 66 articles meeting the inclusion criteria. After duplicated articles were eliminated, the remaining 41 articles were reviewed in order to support a link between persistent pain, pain descriptors and attention. This review revealed a diverse range of specific pain descriptors, the majority of which were derived from the MPQ. Increased attention to pain descriptors was consistently reported to be associated with emotional state as well as being a significant factor in maintaining persistent pain. However, attempts to investigate the attentional bias of specific pain

  18. Nursing care of patients during the dying process: a painful professional and human function

    Directory of Open Access Journals (Sweden)

    Martha Adiela Lopera Betancur

    2015-08-01

    Full Text Available Objective. This work sought to describe the care functions of nurses with patients during the dying process. Methodology. This was a qualitative study with ethnographic approach stemming from the analysis of the culture of nurses; it was conducted in the city of Medellín, Colombia. Theoretical saturation was obtained with 23 interviews. Results. Nurses feel the duty to care for patients throughout the vital cycle through functions defined as: serving, helping, accompanying, offering support, advocating, educating, and representing, which they identify as indispensable. They also perceive as their own the social responsibility for some issues related to death and due to this they get involved at the personal level, appropriate care and are affected as persons. Conclusion. Patient care during dying processes transcends the limits of the nurse' professional functions to become a human obligation.

  19. Nursing care of patients during the dying process: a painful professional and human function.

    Science.gov (United States)

    Lopera Betancur, Martha Adiela

    2015-01-01

    This work sought to describe the care functions of nurses with patients during the dying process. This was a qualitative study with ethnographic approach stemming from the analysis of the culture of nurses; it was conducted in the city of Medellín, Colombia. Theoretical saturation was obtained with 23 interviews. Nurses feel the duty to care for patients throughout the vital cycle through functions defined as: serving, helping, accompanying, offering support, advocating, educating, and representing, which they identify as indispensable. They also perceive as their own the social responsibility for some issues related to death and due to this they get involved at the personal level, appropriate care and are affected as persons. Patient care during dying processes transcends the limits of the nurse' professional functions to become a human obligation.

  20. Using experimental game theory to transit human values to ethical AI

    OpenAIRE

    Wang, Yijia; Wan, Yan; Wang, Zhijian

    2017-01-01

    Knowing the reflection of game theory and ethics, we develop a mathematical representation to bridge the gap between the concepts in moral philosophy (e.g., Kantian and Utilitarian) and AI ethics industry technology standard (e.g., IEEE P7000 standard series for Ethical AI). As an application, we demonstrate how human value can be obtained from the experimental game theory (e.g., trust game experiment) so as to build an ethical AI. Moreover, an approach to test the ethics (rightness or wrongn...

  1. Hypoxia and oxidation levels of DNA and lipids in humans and animal experimental models

    DEFF Research Database (Denmark)

    Møller, Peter; Risom, Lotte; Lundby, Carsten

    2008-01-01

    The objective of this review was to evaluate the association between hypoxia and oxidative damage to DNA and lipids. Evaluation criteria encompassed specificity and validation status of the biomarkers, study design, strength of the association, dose-response relationship, biological plausibility......, analogous exposures, and effect modification by intervention. The collective interpretation indicates persuasive evidence from the studies in humans for an association between hypoxia and elevated levels of oxidative damage to DNA and lipids. The levels of oxidatively generated DNA lesions and lipid...... in subjects at high altitude. Most of the animal experimental models should be interpreted with caution because the assays for assessment of lipid peroxidation products have suboptimal validity....

  2. Experimental study and constitutive modeling of the viscoelastic mechanical properties of the human prolapsed vaginal tissue.

    Science.gov (United States)

    Peña, Estefania; Calvo, B; Martínez, M A; Martins, P; Mascarenhas, T; Jorge, R M N; Ferreira, A; Doblaré, M

    2010-02-01

    In this paper, the viscoelastic mechanical properties of vaginal tissue are investigated. Using previous results of the authors on the mechanical properties of biological soft tissues and newly experimental data from uniaxial tension tests, a new model for the viscoelastic mechanical properties of the human vaginal tissue is proposed. The structural model seems to be sufficiently accurate to guarantee its application to prediction of reliable stress distributions, and is suitable for finite element computations. The obtained results may be helpful in the design of surgical procedures with autologous tissue or prostheses.

  3. Experimental cancer cachexia: Evolving strategies for getting closer to the human scenario.

    Science.gov (United States)

    Penna, Fabio; Busquets, Sílvia; Argilés, Josep M

    2016-06-01

    Cancer cachexia is a frequent syndrome that dramatically affects patient quality of life, anti-cancer treatment effectiveness, and overall survival. To date, no effective treatment is available and most of the studies are performed in experimental models in order to uncover the underlying mechanisms and to design prospective therapeutic strategies. This review summarizes the most relevant information regarding the use of animal models for studying cancer cachexia. Technical limitations and degree of recapitulation of the features of human cachexia are highlighted, in order to help investigators choose the most suitable model according to study-specific endpoints. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Experimental Models of Vaginal Candidiasis and Their Relevance to Human Candidiasis

    Science.gov (United States)

    Sobel, Jack D.

    2016-01-01

    Vulvovaginal candidiasis (VVC) is a high-incidence disease seriously affecting the quality of life of women worldwide, particularly in its chronic, recurrent forms (RVVC), and with no definitive cure or preventive measure. Experimental studies in currently used rat and mouse models of vaginal candidiasis have generated a large mass of data on pathogenicity determinants and inflammation and immune responses of potential importance for the control of human pathology. However, reflection is necessary about the relevance of these rodent models to RVVC. Here we examine the chemical, biochemical, and biological factors that determine or contrast the forms of the disease in rodent models and in women and highlight the differences between them. We also appeal for approaches to improve or replace the current models in order to enhance their relevance to human infection. PMID:26883592

  5. Experimental evaluation of a system for human life detection under debris

    Science.gov (United States)

    Joju, Reshma; Konica, Pimplapure Ramya T.; Alex, Zachariah C.

    2017-11-01

    It is difficult to for the human beings to be found under debris or behind the walls in case of military applications. Due to which several rescue techniques such as robotic systems, optical devices, and acoustic devices were used. But if victim was unconscious then these rescue system failed. We conducted an experimental analysis on whether the microwaves could detect heart beat and breathing signals of human beings trapped under collapsed debris. For our analysis we used RADAR based on by Doppler shift effect. We calculated the minimum speed that the RADAR could detect. We checked the frequency variation by placing the RADAR at a fixed position and placing the object in motion at different distances. We checked the frequency variation by using objects of different materials as debris behind which the motion was made. The graphs of different analysis were plotted.

  6. Initial investigation of the effects of an experimentally learned schema on spatial associative memory in humans.

    Science.gov (United States)

    van Buuren, Mariët; Kroes, Marijn C W; Wagner, Isabella C; Genzel, Lisa; Morris, Richard G M; Fernández, Guillén

    2014-12-10

    Networks of interconnected neocortical representations of prior knowledge, "schemas," facilitate memory for congruent information. This facilitation is thought to be mediated by augmented encoding and accelerated consolidation. However, it is less clear how schema affects retrieval. Rodent and human studies to date suggest that schema-related memories are differently retrieved. However, these studies differ substantially as most human studies implement pre-experimental world-knowledge as schemas and tested item or nonspatial associative memory, whereas animal studies have used intraexperimental schemas based on item-location associations within a complex spatial layout that, in humans, could engage more strategic retrieval processes. Here, we developed a paradigm conceptually linked to rodent studies to examine the effects of an experimentally learned spatial associative schema on learning and retrieval of new object-location associations and to investigate the neural mechanisms underlying schema-related retrieval. Extending previous findings, we show that retrieval of schema-defining associations is related to activity along anterior and posterior midline structures and angular gyrus. The existence of such spatial associative schema resulted in more accurate learning and retrieval of new, related associations, and increased time allocated to retrieve these associations. This retrieval was associated with right dorsolateral prefrontal and lateral parietal activity, as well as interactions between the right dorsolateral prefrontal cortex and medial and lateral parietal regions, and between the medial prefrontal cortex and posterior midline regions, supporting the hypothesis that retrieval of new, schema-related object-location associations in humans also involves augmented monitoring and systematic search processes. Copyright © 2014 the authors 0270-6474/14/3416662-09$15.00/0.

  7. Nutraceuticals and osteoarthritis pain.

    Science.gov (United States)

    Wang, Angela; Leong, Daniel J; Cardoso, Luis; Sun, Hui B

    2018-02-24

    Arthritis is a chronic disease of joints. It is highly prevalent, particularly in the elderly, and is commonly associated with pain that interferes with quality of life. Because of its chronic nature, pharmacological approaches to pain relief and joint repair must be safe for long term use, a quality many current therapies lack. Nutraceuticals refer to compounds or materials that can function as nutrition and exert a potential therapeutic effect, including the relief of pain, such as pain related to arthritis, of which osteoarthritis (OA) is the most common form. Of interest, nutraceuticals have recently been shown to have potential in relieving OA pain in human clinical trials. Emerging evidence indicates nutraceuticals may represent promising alternatives for the relief of OA pain. In this paper, we will overview OA pain and the use of nutraceuticals in OA pain management, focusing on those that have been evaluated by clinical trials. Furthermore, we discuss the biologic and pharmacologic actions underlying the nutraceutical effects on pain relief based on the potential active ingredients identified from traditional nutraceuticals in OA pain management and their potential for drug development. The review concludes by sharing our viewpoints that future studies should prioritize elucidating the mechanisms of action of nutraceuticals in OA and developing nutraceuticals that not only relieve OA pain, but also mitigate OA pathology. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. A basic experimental study on mental workload for human cognitive work at man-machine interface

    International Nuclear Information System (INIS)

    Yoshikawa, Hidekazu; Shimoda, Hiroshi; Wakamori, Osamu; Nagai, Yoshinori

    1995-01-01

    The nature and measurement methods of mental workload (MWL) for human cognitive activity at man-machine interface (MMI) were firstly discussed from the viewpoint of human information process model. Then, a model VDT experiment which simplifies the actual human-computer-interaction situation at MMI, was conducted for several subjects, where two subjects participated in experiment series and tried to solve the same cognitive task in competition. Adopted experimental parameters were (i)different kinds of cognitive task, and (ii)cycle time of information display, to see the influence on MWL characteristics from psycho-physiological viewpoint. A special processing unit for eye camera was developed and used for measuring subjects' eye movement characteristics. Concerning data analysis, total number of display presentation until problem solving (ie., total information needed for problem solving) was assumed as anchoring objective measure for MWL, and the investigations were conducted from two aspects; (i)global interpretation on MWL characteristics seen in the subjects' behavior from viewpoint of human information process model, and (ii)applicability of MWL by means of biocybernetic method. As regards to applicability of biocybernetic method, the nature of MWL characteristics was first divided into two aspects : (i)efficiency of visual information acquisition, and (ii)difficulty of inner cognitive process to solve problem, both in time pressure situation. Then, the data analysis results for eye movement characteristics were correlated to (i), while for heart rate characteristics, (ii). (author)

  9. Experimental vitrification of human compacted morulae and early blastocysts using fine diameter plastic micropipettes.

