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Sample records for underlying pain modulation

  1. Modulation of neural circuits underlying temporal production by facial expressions of pain.

    Directory of Open Access Journals (Sweden)

    Daniela Ballotta

    Full Text Available According to the Scalar Expectancy Theory, humans are equipped with a biological internal clock, possibly modulated by attention and arousal. Both emotions and pain are arousing and can absorb attentional resources, thus causing distortions of temporal perception. The aims of the present single-event fMRI study were to investigate: a whether observation of facial expressions of pain interferes with time production; and b the neural network subserving this kind of temporal distortions. Thirty healthy volunteers took part in the study. Subjects were asked to perform a temporal production task and a concurrent gender discrimination task, while viewing faces of unknown people with either pain-related or neutral expressions. Behavioural data showed temporal underestimation (i.e., longer produced intervals during implicit pain expression processing; this was accompanied by increased activity of right middle temporal gyrus, a region known to be active during the perception of emotional and painful faces. Psycho-Physiological Interaction analyses showed that: 1 the activity of middle temporal gyrus was positively related to that of areas previously reported to play a role in timing: left primary motor cortex, middle cingulate cortex, supplementary motor area, right anterior insula, inferior frontal gyrus, bilateral cerebellum and basal ganglia; 2 the functional connectivity of supplementary motor area with several frontal regions, anterior cingulate cortex and right angular gyrus was correlated to the produced interval during painful expression processing. Our data support the hypothesis that observing emotional expressions distorts subjective time perception through the interaction of the neural network subserving processing of facial expressions with the brain network involved in timing. Within this frame, middle temporal gyrus appears to be the key region of the interplay between the two neural systems.

  2. Modulation of neural circuits underlying temporal production by facial expressions of pain

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    Lui, Fausta; Porro, Carlo Adolfo; Nichelli, Paolo Frigio; Benuzzi, Francesca

    2018-01-01

    According to the Scalar Expectancy Theory, humans are equipped with a biological internal clock, possibly modulated by attention and arousal. Both emotions and pain are arousing and can absorb attentional resources, thus causing distortions of temporal perception. The aims of the present single-event fMRI study were to investigate: a) whether observation of facial expressions of pain interferes with time production; and b) the neural network subserving this kind of temporal distortions. Thirty healthy volunteers took part in the study. Subjects were asked to perform a temporal production task and a concurrent gender discrimination task, while viewing faces of unknown people with either pain-related or neutral expressions. Behavioural data showed temporal underestimation (i.e., longer produced intervals) during implicit pain expression processing; this was accompanied by increased activity of right middle temporal gyrus, a region known to be active during the perception of emotional and painful faces. Psycho-Physiological Interaction analyses showed that: 1) the activity of middle temporal gyrus was positively related to that of areas previously reported to play a role in timing: left primary motor cortex, middle cingulate cortex, supplementary motor area, right anterior insula, inferior frontal gyrus, bilateral cerebellum and basal ganglia; 2) the functional connectivity of supplementary motor area with several frontal regions, anterior cingulate cortex and right angular gyrus was correlated to the produced interval during painful expression processing. Our data support the hypothesis that observing emotional expressions distorts subjective time perception through the interaction of the neural network subserving processing of facial expressions with the brain network involved in timing. Within this frame, middle temporal gyrus appears to be the key region of the interplay between the two neural systems. PMID:29447256

  3. Therapeutic Basis of Clinical Pain Modulation

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    Kirkpatrick, Daniel R.; McEntire, Dan M.; Hambsch, Zakary J.; Kerfeld, Mitchell J.; Smith, Tyler A.; Reisbig, Mark D.; Youngblood, Charles F.

    2015-01-01

    Abstract Pain is a hallmark of almost all bodily ailments and can be modulated by agents, including analgesics and anesthetics that suppress pain signals in the central nervous system. Defects in the modulatory systems, including the endogenous pain‐inhibitory pathways, are a major factor in the initiation and chronicity of pain. Thus, pain modulation is particularly applicable to the practice of medicine. This review summarizes the existing literature on pain modulation. Here, we critically reviewed the literature from PubMed on pain modulation published primarily within the past 5 years in high impact journals. Specifically, we have discussed important anatomical landmarks of pain modulation and outlined the endogenous networks and underlying mechanisms of clinically relevant pain modulatory methods. The Gate Control Theory is briefly presented with discussion on the capacity of pain modulation to cause both hyper‐ and hypoalgesia. An emphasis has been given to highlight key areas in pain research that, because of unanswered questions or therapeutic potential, merit additional scientific scrutiny. The information presented in this paper would be helpful in developing novel therapies, metrics, and interventions for improved patient management. PMID:25962969

  4. Botulinum Toxin Type A—A Modulator of Spinal Neuron–Glia Interactions under Neuropathic Pain Conditions

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    Ewelina Rojewska

    2018-04-01

    Full Text Available Neuropathic pain represents a significant clinical problem because it is a chronic condition often refractory to available therapy. Therefore, there is still a strong need for new analgesics. Botulinum neurotoxin A (BoNT/A is used to treat a variety of clinical diseases associated with pain. Glia are in continuous bi-directional communication with neurons to direct the formation and refinement of synaptic connectivity. This review addresses the effects of BoNT/A on the relationship between glia and neurons under neuropathic pain. The inhibitory action of BoNT/A on synaptic vesicle fusion that blocks the release of miscellaneous pain-related neurotransmitters is known. However, increasing evidence suggests that the analgesic effect of BoNT/A is mediated through neurons and glial cells, especially microglia. In vitro studies provide evidence that BoNT/A exerts its anti-inflammatory effect by diminishing NF-κB, p38 and ERK1/2 phosphorylation in microglia and directly interacts with Toll-like receptor 2 (TLR2. Furthermore, BoNT/A appears to have no more than a slight effect on astroglia. The full activation of TLR2 in astroglia appears to require the presence of functional TLR4 in microglia, emphasizing the significant interaction between those cell types. In this review, we discuss whether and how BoNT/A affects the spinal neuron–glia interaction and reduces the development of neuropathy.

  5. Sex differences and hormonal modulation of deep tissue pain

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    Traub, Richard J.; Ji, Yaping

    2013-01-01

    Women disproportionately suffer from many deep tissue pain conditions. Experimental studies show that women have lower pain thresholds, higher pain ratings and less tolerance to a range of painful stimuli. Most clinical and epidemiological reports suggest female gonadal hormones modulate pain for some, but not all, conditions. Similarly, animal studies support greater nociceptive sensitivity in females in many deep tissue pain models. Gonadal hormones modulate responses in primary afferents, dorsal horn neurons and supraspinal sites, but the direction of modulation is variable. This review will examine sex differences in deep tissue pain in humans and animals focusing on the role of gonadal hormones (mainly estradiol) as an underlying component of the modulation of pain sensitivity. PMID:23872333

  6. Mindfulness Meditation Modulates Pain Through Endogenous Opioids.

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    Sharon, Haggai; Maron-Katz, Adi; Ben Simon, Eti; Flusser, Yuval; Hendler, Talma; Tarrasch, Ricardo; Brill, Silviu

    2016-07-01

    Recent evidence supports the beneficial effects of mindfulness meditation on pain. However, the neural mechanisms underlying this effect remain poorly understood. We used an opioid blocker to examine whether mindfulness meditation-induced analgesia involves endogenous opioids. Fifteen healthy experienced mindfulness meditation practitioners participated in a double-blind, randomized, placebo-controlled, crossover study. Participants rated the pain and unpleasantness of a cold stimulus prior to and after a mindfulness meditation session. Participants were then randomized to receive either intravenous naloxone or saline, after which they meditated again, and rated the same stimulus. A (3) × (2) repeated-measurements analysis of variance revealed a significant time effect for pain and unpleasantness scores (both P mindfulness meditation and after placebo, but not after naloxone. Furthermore, there was a positive correlation between the pain scores following naloxone vs placebo and participants' mindfulness meditation experience. These findings show, for the first time, that meditation involves endogenous opioid pathways, mediating its analgesic effect and growing resilient with increasing practice to external suggestion. This finding could hold promising therapeutic implications and further elucidate the fine mechanisms involved in human pain modulation. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Deficient Pain Modulation in Patients with Chronic Hemiplegic Shoulder Pain.

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    Kashi, Yafit; Ratmansky, Motti; Defrin, Ruth

    2017-11-14

    Hemiplegic shoulder pain (HSP) following stroke significantly affects the individual's function and quality of life. The mechanism of HSP is not clearly understood; hence, it is unclear why HSP resolves spontaneously or following routine care in some patients, while in others it becomes persistent. The aim was therefore to study whether HSP is associated with deficient pain modulation. Thirty post-stroke patients-16 with HSP and 14 without HSP-and 20 matched controls participated. Pain adaptation and conditioned pain modulation (CPM) were measured as indicators of pain modulation, in the affected (hemiplegic) and contralateral shoulder as well as in the affected shin among post-stroke patients, and in comparable body regions among controls. Post-stroke patients also underwent functional and physical evaluation of the shoulder. Pain adaptation was absent among HSP patients, in both the painful shoulder and the affected shin, but existed in the 2 control groups. In addition, the affected shoulder and shin among the HSP group had reduced thermal sensibility compared to the contralateral regions. CPM was similar across groups. Shoulder functional status and physical status were similar for the 2 post-stroke groups. The results suggest that HSP is associated with a lack of pain adaptation, characteristic not only of the painful shoulder but also of the affected side. Although we cannot determine whether lack of pain adaptation precedes the HSP or results from it, interventions that enhance descending pain inhibition may improve management and prevent HSP chronification. © 2017 World Institute of Pain.

  8. Dysfunctional Pain Modulation in Torture Survivors

    DEFF Research Database (Denmark)

    Defrin, Ruth; Lahav, Yael; Solomon, Zahava

    2017-01-01

    to torture, PTSD or PTSD trajectories accounted for chronic pain and altered pain perception. Participants were 59 torture survivors and 44 age-matched healthy control subjects. Chronic pain was characterized. Pain threshold, pain tolerance, conditioned pain modulation (CPM), and temporal summation of pain...... were measured. Three PTSD trajectories were identified among torture survivors; chronic, delayed, and resilient. Lack of CPM and more intense chronic pain was found among the chronic and delayed groups compared with the resilient and healthy control groups. Temporal summation of pain was strongest...... among the chronic group. PTSD trajectories mediated the relationship between torture and CPM. It appears that the duration and severity of posttraumatic distress, rather than the exposure to trauma, are crucial factors that mediate the association between trauma and chronic pain. Because PTSD and its...