    Science.gov (United States)

    Cremades, N; Sousa, M; Silva, J; Viana, P; Sousa, S; Oliveira, C; Teixeira da Silva, J; Barros, A

    2004-02-01

    Vitrification of human blastocysts has been successfully applied using grids, straws and cryoloops. We assessed the survival rate of human compacted morulae and early blastocysts vitrified in pipette tips with a smaller inner diameter and solution volume than the previously described open pulled straw (OPS) method. Excess day 5 human embryos (n = 63) were experimentally vitrified in vessels. Embryos were incubated at 37 degrees C with sperm preparation medium (SPM) for 1 min, SPM + 7.5% ethylene glycol (EG)/dimethylsulphoxide (DMSO) for 3 min, and SPM + 16.5% EG + 16.5% DMSO + 0.67 mol/l sucrose for 25 s. They were then aspirated (0.5 microl) into a plastic micropipette tip (0.36 mm inner diameter), exposed to liquid nitrogen (LN(2)) vapour for 2 min before being placed into a pre-cooled cryotube, which was then closed and plunged into LN(2). Embryos were warmed and diluted using 0.33 mol/l and 0.2 mol/l sucrose. The survival rate for compacted morulae was 73% (22/30) and 82% (27/33) for early blastocysts. The survival rates of human compacted morulae and early blastocysts after vitrification with this simple technique are similar to those reported in the literature achieved by slow cooling and other vitrification protocols.

  10. Study of Statin- and Loratadine-Induced Muscle Pain Mechanisms Using Human Skeletal Muscle Cells

    Directory of Open Access Journals (Sweden)

    Yat Hei Leung

    2017-10-01

    Full Text Available Many drugs can cause unexpected muscle disorders, often necessitating the cessation of an effective medication. Inhibition of monocarboxylate transporters (MCTs may potentially lead to perturbation of l-lactic acid homeostasis and muscular toxicity. Previous studies have shown that statins and loratadine have the potential to inhibit l-lactic acid efflux by MCTs (MCT1 and 4. The main objective of this study was to confirm the inhibitory potentials of atorvastatin, simvastatin (acid and lactone forms, rosuvastatin, and loratadine on l-lactic acid transport using primary human skeletal muscle cells (SkMC. Loratadine (IC50 31 and 15 µM and atorvastatin (IC50 ~130 and 210 µM demonstrated the greatest potency for inhibition of l-lactic acid efflux at pH 7.0 and 7.4, respectively (~2.5-fold l-lactic acid intracellular accumulation. Simvastatin acid exhibited weak inhibitory potency on l-lactic acid efflux with an intracellular lactic acid increase of 25–35%. No l-lactic acid efflux inhibition was observed for simvastatin lactone or rosuvastatin. Pretreatment studies showed no change in inhibitory potential and did not affect lactic acid transport for all tested drugs. In conclusion, we have demonstrated that loratadine and atorvastatin can inhibit the efflux transport of l-lactic acid in SkMC. Inhibition of l-lactic acid efflux may cause an accumulation of intracellular l-lactic acid leading to the reported drug-induced myotoxicity.

  11. Tomato Lycopene and Lung Cancer Prevention: From Experimental to Human Studies

    International Nuclear Information System (INIS)

    Palozza, Paola; Simone, Rossella E.; Catalano, Assunta; Mele, Maria Cristina

    2011-01-01

    Increasing evidence suggests that tomato lycopene may be preventive against the formation and the development of lung cancer. Experimental studies demonstrated that lycopene may inhibit the growth of several cultured lung cancer cells and prevent lung tumorigenesis in animal models through various mechanisms, including a modulation of redox status, cell cycle arrest and/or apoptosis induction, a regulation of growth factor signaling, changes in cell growth-related enzymes, an enhancement of gap junction communication and a prevention of smoke-induced inflammation. In addition, lycopene also inhibited cell invasion, angiogenesis, and metastasis. Several lycopene metabolites have been identified, raising the question as to whether the preventive effects of lycopene on cancer risk is, at least in part, due to its metabolites. Despite these promising reports, it is difficult at the moment to directly relate available experimental data to human pathophysiology. More well controlled clinical intervention trials are needed to further clarify the exact role of lycopene in the prevention of lung cancer cell growth. Such studies should take into consideration subject selection, specific markers of analysis, the levels of carotenoids being tested, metabolism and isomerization of lycopene, interaction with other bioactive food components. This article reviews data on the cancer preventive activities of lycopene, possible mechanisms involved, and the relationship between lycopene consumption and human cancer risk

  12. Tomato Lycopene and Lung Cancer Prevention: From Experimental to Human Studies

    Energy Technology Data Exchange (ETDEWEB)

    Palozza, Paola, E-mail: p.palozza@rm.unicatt.it; Simone, Rossella E.; Catalano, Assunta [Institute of General Pathology, School of Medicine, Catholic University, L. Go F. Vito, Rome 1 00168 (Italy); Mele, Maria Cristina [Institute of Biochemistry and Clinical Biochemistry, School of Medicine, Catholic University, L. Go F. Vito, Rome 1 00168 (Italy)

    2011-05-11

    Increasing evidence suggests that tomato lycopene may be preventive against the formation and the development of lung cancer. Experimental studies demonstrated that lycopene may inhibit the growth of several cultured lung cancer cells and prevent lung tumorigenesis in animal models through various mechanisms, including a modulation of redox status, cell cycle arrest and/or apoptosis induction, a regulation of growth factor signaling, changes in cell growth-related enzymes, an enhancement of gap junction communication and a prevention of smoke-induced inflammation. In addition, lycopene also inhibited cell invasion, angiogenesis, and metastasis. Several lycopene metabolites have been identified, raising the question as to whether the preventive effects of lycopene on cancer risk is, at least in part, due to its metabolites. Despite these promising reports, it is difficult at the moment to directly relate available experimental data to human pathophysiology. More well controlled clinical intervention trials are needed to further clarify the exact role of lycopene in the prevention of lung cancer cell growth. Such studies should take into consideration subject selection, specific markers of analysis, the levels of carotenoids being tested, metabolism and isomerization of lycopene, interaction with other bioactive food components. This article reviews data on the cancer preventive activities of lycopene, possible mechanisms involved, and the relationship between lycopene consumption and human cancer risk.

  13. Characterising the mucosal and systemic immune responses to experimental human hookworm infection.

    Directory of Open Access Journals (Sweden)

    Soraya Gaze

    2012-02-01

    Full Text Available The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and mucosal cytokine responses to hookworm infection in experimentally infected, previously hookworm naive individuals from non-endemic areas. We collected both peripheral blood and duodenal biopsies to assess the systemic immune response, as well as the response at the site of adult worm establishment. Our results show that experimental hookworm infection leads to a strong systemic and mucosal Th2 (IL-4, IL-5, IL-9 and IL-13 and regulatory (IL-10 and TGF-β response, with some evidence of a Th1 (IFN-γ and IL-2 response. Despite upregulation after patency of both IL-15 and ALDH1A2, a known Th17-inducing combination in inflammatory diseases, we saw no evidence of a Th17 (IL-17 response. Moreover, we observed strong suppression of mucosal IL-23 and upregulation of IL-22 during established hookworm infection, suggesting a potential mechanism by which Th17 responses are suppressed, and highlighting the potential that hookworms and their secreted proteins offer as therapeutics for human inflammatory diseases.

  14. The bystander effect in experimental systems and compatibility with radon-induced lung cancer in humans

    International Nuclear Information System (INIS)

    Little, M.P.; Wakeford, R.

    2002-01-01

    Bystander effects following exposure to α-particles have been observed in C3H 10T 1/2 cells and in other experimental systems, and imply that linearly extrapolating low-dose risks from high-dose data might materially underestimate risk. The ratio of lung cancer risk among persons exposed to low and high doses of radon daughters is 2.4-4.0, with an upper 95% confidence limit (CL) of about 14. Assuming that the bystander effect observed in the C3H 10T 1/2 data applies to human lung cells in vivo, the epidemiological data imply that the number of neighbouring cells that can contribute to the bystander effect is between 0 and 1, with an upper 95% CL of about 7. As a consequence, the bystander effect observed in the C3H 10T 1/2 system probably does not play a large part in the process of radon-induced lung carcinogenesis in humans. Other experimental data relating to the bystander effect after α-particle exposure are surveyed; some of these data are more compatible with the epidemiological data. (author)

  15. Tomato Lycopene and Lung Cancer Prevention: From Experimental to Human Studies

    Directory of Open Access Journals (Sweden)

    Assunta Catalano

    2011-05-01

    Full Text Available Increasing evidence suggests that tomato lycopene may be preventive against the formation and the development of lung cancer. Experimental studies demonstrated that lycopene may inhibit the growth of several cultured lung cancer cells and prevent lung tumorigenesis in animal models through various mechanisms, including a modulation of redox status, cell cycle arrest and/or apoptosis induction, a regulation of growth factor signaling, changes in cell growth-related enzymes, an enhancement of gap junction communication and a prevention of smoke-induced inflammation. In addition, lycopene also inhibited cell invasion, angiogenesis, and metastasis. Several lycopene metabolites have been identified, raising the question as to whether the preventive effects of lycopene on cancer risk is, at least in part, due to its metabolites. Despite these promising reports, it is difficult at the moment to directly relate available experimental data to human pathophysiology. More well controlled clinical intervention trials are needed to further clarify the exact role of lycopene in the prevention of lung cancer cell growth. Such studies should take into consideration subject selection, specific markers of analysis, the levels of carotenoids being tested, metabolism and isomerization of lycopene, interaction with other bioactive food components. This article reviews data on the cancer preventive activities of lycopene, possible mechanisms involved, and the relationship between lycopene consumption and human cancer risk.