  9. Hormones in pain modulation and their clinical implications for pain control: a critical review.

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    Chen, Xueyin; Zhang, Jinyuan; Wang, Xiangrui

    2016-07-01

    Recently, more and more studies have found that pain generation, transmission and modulation are under hormonal regulation. Indeed, hormonal dysregulation is a common component of chronic pain syndromes. Studies have attempted to determine whether the relationship between the pain and its perception and hormones is a causative relationship and how these processes interrelate. This review summarizes and analyzes the current experimental data and provides an overview of the studies addressing these questions. The relationship between pain perception and endocrine effects suggests that hormones can be used as important biomarkers of chronic pain syndromes and/or be developed into therapeutic agents in the fight against pain.

  10. The Perception and Endogenous Modulation of Pain

    Directory of Open Access Journals (Sweden)

    Michael H. Ossipov

    2012-01-01

    Full Text Available Pain is often perceived an unpleasant experience that includes sensory and emotional/motivational responses. Accordingly, pain serves as a powerful teaching signal enabling an organism to avoid injury, and is critical to survival. However, maladaptive pain, such as neuropathic or idiopathic pain, serves no survival function. Genomic studies of individuals with congenital insensitivity to pain or paroxysmal pain syndromes considerable increased our understanding of the function of peripheral nociceptors, and especially of the roles of voltage-gated sodium channels and of nerve growth factor (NGF/TrkA receptors in nociceptive transduction and transmission. Brain imaging studies revealed a “pain matrix,” consisting of cortical and subcortical regions that respond to noxious inputs and can positively or negatively modulate pain through activation of descending pain modulatory systems. Projections from the periaqueductal grey (PAG and the rostroventromedial medulla (RVM to the trigeminal and spinal dorsal horns can inhibit or promote further nociceptive inputs. The “pain matrix” can explain such varied phenomena as stress-induced analgesia, placebo effect and the role of expectation on pain perception. Disruptions in these systems may account for the existence idiopathic pan states such as fibromyalgia. Increased understanding of pain modulatory systems will lead to development of more effective therapeutics for chronic pain.

  11. Love as a Modulator of Pain.

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    Tamam, Sofina; Ahmad, Asma Hayati

    2017-05-01

    Pain is modulated by various factors, the most notable of which is emotions. Since love is an emotion, it can also modulate pain. The answer to the question of whether it enhances or reduces pain needs to be determined. A review was conducted of animal and human studies in which this enigmatic emotion and its interaction with pain was explored. Recent advances in neuroimaging have revealed similarities in brain activation relating to love and pain. At the simplest level, this interaction can be explained by the overlapping network structure in brain functional connectivity, although the explanation is considerably more complex. The effect of love can either result in increased or decreased pain perception. An explanation of the interaction between pain and love relates to the functional connectivity of the brain and to the psychological construct of the individual, as well as to his or her ability to engage resources relating to emotion regulation. In turn, this determines how a person relates to love and reacts to pain.

  12. Attention to pain! A neurocognitive perspective on attentional modulation of pain in neuroimaging studies.

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    Torta, D M; Legrain, V; Mouraux, A; Valentini, E

    2017-04-01

    Several studies have used neuroimaging techniques to investigate brain correlates of the attentional modulation of pain. Although these studies have advanced the knowledge in the field, important confounding factors such as imprecise theoretical definitions of attention, incomplete operationalization of the construct under exam, and limitations of techniques relying on measuring regional changes in cerebral blood flow have hampered the potential relevance of the conclusions. Here, we first provide an overview of the major theories of attention and of attention in the study of pain to bridge theory and experimental results. We conclude that load and motivational/affective theories are particularly relevant to study the attentional modulation of pain and should be carefully integrated in functional neuroimaging studies. Then, we summarize previous findings and discuss the possible neural correlates of the attentional modulation of pain. We discuss whether classical functional neuroimaging techniques are suitable to measure the effect of a fluctuating process like attention, and in which circumstances functional neuroimaging can be reliably used to measure the attentional modulation of pain. Finally, we argue that the analysis of brain networks and spontaneous oscillations may be a crucial future development in the study of attentional modulation of pain, and why the interplay between attention and pain, as examined so far, may rely on neural mechanisms shared with other sensory modalities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. The role of endocannabinoids in pain modulation.

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    Zogopoulos, Panagiotis; Vasileiou, Ioanna; Patsouris, Efstratios; Theocharis, Stamatios E

    2013-02-01

    The endocannabinoid system (ES) is comprised of cannabinoid (CB) receptors, their endogenous ligands (endocannabinoids), and proteins responsible for their metabolism. Endocannabinoids serve as retrograde signaling messengers in GABAergic and glutamatergic synapses, as well as modulators of postsynaptic transmission, that interact with other neurotransmitters. Physiological stimuli and pathological conditions lead to differential increases in brain endocannabinoids that regulate distinct biological functions. Furthermore, endocannabinoids modulate neuronal, glial, and endothelial cell function and exert neuromodulatory, anti-excitotoxic, anti-inflammatory, and vasodilatory effects. Analgesia is one of the principal therapeutic targets of cannabinoids. Cannabinoid analgesia is based on the suppression of spinal and thalamic nociceptive neurons, but peripheral sites of action have also been identified. The chronic pain that occasionally follows peripheral nerve injury differs fundamentally from inflammatory pain and is an area of considerable unmet therapeutic need. Over the last years, considerable progress has been made in understanding the role of the ES in the modulation of pain. Endocannabinoids have been shown to behave as analgesics in models of both acute nociception and clinical pain such as inflammation and painful neuropathy. The framework for such analgesic effects exists in the CB receptors, which are found in areas of the nervous system important for pain processing and in immune cells that regulate the neuro-immune interactions that mediate the inflammatory hyperalgesia. The purpose of this review is to present the available research and clinical data, up to date, regarding the ES and its role in pain modulation, as well as its possible therapeutic perspectives. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.

  14. 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...

  15. Ecological aspects of pain in sensory modulation disorder.

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    Bar-Shalita, T; Deutsch, L; Honigman, L; Weissman-Fogel, I

    2015-01-01

    Sensory Modulation Disorder (SMD) interferes with the daily life participation of otherwise healthy individuals and is characterized by over-, under- or seeking responsiveness to naturally occurring sensory stimuli. Previous laboratory findings indicate pain hyper-sensitivity in SMD individuals suggesting CNS alteration in pain processing and modulation. However, laboratory studies lack ecological validity, and warrant clinical completion in order to elicit a sound understanding of the phenomenon studied. Thus, this study explored the association between sensory modulation and pain in a daily life context in a general population sample. Daily life context of pain and sensations were measured in 250 adults (aged 23-40 years; 49.6% males) using 4 self-report questionnaires: Pain Sensitivity Questionnaire (PSQ) and Pain Catastrophizing Scale (PCS) to evaluate the sensory and cognitive aspects of pain; the Sensory Responsiveness Questionnaire (SRQ) to appraise SMD; and the Short Form - 36 Health Survey, version 2 (SF36) to assess health related Quality of Life (QoL). Thirty two individuals (12.8%) were found with over-responsiveness type of SMD, forming the SOR-SMD group. While no group differences (SOR-SMD vs. Non-SMD) were found, low-to-moderate total sample correlations were demonstrated between the SRQ-Aversive sub-scale and i) PSQ total (r=0.31, psensory aspect of pain but weakly associated with the cognitive aspect. This indicates that SMD co-occurs with daily pain sensitivity, thus reducing QoL, but less with the cognitive-catastrophizing manifestation of pain perception. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Conditioned pain modulation in patients with nonspecific chronic back pain with chronic local pain, chronic widespread pain, and fibromyalgia.

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    Gerhardt, Andreas; Eich, Wolfgang; Treede, Rolf-Detlef; Tesarz, Jonas

    2017-03-01

    Findings considering conditioned pain modulation (CPM) in chronic back pain (CBP) are contradictory. This might be because many patients with CBP report pain in further areas of the body, and altered CPM might influence spatial extent of pain rather than CBP per se. Therefore, we compared CPM in patients with CBP with different pain extent. Patients with fibromyalgia syndrome (FMS), for whom CPM impairment is reported most consistently, were measured for comparison. Based on clinical evaluation and pain drawings, patients were categorized into chronic local back pain (CLP; n = 53), chronic widespread back pain (CWP; n = 32), and FMS (n = 92). Conditioned pain modulation was measured by the difference in pressure pain threshold (test stimuli) at the lower back before and after tonic heat pain (conditioning stimulus). We also measured psychosocial variables. Pressure pain threshold was significantly increased in CLP patients after tonic heat pain (P pain modulation in CLP was significantly higher than that in CWP and FMS (P painful areas (0-10) were associated with lower CPM (r = 0.346, P = 0.001) in CBP but not in FMS (r = -0.013, P = 0.903). Anxiety and depression were more pronounced in FMS than in CLP or CWP (P values pain inhibition seem to be more indicated the higher the pain extent.

  17. The impact of pain-related fear on neural pathways of pain modulation in chronic low back pain

    Directory of Open Access Journals (Sweden)

    Michael Lukas Meier

    2017-06-01

    Discussion:. Our findings might indicate a maladaptive psychobiological interaction in chronic LBP patients characterized by a disrupted amygdala-PAG-FC that is modulated by the degree of pain-related fear. These results shed new light on brain mechanisms underlying psychological factors that may have pronociceptive effects in chronic LBP.