  16. Pain adaptability in individuals with chronic musculoskeletal pain is not associated with conditioned pain modulation

    DEFF Research Database (Denmark)

    Wan, Dawn Wong Lit; Arendt-Nielsen, Lars; Wang, Kelun

    2018-01-01

    (MSK). CPTs at 2°C and 7°C were used to assess the status of pain adaptability in participants with either chronic non-specific low back pain or knee osteoarthritis. The participants' potency of conditioned pain modulation (CPM) and local inhibition were measured. The strengths of pain adaptability...... at both CPTs were highly correlated. PA and PNA did not differ in their demographics, pain thresholds from thermal and pressure stimuli, or potency of local inhibition or CPM. PA reached their maximum pain faster than PNA (t41=-2.76, p... days whereas PNA did not (F (6,246) = 3.01, p = 0.01). The dichotomy of pain adaptability exists in MSK patients. Consistent with the healthy human study, the strength of pain adaptability and potency of CPM are not related. Pain adaptability could be another form of endogenous pain inhibition which...

  17. Postoperative pain

    DEFF Research Database (Denmark)

    Kehlet, H; Dahl, J B

    1993-01-01

    also modify various aspects of the surgical stress response, and nociceptive blockade by regional anesthetic techniques has been demonstrated to improve various parameters of postoperative outcome. It is therefore stressed that effective control of postoperative pain, combined with a high degree......Treatment of postoperative pain has not received sufficient attention by the surgical profession. Recent developments concerned with acute pain physiology and improved techniques for postoperative pain relief should result in more satisfactory treatment of postoperative pain. Such pain relief may...

  18. Neonatal Pain in Very Preterm Infants: Long-Term Effects on Brain, Neurodevelopment and Pain Reactivity

    Directory of Open Access Journals (Sweden)

    Ruth Eckstein Grunau

    2013-10-01

    Full Text Available Effects of early life psychosocial adversity have received a great deal of attention, such as maternal separation in experimental animal models and abuse/neglect in young humans. More recently, long-term effects of the physical stress of repetitive procedural pain have begun to be addressed in infants hospitalized in neonatal intensive care. Preterm infants are more sensitive to pain and stress, which cannot be distinguished in neonates. The focus of this review is clinical studies of long-term effects of repeated procedural pain-related stress in the neonatal intensive care unit (NICU in relation to brain development, neurodevelopment, programming of stress systems, and later pain sensitivity in infants born very preterm (24–32 weeks’ gestational age. Neonatal pain exposure has been quantified as the number of invasive and/or skin-breaking procedures during hospitalization in the NICU. Emerging studies provide convincing clinical evidence for an adverse impact of neonatal pain/stress in infants at a time of physiological immaturity, rapidly developing brain microstructure and networks, as well as programming of the hypothalamic-pituitary-adrenal axis. Currently it appears that early pain/stress may influence the developing brain and thereby neurodevelopment and stress-sensitive behaviors, particularly in the most immature neonates. However, there is no evidence for greater prevalence of pain syndromes compared to children and adults born healthy at full term. In addressing associations between pain/stress and outcomes, careful consideration of confounding clinical factors related to prematurity is essential. The need for pain management for humanitarian care is widely advocated. Non-pharmacological interventions to help parents reduce their infant’s stress may be brain-protective.

  19. Postamputation pain: studies on mechanisms.

    Science.gov (United States)

    Nikolajsen, Lone

    2012-10-01

    Amputation is followed by both painful and non-painful phantom phenomena in a large number of amputees. Non-painful phantom sensations rarely pose any clinical problem, but 60-80% of all amputees also experience painful sensations (i.e. phantom pain) located to the missing limb. The severity of phantom pain usually decreases with time, but severe pain persists in 5-10% of patients. Pain in the residual limb (i.e. stump pain) is another consequence of amputation. Both stump and phantom pain can be very difficult to treat. Treatment guidelines used for other neuropathic pain conditions are probably the best approximation, especially for the treatment of stump pain. The aim of the present doctoral thesis was to explore some of the mechanisms underlying pain after amputation. Ten studies were carried out (I-X). My PhD thesis from 1998 dealt with pain before the amputation and showed that preamputation pain increases the risk of phantom pain after amputation (I). A perioperative epidural blockade, however, did not reduce the incidence of pain or abnormal sensory phenomena after amputation (II, III). The importance of sensitization before amputation for the subsequent development of pain is supported by study IV, in which pressure pain thresholds obtained at the limb before amputation were inversely related to stump and phantom pain after 1 week. Afferent input from the periphery is likely to contribute to postamputation pain as sodium channels were upregulated in human neuromas (VI), although neuroma removal did not always alleviate phantom pain (V). Sensitization of neurons in the spinal cord also seems to be involved in pain after amputation as phantom pain was reduced by ketamine, an NMDA-receptor antagonist. Another NMDA-receptor antagonist, memantine, and gabapentin, a drug working by binding to the δ2α-subunit of voltage-gated calcium channels, had no effect on phantom pain (VII-IX). Supraspinal factors are also important for pain after amputation as

  20. Are PrP(C)s involved in some human myelin diseases? Relating experimental studies to human pathology.

    Science.gov (United States)

    Veber, Daniela; Scalabrino, Giuseppe

    2015-12-15

    We have experimentally demonstrated that cobalamin (Cbl) deficiency increases normal cellular prion (PrP(C)) levels in rat spinal cord (SC) and cerebrospinal fluid (CSF), and decreases PrP(C)-mRNA levels in rat SC. Repeated intracerebroventricular administrations of anti-octapeptide repeat-PrP(C)-region antibodies to Cbl-deficient (Cbl-D) rats prevent SC myelin lesions, and the administrations of PrP(C)s to otherwise normal rats cause SC white matter lesions similar to those induced by Cbl deficiency. Cbl positively regulates SC PrP(C) synthesis in rat by stimulating the local synthesis of epidermal growth factor (EGF), which also induces the local synthesis of PrP(C)-mRNAs, and downregulating the local synthesis of tumor necrosis factor(TNF)-α, thus preventing local PrP(C) overproduction. We have clinically demonstrated that PrP(C) levels are increased in the CSF of patients with subacute combined degeneration (SCD), unchanged in the CSF of patients with Alzheimer's disease and amyotrophic lateral sclerosis, and decreased in the CSF and SC of patients with multiple sclerosis (MS), regardless of its clinical course. We conclude that SCD (human and experimental) is a neurological disease due to excess PrP(C) without conformational change and aggregation, that the increase in PrP(C) levels in SCD and Cbl-D polyneuropathy and their decrease in MS CNS make them antipodian myelin diseases in terms of quantitative PrP(C) abnormalities, and that these abnormalities are related to myelin damage in the former, and impede myelin repair in the latter. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Altering gender role expectations: effects on pain tolerance, pain threshold, and pain ratings.

    Science.gov (United States)

    Robinson, Michael E; Gagnon, Christine M; Riley, Joseph L; Price, Donald D

    2003-06-01

    The literature demonstrating sex differences in pain is sizable. Most explanations for these differences have focused on biologic mechanisms, and only a few studies have examined social learning. The purpose of this study was to examine the contribution of gender-role stereotypes to sex differences in pain. This study used experimental manipulation of gender-role expectations for men and women. One hundred twenty students participated in the cold pressor task. Before the pain task, participants were given 1 of 3 instructional sets: no expectation, 30-second performance expectation, or a 90-second performance expectation. Pain ratings, threshold, and tolerance were recorded. Significant sex differences in the "no expectation" condition for pain tolerance (t = 2.32, df = 38, P differ in their pain tolerance, pain threshold, or pain ratings. This is the first empirical study to show that manipulation of expectations alters sex differences in laboratory pain.

  2. Toxicology research for precautionary decision-making and the role of Human & Experimental Toxicology

    DEFF Research Database (Denmark)

    Grandjean, P

    2015-01-01

    being the strict criteria for scientific proof usually required for decision-making in regard to prevention. The present study ascertains the coverage of environmental chemicals in four volumes of Human & Experimental Toxicology and the presentation and interpretation of research findings in published...... is particularly prone to bias because of the known paucity of false positives and, in particular, the existence of a vast number of toxic hazards which by default are considered innocuous due to lack of documentation. The Precautionary Principle could inspire decision-making on the basis of incomplete...... articles. Links in SciFinder showed that the 530 articles published in four selected volumes between 1984 and 2014 primarily dealt with metals (126 links) and other toxicants that have received substantial attention in the past. Thirteen compounds identified by US authorities in 2006 as high...

  3. Investigation on human serum albumin and Gum Tragacanth interactions using experimental and computational methods.

    Science.gov (United States)

    Moradi, Sajad; Taran, Mojtaba; Shahlaei, Mohsen

    2018-02-01

    The study on the interaction of human serum albumin and Gum Tragacanth, a biodegradable bio-polymer, has been undertaken. For this purpose, several experimental and computational methods were used. Investigation of thermodynamic parameters and mode of interactions were carried out using Fluorescence spectroscopy in 300 and 310K. Also, a Fourier transformed infrared spectra and synchronous fluorescence spectroscopy was performed. To give detailed insight of possible interactions, docking and molecular dynamic simulations were also applied. Results show that the interaction is based on hydrogen bonding and van der Waals forces. Structural analysis implies on no adverse change in protein conformation during binding of GT. Furthermore, computational methods confirm some evidence on secondary structure enhancement of protein as a presence of combining with Gum Tragacanth. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. A novel therapeutic strategy for experimental stroke using docosahexaenoic acid complexed to human albumin

    Directory of Open Access Journals (Sweden)

    Belayev Ludmila

    2016-01-01

    Full Text Available Despite tremendous efforts in ischemic stroke research and significant improvements in patient care within the last decade, therapy is still insufficient. There is a compelling, urgent need for safe and effective neuroprotective strategies to limit brain injury, facilitate brain repair, and improve functional outcome. Recently, we reported that docosahexaenoic acid (DHA; 22:6, n-3 complexed to human albumin (DHA-Alb is highly neuroprotective after temporary middle cerebral artery occlusion (MCAo in young rats. This review highlights the potency of DHA-Alb therapy in permanent MCAo and aged rats and whether protection persists with chronic survival. We discovered that a novel therapy with DHA-Alb improved behavioral outcomes accompanied by attenuation of lesion volumes even when animals were allowed to survive three weeks after experimental stroke. This treatment might provide the basis for future therapeutics for patients suffering from ischemic stroke.