  18. Medication overuse reinstates conditioned pain modulation in women with migraine.

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    Guy, Nathalie; Voisin, Daniel; Mulliez, Aurélien; Clavelou, Pierre; Dallel, Radhouane

    2018-05-01

    Background This study investigated the effects of medication overuse and withdrawal on modulation of pain processing in women with migraine. Temporal summation of laser-evoked thermal pain was used to measure the effects of conditioned pain modulation. Methods 36 female participants (12 healthy volunteers, 12 with episodic migraine and 12 with medication overuse headache) were included in a two session protocol. Medication overuse headache subjects were also tested three weeks after medication overuse headache withdrawal. Mechanical and laser-evoked thermal pain thresholds were measured on the back of the non-dominant hand where, later, temporal summation of laser-evoked thermal pain to repetitive thermal stimuli was elicited for 30 min, at an intensity producing moderate pain. Between the 10 th and 20 th minutes, the contralateral foot was immersed into a water bath at a not painful (30℃) or painfully cold (8℃; conditioned pain modulation) temperature. Results Episodic migraine, medication overuse headache and medication overuse headache withdrawal were associated with an increase in extracephalic temporal summation of laser-evoked thermal pain as compared to healthy volunteer subjects, while there was no alteration of laser-evoked thermal and mechanical extracephalic pain thresholds in these subjects. Conditioned pain modulation was highly efficient in temporal summation of laser-evoked thermal pain in healthy volunteer subjects, with a solid post-effect (reduction of pain). Conditioned pain modulation was still present, but reduced, in episodic migraine. By contrast, conditioned pain modulation was normal in medication overuse headache and strongly reduced in medication overuse headache withdrawal. Furthermore, in medication overuse headache withdrawal, the post-effect was no longer a decrease, but a facilitation of pain. Conclusions These data show that a decrease in conditioned pain modulation does not underlie medication overuse headache in women. On

  19. Descending inhibitory pain modulation is impaired in patients with chronic pancreatitis.

    NARCIS (Netherlands)

    Olesen, S.S.; Brock, C.; Krarup, A.L.; Funch-Jensen, P.; Arendt-Nielsen, L.; Wilder-Smith, O.H.G.; Drewes, A.M.

    2010-01-01

    BACKGROUND & AIMS: Pain is a prominent symptom in chronic pancreatitis (CP), but the underlying mechanisms are incompletely understood. We investigated the role of descending pain modulation from supraspinal structures as well as central nervous system sensitization in patients with pain from CP.

  20. Expectation violation and attention to pain jointly modulate neural gain in somatosensory cortex

    DEFF Research Database (Denmark)

    Fardo, Francesca; Auksztulewicz, Ryszard; Allen, Micah

    2017-01-01

    The neural processing and experience of pain are influenced by both expectations and attention. For example, the amplitude of event-related pain responses is enhanced by both novel and unexpected pain, and by moving the focus of attention towards a painful stimulus. Under predictive coding, this ...... the influence of both expectation violation and attention on cortical processing and pain perception.......The neural processing and experience of pain are influenced by both expectations and attention. For example, the amplitude of event-related pain responses is enhanced by both novel and unexpected pain, and by moving the focus of attention towards a painful stimulus. Under predictive coding......, this congruence can be explained by appeal to a precision-weighting mechanism, which mediates bottom-up and top-down attentional processes by modulating the influence of feedforward and feedback signals throughout the cortical hierarchy. The influence of expectation and attention on pain processing can thus...

  1. Effect of hypnotic pain modulation on brain activity in patients with temporomandibular disorder pain

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    Abrahamsen, Randi; Dietz, Martin; Lodahl, Sanne

    2010-01-01

    Hypnosis modulates pain perception but the associated brain mechanisms in chronic pain conditions are poorly understood. Brain activity evoked by painful repetitive pin-prick stimulation of the left mental nerve region was investigated with use of fMRI in 19 patients with painful temporomandibular...

  2. Evoked potentials after painful cutaneous electrical stimulation depict pain relief during a conditioned pain modulation.

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    Höffken, Oliver; Özgül, Özüm S; Enax-Krumova, Elena K; Tegenthoff, Martin; Maier, Christoph

    2017-08-29

    Conditioned pain modulation (CPM) evaluates the pain modulating effect of a noxious conditioning stimulus (CS) on another noxious test stimulus (TS), mostly based solely on subjective pain ratings. We used painful cutaneous electrical stimulation (PCES) to induce TS in a novel CPM-model. Additionally, to evaluate a more objective parameter, we recorded the corresponding changes of cortical evoked potentials (PCES-EP). We examined the CPM-effect in 17 healthy subjects in a randomized controlled cross-over design during immersion of the non-dominant hand into 10 °C or 24 °C cold water (CS). Using three custom-built concentric surface electrodes, electrical stimuli were applied on the dominant hand, inducing pain of 40-60 on NRS 0-100 (TS). At baseline, during and after CS we assessed the electrically induced pain intensity and electrically evoked potentials recorded over the central electrode (Cz). Only in the 10 °C-condition, both pain (52.6 ± 4.4 (baseline) vs. 30.3 ± 12.5 (during CS)) and amplitudes of PCES-EP (42.1 ± 13.4 μV (baseline) vs. 28.7 ± 10.5 μV (during CS)) attenuated during CS and recovered there after (all p pain ratings during electrical stimulation and amplitudes of PCES-EP correlated significantly with each other (r = 0.5) and with CS pain intensity (r = 0.5). PCES-EPs are a quantitative measure of pain relief, as changes in the electrophysiological response are paralleled by a consistent decrease in subjective pain ratings. This novel CPM paradigm is a feasible method, which could help to evaluate the function of the endogenous pain modulation processes. German Clinical Trials Register DRKS-ID: DRKS00012779 , retrospectively registered on 24 July 2017.

  3. Pain facilitation and pain inhibition during conditioned pain modulation in fibromyalgia and in healthy controls.

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    Potvin, Stéphane; Marchand, Serge

    2016-08-01

    Although fibromyalgia (FM) is associated with a deficit in inhibitory conditioned pain modulation (CPM), the discriminative power of CPM procedures is unknown. Moreover, the high intersubject heterogeneity in CPM responses in FM raises the possibility that a sizeable subgroup of these patients may experience pain facilitation during CPM, but the phenomenon has not been explicitly studied. To address these issues, 96 patients with FM and 71 healthy controls were recruited. Thermal stimuli were used to measure pain thresholds. Pain inhibition was elicited using a tonic thermal test (Peltier thermode) administered before and after activation of CPM mechanisms using a cold pressor test. Thermal pain thresholds were lower in patients with FM than in healthy controls. Pain ratings during the cold pressor test were higher in patients with FM, relative to controls. The CPM inhibitory efficacy was lower in patients with FM than in controls. The CPM procedure had good specificity (78.9%) but low sensitivity (45.7%), whereas a composite pain index had good sensitivity (75.0%) and specificity (78.9%). Finally, the rate of patients with FM who reported pain facilitation during the CPM procedure was found to be significantly increased compared with that of controls (41.7% vs 21.2%). The good discriminative power of the composite pain index highlights the need for further validation studies using mechanistically relevant psychophysical procedures in FM. The low sensitivity of the CPM procedure, combined with the large proportion of patients with FM experiencing pain facilitation during CPM, strongly suggests that endogenous pain inhibition mechanisms are deeply impaired in patients with FM, but only in a subgroup of them.

  4. Opposite Effects of Stress on Pain Modulation Depend on the Magnitude of Individual Stress Response.

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    Geva, Nirit; Defrin, Ruth

    2018-04-01

    The effect of acute stress on pain threshold and intolerance threshold are reported as producing either hypoalgesia or hyperalgesia. Yet, the contribution of individual stress reactivity in this respect has not been established. The aim was to test 2 pain modulation paradigms under acute stress manipulation, to our knowledge, for the first time, to study whether stress differentially affects pain modulation, and whether the effect is related to individual stress response. Participants were 31 healthy subjects. Conditioned pain modulation (CPM) and pain adaptation were measured before and after inducing an acute stress response using the Montreal Imaging Stress Task. Subjects' stress response was evaluated according to salivary cortisol, autonomic function, and perceived stress and anxiety. The Montreal Imaging Stress Task induced a validated stress response. On a group level, stress induced reduction in CPM magnitude and increase in pain adaptation compared with baseline. These responses correlated with stress reactivity. When the group was subdivided according to stress reactivity, only high stress responders exhibited reduced CPM whereas only low stress responders exhibited increased pain adaptation. The results suggest that acute stress may induce opposite effects on pain modulation, depending on individual stress reactivity magnitude, with an advantage to low stress responders. This study evaluated the effect of acute stress on pain modulation. Pain modulation under stress is affected by individual stress responsiveness; decreased CPM occurs in high stress responders whereas increased pain adaptation occurs in low stress responders. Identification of high stress responders may promote better pain management. Copyright © 2017 The American Pain Society. Published by Elsevier Inc. All rights reserved.

  5. Emotional modulation of pain and spinal nociception in fibromyalgia

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    Rhudy, Jamie L.; DelVentura, Jennifer L.; Terry, Ellen L.; Bartley, Emily J.; Olech, Ewa; Palit, Shreela; Kerr, Kara L.

    2013-01-01

    Fibromyalgia (FM) is characterized by widespread pain, as well as affective disturbance (e.g., depression). Given that emotional processes are known to modulate pain, a disruption of emotion and emotional modulation of pain and nociception may contribute to FM. The present study used a well-validated affective picture-viewing paradigm to study emotional processing and emotional modulation of pain and spinal nociception. Participants were 18 individuals with FM, 18 individuals with rheumatoid arthritis (RA), and 19 healthy pain-free controls (HC). Mutilation, neutral, and erotic pictures were presented in four blocks; two blocks assessed only physiological-emotional reactions (i.e., pleasure/arousal ratings, corrugator EMG, startle modulation, skin conductance) in the absence of pain and two blocks assessed emotional reactivity and emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception) evoked by suprathreshold electric stimulations over the sural nerve. In general, mutilation pictures elicited displeasure, corrugator activity, subjective arousal, and sympathetic activation, whereas erotic pictures elicited pleasure, subjective arousal, and sympathetic activation. However, FM was associated with deficits in appetitive activation (e.g., reduced pleasure/arousal to erotica). Moreover, emotional modulation of pain was observed in HC and RA, but not FM, even though all three groups evidenced modulation of NFR. Additionally, NFR thresholds were not lower in the FM group, indicating a lack of spinal sensitization. Together, these results suggest that FM is associated with a disruption of supraspinal processes associated with positive affect and emotional modulation of pain, but not brain-to-spinal cord circuitry that modulates spinal nociceptive processes. PMID:23622762

  6. Abdominal pain - children under age 12

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    Stomach pain in children; Pain - abdomen - children; Abdominal cramps in children; Belly ache in children ... When your child complains of abdominal pain, see if they can describe ... kinds of pain: Generalized pain or pain over more than half ...