  5. Healthy volunteers can be phenotyped using cutaneous sensitization pain models

    DEFF Research Database (Denmark)

    Werner, Mads U; Petersen, Karin; Rowbotham, Michael C

    2013-01-01

    Human experimental pain models leading to development of secondary hyperalgesia are used to estimate efficacy of analgesics and antihyperalgesics. The ability to develop an area of secondary hyperalgesia varies substantially between subjects, but little is known about the agreement following repe...... repeated measurements. The aim of this study was to determine if the areas of secondary hyperalgesia were consistently robust to be useful for phenotyping subjects, based on their pattern of sensitization by the heat pain models.......Human experimental pain models leading to development of secondary hyperalgesia are used to estimate efficacy of analgesics and antihyperalgesics. The ability to develop an area of secondary hyperalgesia varies substantially between subjects, but little is known about the agreement following...

  6. Human performance across decision making, selective attention, and working memory tasks: Experimental data and computer simulations

    Directory of Open Access Journals (Sweden)

    Andrea Stocco

    2018-04-01

    Full Text Available This article describes the data analyzed in the paper “Individual differences in the Simon effect are underpinned by differences in the competitive dynamics in the basal ganglia: An experimental verification and a computational model” (Stocco et al., 2017 [1]. The data includes behavioral results from participants performing three cognitive tasks (Probabilistic Stimulus Selection (Frank et al., 2004 [2], Simon task (Craft and Simon, 1970 [3], and Automated Operation Span (Unsworth et al., 2005 [4], as well as simulationed traces generated by a computational neurocognitive model that accounts for individual variations in human performance across the tasks. The experimental data encompasses individual data files (in both preprocessed and native output format as well as group-level summary files. The simulation data includes the entire model code, the results of a full-grid search of the model's parameter space, and the code used to partition the model space and parallelize the simulations. Finally, the repository includes the R scripts used to carry out the statistical analyses reported in the original paper.

  7. Human performance across decision making, selective attention, and working memory tasks: Experimental data and computer simulations.

    Science.gov (United States)

    Stocco, Andrea; Yamasaki, Brianna L; Prat, Chantel S

    2018-04-01

    This article describes the data analyzed in the paper "Individual differences in the Simon effect are underpinned by differences in the competitive dynamics in the basal ganglia: An experimental verification and a computational model" (Stocco et al., 2017) [1]. The data includes behavioral results from participants performing three cognitive tasks (Probabilistic Stimulus Selection (Frank et al., 2004) [2], Simon task (Craft and Simon, 1970) [3], and Automated Operation Span (Unsworth et al., 2005) [4]), as well as simulationed traces generated by a computational neurocognitive model that accounts for individual variations in human performance across the tasks. The experimental data encompasses individual data files (in both preprocessed and native output format) as well as group-level summary files. The simulation data includes the entire model code, the results of a full-grid search of the model's parameter space, and the code used to partition the model space and parallelize the simulations. Finally, the repository includes the R scripts used to carry out the statistical analyses reported in the original paper.

  8. Evaluation of Fentanyl Disposition and Effects in Newborn Piglets as an Experimental Model for Human Neonates

    Science.gov (United States)

    Valls-i-Soler, Adolfo; Encinas, Esther; Lukas, John C.; Vozmediano, Valvanera; Suárez, Elena

    2014-01-01

    Background Fentanyl is widely used off-label in NICU. Our aim was to investigate its cerebral, cardiovascular and pulmonary effects as well as pharmacokinetics in an experimental model for neonates. Methods Fentanyl (5 µg/kg bolus immediately followed by a 90 minute infusion of 3 µg/kg/h) was administered to six mechanically ventilated newborn piglets. Cardiovascular, ventilation, pulmonary and oxygenation indexes as well as brain activity were monitored from T = 0 up to the end of experiments (T = 225–300 min). Also plasma samples for quantification of fentanyl were drawn. Results A “reliable degree of sedation” was observed up to T = 210–240 min, consistent with the selected dosing regimen and the observed fentanyl plasma levels. Unlike cardiovascular parameters, which were unmodified except for an increasing trend in heart rate, some of the ventilation and oxygenation indexes as well as brain activity were significantly altered. The pulmonary and brain effects of fentanyl were mostly recovered from T = 210 min to the end of experiment. Conclusion The newborn piglet was shown to be a suitable experimental model for studying fentanyl disposition as well as respiratory and cardiovascular effects in human neonates. Therefore, it could be extremely useful for further investigating the drug behaviour under pathophysiological conditions. PMID:24595018

  9. Postural And Eye-Positional Effects On Human Biting Force: An Experimental Study

    Directory of Open Access Journals (Sweden)

    Altay Tabancacı

    2012-06-01

    Full Text Available Muscle groups affected on biting force are called temporal muscle as a major and masseter muscle as a minor. According to the human posture stability, forces of these muscles vary with the force directions. In this case, experimental investigation is strictly important such that biting force under different postural and eye- positional situations is changed. In this study, seven-male and seven-female within the age-range of 17-24 are considered corresponding to having with restorated molar tooth and without that type of tooth. With the help of specially designed biting fork, different posture- and eye-positions are investigated for experimental biting force analysis. Changes in eye-positions are not indicated significant difference for all postural positions. On one hand, it is obtained that biting force of no-filling tooth in men becomes maximum if facial muscles give full effort to biting. On the other hand, effect of facial muscles for women is not clearly noticed depending on the postural differences.

  10. Inhibition of the recombinant human endostatin adenavirus on experimental choroidal neovascularization in rats

    Directory of Open Access Journals (Sweden)

    Li-Juan Chen

    2017-06-01

    Full Text Available AIM: To investigate the inhibition of the recombinant human endostatin adenavirus(Ad-Eson the experimental choroidal neovascularization(CNVmodels by intravitreous injection. METHODS: Experimental CNV models were induced by semiconductor laser in 30 male Brown Norway(BNrats and randomly divided into 3 groups with 10 rats in each group. At 21d after photocoagulation, the single administration group were given intravitreous injection with Ad-Es 0.01mL; the repeated administration group were given intravitreous injection with Ad-Es 0.01mL and a repeated injection 7d later; the saline control group were given intravitreous injection with saline 0.01mL. At 7d after final administration, the leakage of fundus fluorescein angiography(FFAwas observed. Various CNV areas were measured by using laser confocal microscopy of choroidal flatmount method. Pathology and ultrastructure were observed with light microscopy, the expressions of CD105 were measured by immunohistochemistry. RESULTS: The leakage of CNV of the administration group abviously decreased as compared with those in the saline group, the leakage of repeated administration group decreased compared with that of single administration group(PPCONCLUSION: Ad-Es can effectively inhibit semiconductor laser induced CNV in BN rats, and the inhibition effect of repeated administration group is better than that of single administration group. It may be a useful new method in the treatment of CNV.

  11. Xenograft transplantation of human malignant astrocytoma cells into immunodeficient rats: an experimental model of glioblastoma.

    Science.gov (United States)

    Miura, Flávio Key; Alves, Maria Jose Ferreira; Rocha, Mussya Cisotto; da Silva, Roseli; Oba-Shinjo, Sueli Mieko; Marie, Suely Kazue Nagahashi

    2010-03-01

    Astrocytic gliomas are the most common intracranial central nervous system neoplasias, accounting for about 60% of all primary central nervous system tumors. Despite advances in the treatment of gliomas, no effective therapeutic approach is yet available; hence, the search for a more realistic model to generate more effective therapies is essential. To develop an experimental malignant astrocytoma model with the characteristics of the human tumor. Primary cells from subcutaneous xenograft tumors produced with malignant astrocytoma U87MG cells were inoculated intracerebrally by stereotaxis into immunosuppressed (athymic) Rowett rats. All four injected animals developed non-infiltrative tumors, although other glioblastoma characteristics, such as necrosis, pseudopalisading cells and intense mitotic activity, were observed. A malignant astrocytoma intracerebral xenograft model with poorly invasive behavior was achieved in athymic Rowett rats. Tumor invasiveness in an experimental animal model may depend on a combination of several factors, including the cell line used to induce tumor formation, the rat strains and the status of the animal's immune system.

  12. Stigmatization of obese individuals by human resource professionals: an experimental study

    Directory of Open Access Journals (Sweden)

    Giel Katrin E

    2012-07-01

    Full Text Available Abstract Background Weight-related stigmatization is a public health problem. It impairs the psychological well-being of obese individuals and hinders them from adopting weight-loss behaviors. We conducted an experimental study to investigate weight stigmatization in work settings using a sample of experienced human resource (HR professionals from a real-life employment setting. Methods In a cross-sectional, computer-based experimental study, a volunteer sample of 127 HR professionals (age: 41.1 ± 10.9 yrs., 56% female, who regularly make career decisions about other people, evaluated individuals shown in standardized photographs regarding work-related prestige and achievements. The photographed individuals differed with respect to gender, ethnicity, and Body Mass Index (BMI. Results Participants underestimated the occupational prestige of obese individuals and overestimated it for normal-weight individuals. Obese people were more often disqualified from being hired and less often nominated for a supervisory position, while non-ethnic normal-weight individuals were favored. Stigmatization was most pronounced in obese females. Conclusions The data suggest that HR professionals are prone to pronounced weight stigmatization, especially in women. This highlights the need for interventions targeting this stigmatization as well as stigma-management strategies for obese individuals. Weight stigmatization and its consequences needs to be a topic that is more strongly addressed in clinical obesity care.

  13. Evaluation of fentanyl disposition and effects in newborn piglets as an experimental model for human neonates.

    Directory of Open Access Journals (Sweden)

    Carmen Rey-Santano

    Full Text Available BACKGROUND: Fentanyl is widely used off-label in NICU. Our aim was to investigate its cerebral, cardiovascular and pulmonary effects as well as pharmacokinetics in an experimental model for neonates. METHODS: Fentanyl (5 µg/kg bolus immediately followed by a 90 minute infusion of 3 µg/kg/h was administered to six mechanically ventilated newborn piglets. Cardiovascular, ventilation, pulmonary and oxygenation indexes as well as brain activity were monitored from T = 0 up to the end of experiments (T = 225-300 min. Also plasma samples for quantification of fentanyl were drawn. RESULTS: A "reliable degree of sedation" was observed up to T = 210-240 min, consistent with the selected dosing regimen and the observed fentanyl plasma levels. Unlike cardiovascular parameters, which were unmodified except for an increasing trend in heart rate, some of the ventilation and oxygenation indexes as well as brain activity were significantly altered. The pulmonary and brain effects of fentanyl were mostly recovered from T = 210 min to the end of experiment. CONCLUSION: The newborn piglet was shown to be a suitable experimental model for studying fentanyl disposition as well as respiratory and cardiovascular effects in human neonates. Therefore, it could be extremely useful for further investigating the drug behaviour under pathophysiological conditions.

  14. VX hydrolysis by human serum paraoxonase 1: a comparison of experimental and computational results.

    Directory of Open Access Journals (Sweden)

    Matthew W Peterson

    Full Text Available Human Serum paraoxonase 1 (HuPON1 is an enzyme that has been shown to hydrolyze a variety of chemicals including the nerve agent VX. While wildtype HuPON1 does not exhibit sufficient activity against VX to be used as an in vivo countermeasure, it has been suggested that increasing HuPON1's organophosphorous hydrolase activity by one or two orders of magnitude would make the enzyme suitable for this purpose. The binding interaction between HuPON1 and VX has recently been modeled, but the mechanism for VX hydrolysis is still unknown. In this study, we created a transition state model for VX hydrolysis (VX(ts in water using quantum mechanical/molecular mechanical simulations, and docked the transition state model to 22 experimentally characterized HuPON1 variants using AutoDock Vina. The HuPON1-VX(ts complexes were grouped by reaction mechanism using a novel clustering procedure. The average Vina interaction energies for different clusters were compared to the experimentally determined activities of HuPON1 variants to determine which computational procedures best predict how well HuPON1 variants will hydrolyze VX. The analysis showed that only conformations which have the attacking hydroxyl group of VX(ts coordinated by the sidechain oxygen of D269 have a significant correlation with experimental results. The results from this study can be used for further characterization of how HuPON1 hydrolyzes VX and design of HuPON1 variants with increased activity against VX.

  15. Effect of Nanofiller Addition to an Experimental Dentin Adhesive on Microtensile Bond Strength to Human Dentin

    Directory of Open Access Journals (Sweden)

    SH. Kasraei

    2009-06-01

    Full Text Available Objective: The purpose of the study was to evaluate the influence of adding nanofiller particles to a dentin bonding agent on resin-dentin bond strength.Materials and Methods: Fifty-four human intact premolar teeth were divided in to 6 groups of nine. The teeth were ground on occlusal surfaces and polished with 320 and then 600 grit silicon carbide papers. An experimental bonding system based on acetone/alcoholsolvent was provided with filler contents of 0.0, 0.5, 1.0, 2.5, 5.0, and 10.0 weight percent fumed silica nanofiller. After dentin surface etching, rinsing and blot drying, the experimentalbonding agents were applied to dentin surface. A composite resin was, then,bonded to the dentin on the bonding agent. The specimens were thermocycled for 500 cycles and sectioned in stick form. After two week of storage in distilled water, resin-dentin microtensile bond strength of the specimens was measured. Data were analyzed by one way ANOVA and DunnettT3 tests.Results: Bond strength to dentin was significantly affected by the filler level. Minimum and maximum resin-microtensile bond strength was in the experimental bonding agent with no filler (5.88 MPa and with filler level of 1.0 weight percent (15.15 MPa, respectively,and decreased with the increase of filler content down to 8.95 MPa for the filler level of 10.0 weight percent.Conclusion: Filler content seems to be one of the important factors influencing the bond strength of dental adhesives. Maximum dentin bond strength was obtained with 1% silanized nanofiller silica added to experimental adhesive system.

  16. Modeling and experimental investigation of an impact-driven piezoelectric energy harvester from human motion

    International Nuclear Information System (INIS)

    Wei, Sheng; Hu, Hong; He, Siyuan

    2013-01-01

    An impact-driven piezoelectric energy harvester from human motion is proposed in this paper. A high-frequency PZT-5A bimorph cantilever beam with attached proof mass at the free end was selected. A frequency up-conversion strategy was realized using impulse force generated by human motion. An aluminum prototype was attached to the leg of a person on a treadmill and measurements taken of the dissipated electric energy across multiple resistances over a range of walking speeds. The outer dimensions of this prototype are 90 mm × 40 mm × 24 mm. It has been shown that the average output voltage generated by the piezoelectric bimorph increases sequentially with a faster walking speed, the power varies with the external resistances and maximum levels occur at the optimal resistance, which is consistent with the simulation result. An open circuit voltage of 2.47 V and maximum average power of 51 μW can be achieved across a 20 kΩ external load resistance and 5 km h −1 walking speed. Experimental results reveal that the impact-driven piezoelectric energy harvesting system mounted on a person’s leg has the potential for driving wearable devices. (paper)

  17. Experimental investigation of radiation effect on human thermal comfort by Taguchi method

    International Nuclear Information System (INIS)

    Arslanoglu, Nurullah; Yigit, Abdulvahap

    2016-01-01

    Highlights: • Radiation heat flux from lighting lamps on human thermal comfort is studied. • The effect of posture position on thermal comfort is investigated. • The effect of clothing color on thermal comfort is examined. • Radiation heat flux from halogen reflector lamp increase skin temperature more. • Posture position effect on thermal comfort is less than the other parameters. - Abstract: In this study, the effect of radiation heat flux of lighting lamps on human thermal comfort was investigated by using Taguchi method. In addition, at indoor conditions, clothing color and posture position under the radiation effect on thermal comfort were also investigated. For this purpose, experiments were performed in an air conditioned laboratory room in summer and autumn seasons. The amount of temperature rise on the back was considered as performance parameter. An L8 orthogonal array was selected as an experimental plan for the third parameters mentioned above for summer and autumn seasons. The results were analyzed for the optimum conditions using signal-to-noise (S/N) ratio and ANOVA method. The optimum results were found to be clear halogen lamp as lighting lamp, white as t-shirt color, standing as posture position, in summer season. The optimum levels of the lighting lamp, t-shirt color and posture position were found to be clear halogen lamp, white, sitting in autumn season, respectively.

  18. Impact of experimental human pneumococcal carriage on nasopharyngeal bacterial densities in healthy adults.

    Science.gov (United States)

    Shak, Joshua R; Cremers, Amelieke J H; Gritzfeld, Jenna F; de Jonge, Marien I; Hermans, Peter W M; Vidal, Jorge E; Klugman, Keith P; Gordon, Stephen B

    2014-01-01

    Colonization of the nasopharynx by Streptococcus pneumoniae is a necessary precursor to pneumococcal diseases that result in morbidity and mortality worldwide. The nasopharynx is also host to other bacterial species, including the common pathogens Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis. To better understand how these bacteria change in relation to pneumococcal colonization, we used species-specific quantitative PCR to examine bacterial densities in 52 subjects 7 days before, and 2, 7, and 14 days after controlled inoculation of healthy human adults with S. pneumoniae serotype 6B. Overall, 33 (63%) of subjects carried S. pneumoniae post-inoculation. The baseline presence and density of S. aureus, H. influenzae, and M. catarrhalis were not statistically associated with likelihood of successful pneumococcal colonization at this study's sample size, although a lower rate of pneumococcal colonization in the presence of S. aureus (7/14) was seen compared to that in the presence of H. influenzae (12/16). Among subjects colonized with pneumococci, the number also carrying either H. influenzae or S. aureus fell during the study and at 14 days post-inoculation, the proportion carrying S. aureus was significantly lower among those who were colonized with S. pneumoniae (p = 0.008) compared to non-colonized subjects. These data on bacterial associations are the first to be reported surrounding experimental human pneumococcal colonization and show that co-colonizing effects are likely subtle rather than absolute.

  19. Impact of experimental human pneumococcal carriage on nasopharyngeal bacterial densities in healthy adults.

    Directory of Open Access Journals (Sweden)

    Joshua R Shak

    Full Text Available Colonization of the nasopharynx by Streptococcus pneumoniae is a necessary precursor to pneumococcal diseases that result in morbidity and mortality worldwide. The nasopharynx is also host to other bacterial species, including the common pathogens Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis. To better understand how these bacteria change in relation to pneumococcal colonization, we used species-specific quantitative PCR to examine bacterial densities in 52 subjects 7 days before, and 2, 7, and 14 days after controlled inoculation of healthy human adults with S. pneumoniae serotype 6B. Overall, 33 (63% of subjects carried S. pneumoniae post-inoculation. The baseline presence and density of S. aureus, H. influenzae, and M. catarrhalis were not statistically associated with likelihood of successful pneumococcal colonization at this study's sample size, although a lower rate of pneumococcal colonization in the presence of S. aureus (7/14 was seen compared to that in the presence of H. influenzae (12/16. Among subjects colonized with pneumococci, the number also carrying either H. influenzae or S. aureus fell during the study and at 14 days post-inoculation, the proportion carrying S. aureus was significantly lower among those who were colonized with S. pneumoniae (p = 0.008 compared to non-colonized subjects. These data on bacterial associations are the first to be reported surrounding experimental human pneumococcal colonization and show that co-colonizing effects are likely subtle rather than absolute.