  7. Short-term cortical plasticity induced by conditioning pain modulation

    DEFF Research Database (Denmark)

    Egsgaard, Line Lindhardt; Buchgreitz, Line; Wang, Li

    2012-01-01

    To investigate the effects of homotopic and heterotopic conditioning pain modulation (CPM) on short-term cortical plasticity. Glutamate (tonic pain) or isotonic saline (sham) was injected in the upper trapezius (homotopic) and in the thenar (heterotopic) muscles. Intramuscular electrical...... stimulation was applied to the trapezius at pain threshold intensities, and somatosensory evoked potentials were recorded with 128 channel EEG. Pain ratings were obtained during glutamate and sham pain injection. Short-term cortical plasticity to electrical stimulation was investigated before, during......300 z coordinate (P = 0.001) was found between glutamate versus sham pain (P = 0.009). This generator was located in the cingulate. A positive correlation at P300 between pain ratings to glutamate injection and the x coordinate during tonic pain (P = 0.016) was found for heterotopic CPM. Heterotopic...

  8. Contextual modulation of pain sensitivity utilising virtual environments.

    Science.gov (United States)

    Smith, Ashley; Carlow, Klancy; Biddulph, Tara; Murray, Brooke; Paton, Melissa; Harvie, Daniel S

    2017-05-01

    Investigating psychological mechanisms that modulate pain, such as those that might be accessed by manipulation of context, is of great interest to researchers seeking to better understand and treat pain. The aim of this study was to better understand the interaction between pain sensitivity, and contexts with inherent emotional and social salience - by exploiting modern immersive virtual reality (VR) technology. A within-subjects, randomised, double-blinded, repeated measures (RM) design was used. In total, 25 healthy participants were exposed to neutral, pleasant, threatening, socially positive and socially negative contexts, using an Oculus Rift DK2. Pressure pain thresholds (PPTs) were recorded in each context, as well as prior to and following the procedure. We also investigated whether trait anxiety and pain catastrophisation interacted with the relationship between the different contexts and pain. Pressure pain sensitivity was not modulated by context ( p  = 0.48). Anxiety and pain catastrophisation were not significantly associated with PPTs, nor did they interact with the relationship between context and PPTs. Contrary to our hypothesis, socially and emotionally salient contexts did not influence pain thresholds. In light of other research, we suggest that pain outcomes might only be tenable to manipulation by contextual cues if they specifically manipulate the meaning of the pain-eliciting stimulus, rather than manipulate psychological state generally - as per the current study. Future research might exploit immersive VR technology to better explore the link between noxious stimuli and contexts that directly alter its threat value.

  9. Induction and modulation of referred muscle pain in humans

    DEFF Research Database (Denmark)

    Laursen, René Johannes

    are needed. Spinal cord and higher centers are likely structures to study. The data presented in this thesis have made further contributions to understanding the mechanisms of muscle pain and RP that can be helpful in diagnosis, control, and treatment of muscle pain. Moreover, the intramuscular, electrical......Muscle pain is a major factor in many disorders such as injuries, degenerative diseases, and cancer. The mechanisms underlying muscle pain are not fully understood. A particular problem in muscle pain is the relationship between local and referred muscle pain. Experimental pain models are useful...... in basic pain research, because they allow a standardized activation of the nociceptive system and measurements of evoked responses. An electrical muscle pain model was constructed and applied on healthy subjects. The model was found suitable for inducing local (LP) and referred muscle pain (RF...

  10. 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.

  11. Expectation violation and attention to pain jointly modulate neural gain in somatosensory cortex.

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    Fardo, Francesca; Auksztulewicz, Ryszard; Allen, Micah; Dietz, Martin J; Roepstorff, Andreas; Friston, Karl J