  20. Computational and experimental research on infrared trace by human being contact

    Energy Technology Data Exchange (ETDEWEB)

    Xiong Zonglong; Yang Kuntao; Ding Wenxiu; Zhang Nanyangsheng; Zheng Wenheng

    2010-06-20

    The indoor detection of the human body's thermal trace plays an important role in the fields of infrared detecting, scouting, infrared camouflage, and infrared rescuing and tracking. Currently, quantitative description and analysis for this technology are lacking due to the absence of human infrared radiation analysis. To solve this problem, we study the heating and cooling process by observing body contact and removal on an object, respectively. Through finite-element simulation and carefully designed experiments, an analytical model of the infrared trace of body contact is developed based on infrared physics and heat transfer theory. Using this model, the impact of body temperature on material thermal parameters is investigated. The sensitivity of material thermal parameters, the thermal distribution, and the changes of the thermograph's contrast are then found and analyzed. Excellent matching results achieved between the simulation and the experiments demonstrate the strong impact of temperature on material thermal parameters. Conclusively, the new model, simulation, and experimental results are beneficial to the future development and implementation of infrared trace technology.

  1. Computational and experimental research on infrared trace by human being contact

    International Nuclear Information System (INIS)

    Xiong Zonglong; Yang Kuntao; Ding Wenxiu; Zhang Nanyangsheng; Zheng Wenheng

    2010-01-01

    The indoor detection of the human body's thermal trace plays an important role in the fields of infrared detecting, scouting, infrared camouflage, and infrared rescuing and tracking. Currently, quantitative description and analysis for this technology are lacking due to the absence of human infrared radiation analysis. To solve this problem, we study the heating and cooling process by observing body contact and removal on an object, respectively. Through finite-element simulation and carefully designed experiments, an analytical model of the infrared trace of body contact is developed based on infrared physics and heat transfer theory. Using this model, the impact of body temperature on material thermal parameters is investigated. The sensitivity of material thermal parameters, the thermal distribution, and the changes of the thermograph's contrast are then found and analyzed. Excellent matching results achieved between the simulation and the experiments demonstrate the strong impact of temperature on material thermal parameters. Conclusively, the new model, simulation, and experimental results are beneficial to the future development and implementation of infrared trace technology.

  2. The difficult relationship between occlusal interferences and temporomandibular disorder - insights from animal and human experimental studies.

    Science.gov (United States)

    Xie, Q; Li, X; Xu, X

    2013-04-01

    The aetiology of temporomandibular disorder (TMD) is multifactorial, and numerous studies have addressed that occlusion may be of great importance. However, whether occlusion plays a crucial role in the pathogenesis of TMD remains controversial. Study designs utilising animal models have been used to study the effects of artificial occlusal alterations. Experimental traumatic occlusion affects blood flow in the temporomandibular joint and results in changes in the condylar cartilage, and artificial occlusal interference induces masticatory muscle nociceptive responses that are associated with peripheral sensitisation and lead to central sensitisation, which maintains masticatory muscle hyperalgesia. The possibility that occlusal interference results in TMD has been investigated in humans using a double-blind randomised design. Subjects without a history of TMD show fairly good adaptation to interferences. In contrast, subjects with a history of TMD develop a significant increase in clinical signs and self-report stronger symptoms (occlusal discomfort and chewing difficulties) in response to interferences. Meanwhile, psychological factors appear meaningful for symptomatic responses to artificial interferences in subjects with a history of TMD. Thus, individual differences in vulnerability to occlusal interferences do exist. Although there are advantages and disadvantages to using human and animal occlusal interference models, these approaches are indispensable for discovering the role of occlusion in TMD pathogenesis. © 2013 Blackwell Publishing Ltd.

  3. Aneurysm pulsatility after endovascular exclusion: an experimental study using human aortic aneurysms

    Directory of Open Access Journals (Sweden)

    Hussein Amin Orra

    2008-01-01

    Full Text Available OBJECTIVE: To measure the pulsatility of human aneurysms before and after complete exclusion with an endograft. METHOD: Five aortic aneurysms obtained during necropsy were submitted to pulsatile perfusion before and after implantation of a bifurcated endograft. The specimens were contained in a closed chamber filled with saline solution. A vertical tube attached to the chamber was used to measure volume dislocation in each systole. Mural thrombus was kept intact, and the space around the device was filled with human blood. After each experiment, the aneurysm was opened to check for the correct positioning and attachment of the device. RESULTS: The level of the saline column oscillated during pulsation in each case, with respective amplitudes of 17, 16, 13, 7, and 25 cm before the endograft insertion. After the insertion, the amplitudes dropped to 13, 12, 9, 3.5, and 23 cm, respectively. The differences were not significant. During the post-experimental examination, all devices were found to be in position and well attached to the neck and iliacs. No endoleak was detected during perfusion or by visual inspection. CONCLUSION: Pulsation of an endograft is transmitted to the aneurysm wall even in the absence of endoleak, and should not be interpreted as procedural failure.

  4. Bisphenol A and Reproductive Health: Update of Experimental and Human Evidence, 2007–2013

    Science.gov (United States)

    Peretz, Jackye; Vrooman, Lisa; Ricke, William A.; Hunt, Patricia A.; Ehrlich, Shelley; Hauser, Russ; Padmanabhan, Vasantha; Taylor, Hugh S.; Swan, Shanna H.; VandeVoort, Catherine A.

    2014-01-01

    health: update of experimental and human evidence, 2007–2013. Environ Health Perspect 122:775–786; http://dx.doi.org/10.1289/ehp.1307728 PMID:24896072

  5. An Experimental Study to Measure the Mechanical Properties of the Human Liver.

    Science.gov (United States)

    Karimi, Alireza; Shojaei, Ahmad

    2018-01-01

    Since the liver is one of the most important organs of the body that can be injured during trauma, that is, during accidents like car crashes, understanding its mechanical properties is of great interest. Experimental data is needed to address the mechanical properties of the liver to be used for a variety of applications, such as the numerical simulations for medical purposes, including the virtual reality simulators, trauma research, diagnosis objectives, as well as injury biomechanics. However, the data on the mechanical properties of the liver capsule is limited to the animal models or confined to the tensile/compressive loading under single direction. Therefore, this study was aimed at experimentally measuring the axial and transversal mechanical properties of the human liver capsule under both the tensile and compressive loadings. To do that, 20 human cadavers were autopsied and their liver capsules were excised and histologically analyzed to extract the mean angle of a large fibers population (bundle of the fine collagen fibers). Thereafter, the samples were cut and subjected to a series of axial and transversal tensile/compressive loadings. The results revealed the tensile elastic modulus of 12.16 ± 1.20 (mean ± SD) and 7.17 ± 0.85 kPa under the axial and transversal loadings respectively. Correspondingly, the compressive elastic modulus of 196.54 ± 13.15 and 112.41 ± 8.98 kPa were observed under the axial and transversal loadings respectively. The compressive axial and transversal maximum/failure stress of the capsule were 32.54 and 37.30 times higher than that of the tensile ones respectively. The capsule showed a stiffer behavior under the compressive load compared to the tensile one. In addition, the axial elastic modulus of the capsule was found to be higher than that of the transversal one. The findings of the current study have implications not only for understanding the mechanical properties of the human capsule tissue under tensile

  6. Synthetic, implantable polymers for local delivery of IUdR to experimental human malignant glioma

    International Nuclear Information System (INIS)

    Williams, Jeffery A.; Yuan Xuan; Dillehay, Larry E.; Shastri, Venkatram R.; Brem, Henry; Williams, Jerry R.

    1998-01-01

    Purpose: Recently, polymeric controlled delivery of chemotherapy has been shown to improve survival of patients with malignant glioma. We evaluated whether we could similarly deliver halogenated pyrimidines to experimental intracranial human malignant glioma. To address this issue we studied the in vitro release from polymers and the in vivo drug delivery of IUdR to experimental human U251 glioblastoma xenografts. Methods and Materials: In vitro: To measure release, increasing (10%, 30%, 50%) proportions of IUdR in synthetic [(poly(bis(p-carboxyphenoxy)-propane) (PCPP):sebacic acid (SA) polymer discs were serially incubated in buffered saline and the supernatant fractions were assayed. In vivo: To compare local versus systemic delivery, mice bearing flank xenografts had intratumoral or contralateral flank IUdR polymer (50% loading) treatments. Mice bearing intracranial (i.c.) xenografts had i.c. versus flank IUdR polymer treatments. Four or 8 days after implantation of polymers, mice were sacrificed and the percentage tumor cells that were labeled with IUdR was measured using quantitative microscopic immunohistochemistry. Results: In vitro: Increasing percentage loadings of IUdR resulted in higher percentages of release: 43.7 + 0.1, 70.0 + 0.2, and 90.2 + 0.2 (p < 0.001 ANOVA) for the 10%, 30%, and 50% loadings, respectively. In vivo: For the flank tumors, both the ipsilateral and contralateral IUdR polymers resulted in similarly high percentages labeling of the tumors versus time. For the ipsilateral IUdR polymers, the percentage of tumor cellular labeling after 4 days versus 8 days was 45.8 ± 7.0 versus 40.6 ± 3.9 (p = NS). For the contralateral polymer implants, the percentage of tumor cellular labeling were 43.9 ± 10.1 versus 35.9 ± 5.2 (p = NS) measured 4 days versus 8 days after implantation. For the i.c. tumors treated with extracranial IUdR polymers, the percentage of tumor cellular labeling was low: 13.9 ± 8.8 and 11.2 ± 5.7 measured 4 and 8 days

  7. Functional MRI brain imaging studies using the Contact Heat Evoked Potential Stimulator (CHEPS in a human volunteer topical capsaicin pain model

    Directory of Open Access Journals (Sweden)

    Shenoy R

    2011-10-01

    Full Text Available Ravikiran Shenoy1, Katherine Roberts1, Anastasia Papadaki2, Donald McRobbie2, Maarten Timmers3, Theo Meert3, Praveen Anand11Peripheral Neuropathy Unit, Hammersmith Hospital, Imperial College London; 2Imaging Sciences Department, Charing Cross Hospital, London, United Kingdom; 3Johnson and Johnson Pharmaceutical Research and Development, Beerse, BelgiumAbstract: Acute application of topical capsaicin produces spontaneous burning and stinging pain similar to that seen in some neuropathic states, with local hyperalgesia. Use of capsaicin applied topically or injected intradermally has been described as a model for neuropathic pain, with patterns of activation in brain regions assessed using functional magnetic resonance imaging (fMRI and positron emission tomography. The Contact Heat Evoked Potential Stimulator (CHEPS is a noninvasive clinically practical method of stimulating cutaneous A-delta nociceptors. In this study, topical capsaicin (1% was applied to the left volar forearm for 15 minutes of twelve adult healthy human volunteers. fMRI scans and a visual analog pain score were recorded during CHEPS stimulation precapsaicin and postcapsaicin application. Following capsaicin application there was a significant increase in visual analog scale (mean ± standard error of the mean; precapsaicin 26.4 ± 5.3; postcapsaicin 48.9 ± 6.0; P < 0.0001. fMRI demonstrated an overall increase in areas of activation, with a significant increase in the contralateral insular signal (mean ± standard error of the mean; precapsaicin 0.434 ± 0.03; postcapsaicin 0.561 ± 0.07; P = 0.047. The authors of this paper recently published a study in which CHEPS-evoked A-delta cerebral potential amplitudes were found to be decreased postcapsaicin application. In patients with neuropathic pain, evoked pain and fMRI brain responses are typically increased, while A-delta evoked potential amplitudes are decreased. The protocol of recording fMRI following CHEPS stimulation

  8. An experimental approach to estimation of human information processing capacity for diagnosis tasks in NPPs

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Tae

    2006-02-15

    The objectives of this research are 1) to determine the human's information processing capacity and 2) to describe the relationship between the information processing capacity and human factors. This research centers on the relationship, as experimentally determined, between an operator's mental workload and information flow during accident diagnosis tasks at nuclear power plants (NPPs). The relationship between the information flow rate and operator's mental workload is investigated experimentally. According to this relationship, the operator's information processing capacity can be established. Once the information processing capacity of a main control room (MCR) operator in a NPP is known, it is possible to apply it 1) to predict the operator's performance, 2) to design diagnosis tasks, and 3) to design human-machine interface. In advanced MCR, an operator's mental activity is more important than his or her physical activity. The mental workload is the portion of the operator's limited capacity that is actually required to perform a particular task. A high mental workload may cause an operator to make a mistake and consequently affect that the safe operation of NPPs. Thus, to predict an operator's performance is very important for the nuclear safety. The information processing capacity is the operator's ability to manage the amount of bits per second when an operator is diagnosing tasks or accidents. We can estimate the information processing capacity using the relationship between the information flow rate and human performance. That is, if the operator's performance decreases rapidly as the information flow rate (bit/sec) is increased, it is possible to determine the operator's information processing capacity. A diagnosis task is one of the most complex and mentally demanding tasks as well as a crucial part in maintaining the safe operation of NPPs. Diagnosis tasks refer to the overall tasks of finding the

  9. An experimental approach to estimation of human information processing capacity for diagnosis tasks in NPPs

    International Nuclear Information System (INIS)

    Kim, Ji Tae

    2006-02-01

    The objectives of this research are 1) to determine the human's information processing capacity and 2) to describe the relationship between the information processing capacity and human factors. This research centers on the relationship, as experimentally determined, between an operator's mental workload and information flow during accident diagnosis tasks at nuclear power plants (NPPs). The relationship between the information flow rate and operator's mental workload is investigated experimentally. According to this relationship, the operator's information processing capacity can be established. Once the information processing capacity of a main control room (MCR) operator in a NPP is known, it is possible to apply it 1) to predict the operator's performance, 2) to design diagnosis tasks, and 3) to design human-machine interface. In advanced MCR, an operator's mental activity is more important than his or her physical activity. The mental workload is the portion of the operator's limited capacity that is actually required to perform a particular task. A high mental workload may cause an operator to make a mistake and consequently affect that the safe operation of NPPs. Thus, to predict an operator's performance is very important for the nuclear safety. The information processing capacity is the operator's ability to manage the amount of bits per second when an operator is diagnosing tasks or accidents. We can estimate the information processing capacity using the relationship between the information flow rate and human performance. That is, if the operator's performance decreases rapidly as the information flow rate (bit/sec) is increased, it is possible to determine the operator's information processing capacity. A diagnosis task is one of the most complex and mentally demanding tasks as well as a crucial part in maintaining the safe operation of NPPs. Diagnosis tasks refer to the overall tasks of finding the root of cause of the faults or accidents. In this

  10. Uso do laser, 670 nm, no quadro álgico de ratos submetidos à modelo experimental de ciatalgia Use of laser, 670 nm, in painful episodes of rats submitted to experimental model of sciatica

    Directory of Open Access Journals (Sweden)

    Núbia Broetto Cunha

    2008-04-01

    Full Text Available A ciatalgia deve-se a compressão do nervo isquiático em algum ponto de seu trajeto, e seu tratamento consiste em solucionar a causa da compressão nervosa, seja por tratamento cirúrgico ou conservador. Alguns recursos fisioterapêuticos atuam basicamente na redução dos sintomas ocasionados por este distúrbio. O objetivo deste estudo foi verificar a eficácia do laser 670 nm, em duas diferentes densidades de energia, na redução do quadro álgico, em ratos submetidos a modelo experimental de ciatalgia. Foram utilizados 18 ratos, divididos em 3 grupos: G1 (n=6 submetidos à ciatalgia e simulado o tratamento (grupo placebo, G2 (n=6 submetido à ciatalgia e tratados com laser 2 J/cm², G3 (n=6 submetidos à ciatalgia e irradiados com laser 4 J/cm². O nervo isquiático do membro posterior direito dos animais foi exposto e compressão com fio catgut em 4 pontos ao redor do nervo foi realizada. No 3° dia pós-operatório, iniciou-se o tratamento com laser na região do procedimento cirúrgico do membro posterior direito durante 10 dias consecutivos. Verificou-se por meio da marcha, o tempo em que o membro permanecia no ar nos períodos: anterior à ciatalgia, pré e pós-tratamento. Os resultados demonstraram que o laser não foi eficaz na redução do quadro álgico, porém com 4 J/cm² houve efeito positivo, sem restabelecimento completo da funcionalidade.Sciatica is caused by the sciatic nerve compression in some point of its course, and its treatment consists of solving the nervous compression cause, either by surgical or conservative treatment. Some physiotherapeutic resources act basically in the reduction of the symptoms caused by this disturbance. The aim of this study was to verify the effectiveness of the laser 670 nm, in two different energy densities, in the pain reduction, in rats submitted to a sciatica experimental model. Eighteen rats, divided in 3 groups were used: G1 (n=6 submitted to sciatica and simulated treatment (placebo

  11. Effects of a home-exercise therapy programme on cervical and lumbar range of motion among nurses with neck and lower back pain: a quasi-experimental study

    OpenAIRE

    Freimann, Tiina; Merisalu, Eda; P??suke, Mati

    2015-01-01

    Background Cervical and lumbar range of motion limitations are usually associated with musculoskeletal pain in the neck and lower back, and are a major health problem among nurses. Physical exercise has been evaluated as an effective intervention method for improving cervical and lumbar range of motion, and for preventing and reducing musculoskeletal pain. The purpose of this study was to investigate the effects of a home-exercise therapy programme on cervical and lumbar range of motion among...

  12. Morphine- and buprenorphine-induced analgesia and antihyperalgesia in a human inflammatory pain model: a double-blind, randomized, placebo-controlled, five-arm crossover study

    Directory of Open Access Journals (Sweden)

    Ravn P

    2013-01-01

    /heat injury relative to placebo for low-dose morphine was 0.01 (interquartile range: −6.2; 9.9, 0.00 (−2.4; 2.1 for high-dose morphine, 0.03 (−1.8; 2.1 for low-dose buprenorphine, and 0.00 (−3.2; 1.1 for high-dose buprenorphine (P > 0.466. There were no significant differences in opioid responses between high and low pain-sensitive subjects (P > 0.286. High-dose buprenorphine, compared to placebo, was associated with a significantly enhanced action of the descending inhibitory pain control system (P = 0.004.Conclusion: The present study, using multimodal testing technique, could not demonstrate any significant differences between morphine and buprenorphine in the profiles of antihyperalgesia and analgesia. Only high-dose buprenorphine was associated with a significant effect on the descending inhibitory pain control system.Keywords: analgesia, antihyperalgesia, experimental pain, opioid, pain sensitivity, randomized trial

  13. Experimental simulation: using generative modelling and palaeoecological data to understand human-environment interactions

    Directory of Open Access Journals (Sweden)

    George Perry

    2016-10-01

    Full Text Available The amount of palaeoecological information available continues to grow rapidly, providing improved descriptions of the dynamics of past ecosystems and enabling them to be seen from new perspectives. At the same time, there has been concern over whether palaeoecological enquiry needs to move beyond descriptive inference to a more hypothesis-focussed or experimental approach; however, the extent to which conventional hypothesis-driven scientific frameworks can be applied to historical contexts (i.e., the past is the subject of ongoing debate. In other disciplines concerned with human-environment interactions, including physical geography and archaeology, there has been growing use of generative simulation models, typified by agent-based approaches. Generative modelling encourages counter-factual questioning (what if…?, a mode of argument that is particularly important in systems and time-periods, such as the Holocene and now the Anthropocene, where the effects of humans and other biophysical processes are deeply intertwined. However, palaeoecologically focused simulation of the dynamics of the ecosystems of the past either seems to be conducted to assess the applicability of some model to the future or treats humans simplistically as external forcing factors. In this review we consider how generative simulation-modelling approaches could contribute to our understanding of past human-environment interactions. We consider two key issues: the need for null models for understanding past dynamics and the need to be able learn more from pattern-based analysis. In this light, we argue that there is considerable scope for palaeocology to benefit from developments in generative models and their evaluation. We discuss the view that simulation is a form of experiment and, by using case studies, consider how the many patterns available to palaeoecologists can support model evaluation in a way that moves beyond simplistic pattern-matching and how such models

  14. Enhanced expression of two discrete isoforms of matrix metalloproteinase-2 in experimental and human diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Sang Soo Kim

    Full Text Available We recently reported on the enhanced expression of two isoforms of matrix metalloproteinase-2 (MMP-2 in human renal transplantation delayed graft function. These consist of the conventional secreted, full length MMP-2 isoform (FL-MMP-2 and a novel intracellular N-Terminal Truncated isoform (NTT-MMP-2 generated by oxidative stress-mediated activation of an alternate promoter in the MMP-2 first intron. Here we evaluated the effect of hyperglycemia and diabetes mellitus on the in vitro and in vivo expression of the two MMP-2 isoforms.We quantified the abundance of the FL-MMP-2 and NTT-MMP-2 transcripts by qPCR in HK2 cells cultured in high glucose or 4-hydroxy-2-hexenal (HHE and tested the effects of the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC. The streptozotocin (STZ murine model of Type I diabetes mellitus and renal biopsies of human diabetic nephropathy were used in this study.Both isoforms of MMP-2 in HK2 cells were upregulated by culture in high glucose or with HHE. PDTC treatment did not suppress high glucose-mediated FL-MMP-2 expression but potently inhibited NTT-MMP-2 expression. With STZ-treated mice, renal cortical expression of both isoforms was increased (FL-MMP-2, 1.8-fold; NTT-MMP-2, greater than 7-fold. Isoform-specific immunohistochemical staining revealed low, but detectable levels of the FL-MMP-2 isoform in controls, while NTT-MMP-2 was not detected. While there was a modest increase in tubular epithelial cell staining for FL-MMP-2 in STZ-treated mice, NTT-MMP-2 was intensely expressed in a basolateral pattern. FL-MMP-2 and NTT-MMP-2 isoform expression as quantified by qPCR were both significantly elevated in renal biopsies of human diabetic nephropathy (12-fold and 3-fold, respectively.The expression of both isoforms of MMP-2 was enhanced in an experimental model of diabetic nephropathy and in human diabetic nephropathy. Selective MMP-2 isoform inhibition could offer a novel approach for the treatment of diabetic renal

  15. Reward and motivation in pain and pain relief

    Science.gov (United States)

    Navratilova, Edita; Porreca, Frank

    2015-01-01

    Pain is fundamentally unpleasant, a feature that protects the organism by promoting motivation and learning. Relief of aversive states, including pain, is rewarding. The aversiveness of pain, as well as the reward from relief of pain, is encoded by brain reward/motivational mesocorticolimbic circuitry. In this Review, we describe current knowledge of the impact of acute and chronic pain on reward/motivation circuits gained from preclinical models and from human neuroimaging. We highlight emerging clinical evidence suggesting that anatomical and functional changes in these circuits contribute to the transition from acute to chronic pain. We propose that assessing activity in these conserved circuits can offer new outcome measures for preclinical evaluation of analgesic efficacy to improve translation and speed drug discovery. We further suggest that targeting reward/motivation circuits may provide a path for normalizing the consequences of chronic pain to the brain, surpassing symptomatic management to promote recovery from chronic pain. PMID:25254980

  16. Pain in Times of Stress

    OpenAIRE

    AHMAD, Asma Hayati; ZAKARIA, Rahimah

    2015-01-01

    Stress modulates pain perception, resulting in either stress-induced analgesia or stress-induced hyperalgesia, as reported in both animal and human studies. The responses to stress include neural, endocrine, and behavioural changes, and built-in coping strategies are in place to address stressors. Peculiar to humans are additional factors that modulate pain that are experienced in times of stress, notably psychological factors that potentially influence the directionality of pain perception.

  17. Effects of train noise and vibration on human heart rate during sleep: an experimental study.

    Science.gov (United States)

    Croy, Ilona; Smith, Michael G; Waye, Kerstin Persson

    2013-05-28

    Transportation of goods on railways is increasing and the majority of the increased numbers of freight trains run during the night. Transportation noise has adverse effects on sleep structure, affects the heart rate (HR) during sleep and may be linked to cardiovascular disease. Freight trains also generate vibration and little is known regarding the impact of vibration on human sleep. A laboratory study was conducted to examine how a realistic nocturnal railway traffic scenario influences HR during sleep. Case-control. Healthy participants. 24 healthy volunteers (11 men, 13 women, 19-28 years) spent six consecutive nights in the sleep laboratory. All participants slept during one habituation night, one control and four experimental nights in which train noise and vibration were reproduced. In the experimental nights, 20 or 36 trains with low-vibration or high-vibration characteristics were presented. Polysomnographical data and ECG were recorded. The train exposure led to a significant change of HR within 1 min of exposure onset (p=0.002), characterised by an initial and a delayed increase of HR. The high-vibration condition provoked an average increase of at least 3 bpm per train in 79% of the participants. Cardiac responses were in general higher in the high-vibration condition than in the low-vibration condition (p=0.006). No significant effect of noise sensitivity and gender was revealed, although there was a tendency for men to exhibit stronger HR acceleration than women. Freight trains provoke HR accelerations during sleep, and the vibration characteristics of the trains are of special importance. In the long term, this may affect cardiovascular functioning of persons living close to railways.

  18. Comparison of lung preservation solutions in human lungs using an ex vivo lung perfusion experimental model

    Directory of Open Access Journals (Sweden)

    Israel L. Medeiros

    2012-09-01

    Full Text Available OBJECTIVE: Experimental studies on lung preservation have always been performed using animal models. We present ex vivo lung perfusion as a new model for the study of lung preservation. Using human lungs instead of animal models may bring the results of experimental studies closer to what could be expected in clinical practice. METHOD: Brain-dead donors whose lungs had been declined by transplantation teams were used. The cases were randomized into two groups. In Group 1, Perfadex®was used for pulmonary preservation, and in Group 2, LPDnac, a solution manufactured in Brazil, was used. An ex vivo lung perfusion system was used, and the lungs were ventilated and perfused after 10 hours of cold ischemia. The extent of ischemic-reperfusion injury was measured using functional and histological parameters. RESULTS: After reperfusion, the mean oxygenation capacity was 405.3 mmHg in Group 1 and 406.0 mmHg in Group 2 (p = 0.98. The mean pulmonary vascular resistance values were 697.6 and 378.3 dyn·s·cm-5, respectively (p =0.035. The mean pulmonary compliance was 46.8 cm H20 in Group 1 and 49.3 ml/cm H20 in Group 2 (p =0.816. The mean wet/dry weight ratios were 2.06 and 2.02, respectively (p=0.87. The mean Lung Injury Scores for the biopsy performed after reperfusion were 4.37 and 4.37 in Groups 1 and 2, respectively (p = 1.0, and the apoptotic cell counts were 118.75/mm² and 137.50/mm², respectively (p=0.71. CONCLUSION: The locally produced preservation solution proved to be as good as Perfadex®. The clinical use of LPDnac may reduce costs in our centers. Therefore, it is important to develop new models to study lung preservation.

  19. Economic efficiency of countries' clinical review processes and competitiveness on the market of human experimentation.

    Science.gov (United States)

    Ippoliti, Roberto

    2013-01-01

    Clinical research is a specific phase of pharmaceutical industry's production process in which companies test candidate drugs on patients to collect clinical evidence about safety and effectiveness. Information is essential to obtain manufacturing authorization from the national drug agency and, in this way, make profits on the market. Considering this activity, however, the public stakeholder has to face a conflict of interests. On the one side, there is society's necessity to make advances in medicine and, of course, to promote pharmaceutical companies' investments in this specific phase (new generation). On the other side, there is the duty to protect patients involved in these experimental treatments (old generation). To abide by this moral duty, a protection system was developed through the years, based on two legal institutions: informed consent and institutional review board. How should an efficient protection system that would take human experimentation into account be shaped? Would it be possible for the national protection system of patients' rights to affect the choice of whether to develop a clinical trial in a given country or not? Looking at Europe and considering a protection system that is shaped around institutional review boards, this article is an empirical work that tries to give answers to these open questions. It shows how a protection system that can minimize the time necessary to start a trial can positively affect pharmaceutical clinical research, that is, the choice of pharmaceutical companies to start innovative medical treatments in a given country. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  20. Sexual pain.

    Science.gov (United States)

    Boardman, Lori A; Stockdale, Colleen K

    2009-12-01

    Sexual pain is an underrecognized and poorly treated constellation of disorders that significantly impact affected women and their partners. Recognized as a form of chronic pain, sexual pain disorders are heterogeneous and include dyspareunia (superficial and deep), vaginismus, vulvodynia, vestibulitis, and noncoital sexual pain disorder. Women too often tolerate pain in the belief that this will meet their partners' needs. This article provides a review of the terminology and definition of the condition, theories on the pathophysiology, diagnostic considerations, and recommendations on the management of female sexual pain.

  1. An experimental investigation of composite floor vibration due to human activities. A case study

    Directory of Open Access Journals (Sweden)

    Yasser G. Mohamed Fahmy

    2012-12-01

    Full Text Available Composite steel floor decks are used in a large variety of constructions with long spans, such as administration and commercial buildings, hotels and bridges. Due to decreased floor mass and longer span lengths, floor vibrations have become an area of concern. Floor decks with low frequencies may be in resonance with the vibrations due to human activities and the resulting acceleration may exceed human comfort levels. The design of slender floor structures, with steel or composite cross sections, is often limited by the serviceability criteria such as deflection limits and vibration behavior, rather than the strength criteria. Control of deflections under AISC specifications requirement is not enough to satisfy the serviceability requirements of the floor systems for vibration. In addition, vibration analysis procedures introduced by AISC design Guide No. 11 are based on regularly-shaped structures and simple boundary conditions. In this paper, a case study for full scale testing of a composite floor system proposed for a tower at Kuwait state that was tested prior to construction. The heel-drop and walking tests are performed on floor systems with and without raised floor respectively. Since heel-drop and walking test results would vary in light of person performance, both tests are carried out three or four times to reduce uncertainty. The fundamental frequencies and damping ratio of the floor system are measured. Comparison of the experimental results with results based on the AISC hand calculations shows that there is no significant difference; therefore the results based on AISC are generally acceptable.

  2. Slow cryopreservation is not superior to vitrification in human spermatozoa; an experimental controlled study

    Directory of Open Access Journals (Sweden)

    Mohamed Shehata Ali Mohamed

    2015-10-01

    Full Text Available Background: Spermatozoa cryopreservation is used for the management of infertility and some other medical conditions. The routinely applied cryopreservation technique depends on permeating cryoprotectants, whose toxic effects have raised the attention towards permeating cryoprotectants-free vitrification technique. Objective: To compare between the application of slow cryopreservation and vitrification on human spermatozoa. Materials and Methods: This was an experimental controlled study involving 33 human semen samples,