    2017-06-01

    The neural processing and experience of pain are influenced by both expectations and attention. For example, the amplitude of event-related pain responses is enhanced by both novel and unexpected pain, and by moving the focus of attention towards a painful stimulus. Under predictive coding, this congruence can be explained by appeal to a precision-weighting mechanism, which mediates bottom-up and top-down attentional processes by modulating the influence of feedforward and feedback signals throughout the cortical hierarchy. The influence of expectation and attention on pain processing can be mapped onto changes in effective connectivity between or within specific neuronal populations, using a canonical microcircuit (CMC) model of hierarchical processing. We thus implemented a CMC within dynamic causal modelling for magnetoencephalography in human subjects, to investigate how expectation violation and attention to pain modulate intrinsic (within-source) and extrinsic (between-source) connectivity in the somatosensory hierarchy. This enabled us to establish whether both expectancy and attentional processes are mediated by a similar precision-encoding mechanism within a network of somatosensory, frontal and parietal sources. We found that both unexpected and attended pain modulated the gain of superficial pyramidal cells in primary and secondary somatosensory cortex. This modulation occurred in the context of increased lateralized recurrent connectivity between somatosensory and fronto-parietal sources, driven by unexpected painful occurrences. Finally, the strength of effective connectivity parameters in S1, S2 and IFG predicted individual differences in subjective pain modulation ratings. Our findings suggest that neuromodulatory gain control in the somatosensory hierarchy underlies the influence of both expectation violation and attention on cortical processing and pain perception. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Pain Perception Can Be Modulated by Mindfulness Training: A Resting-state fMRI Study

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    I-Wen Su

    2016-11-01

    Full Text Available The multi-dimensional nature of pain renders difficult a holistic understanding of it. The conceptual framework of pain is said to be cognitive-evaluative, in addition to being sensory-discriminative and affective-motivational. To compare participants’ brain-behavior response before and after a six-week mindfulness-based stress reduction (MBSR training course on mindfulness in relation to pain modulation, three questionnaires (the Dallas Pain Questionnaire, Short Form McGill Pain Questionnaire-SFMPQ, and Kentucky Inventory of Mindfulness as well as resting-state functional magnetic resonance imaging (fMRI were administered to participants, divided into a pain-afflicted group (N=18 and a control group (N=16. Our results showed that the pain-afflicted group experienced significantly less pain after the mindfulness treatment than before, as measured by the SFMPQ. In conjunction, an increased connection from the anterior insular cortex (AIC to the dorsal anterior midcingulate cortex (daMCC was observed in the post-training pain-afflicted group and a significant correlation was found between AIC-daMCC connectivity and SFMPQ scores. The results suggest that mindfulness training can modulate the brain network dynamics underlying the subjective experience of pain.

  13. Deficient conditioned pain modulation after spinal cord injury correlates with clinical spontaneous pain measures.

    Science.gov (United States)

    Albu, Sergiu; Gómez-Soriano, Julio; Avila-Martin, Gerardo; Taylor, Julian

    2015-02-01

    The contribution of endogenous pain modulation dysfunction to clinical and sensory measures of neuropathic pain (NP) has not been fully explored. Habituation, temporal summation, and heterotopic noxious conditioning stimulus-induced modulation of tonic heat pain intensity were examined in healthy noninjured subjects (n = 10), and above the level of spinal cord injury (SCI) in individuals without (SCI-noNP, n = 10) and with NP (SCI-NP, n = 10). Thermoalgesic thresholds, Cz/AFz contact heat evoked potentials (CHEPs), and phasic or tonic (30 seconds) heat pain intensity were assessed within the C6 dermatome. Although habituation to tonic heat pain intensity (0-10) was reported by the noninjured (10 s: 3.5 ± 0.3 vs 30 s: 2.2 ± 0.5 numerical rating scale; P = 0.003), loss of habituation was identified in both the SCI-noNP (3.8 ± 0.3 vs 3.6 ± 0.5) and SCI-NP group (4.2 ± 0.4 vs 4.9 ± 0.8). Significant temporal summation of tonic heat pain intensity was not observed in the 3 groups. Inhibition of tonic heat pain intensity induced by heterotopic noxious conditioning stimulus was identified in the noninjured (-29.7% ± 9.7%) and SCI-noNP groups (-19.6% ± 7.0%), but not in subjects with SCI-NP (+1.1% ± 8.0%; P P = 0.015) and evoked heat pain intensity (ρ = 0.8; P = 0.007) in the SCI-NP group. Stepwise regression analysis revealed that the mean conditioned pain modulation (R = 0.72) correlated with pain severity and pressing spontaneous pain in the SCI-NP group. Comprehensive assessment of sensory dysfunction above the level of injury with tonic thermal test and conditioning stimuli revealed less-efficient endogenous pain modulation in subjects with SCI-NP.

  14. Pain-related emotions modulate experimental pain perception and autonomic responses.

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    Rainville, Pierre; Bao, Quoc Viet Huynh; Chrétien, Pablo

    2005-12-05

    The effect of emotions on pain perception is generally recognized but the underlying mechanisms remain unclear. Here, emotions related to pain were induced in healthy volunteers using hypnosis, during 1-min immersions of the hand in painfully hot water. In Experiment 1, hypnotic suggestions were designed to induce various positive or negative emotions. Compared to a control condition with hypnotic-relaxation, negative emotions produced robust increases in pain. In Experiment 2, induction of pain-related anger and sadness were found to increase pain. Pain increases were associated with increases in self-rated desire for relief and decreases in expectation of relief, and with increases in arousal, negative affective valence and decreases in perceived control. In Experiment 3, hypnotic suggestions specifically designed to increase and decrease the desire for relief produced increases and decreases in pain, respectively. In all three experiments, emotion-induced changes in pain were most consistently found on ratings of pain unpleasantness compared to pain intensity. Changes in pain-evoked cardiac responses (R-R interval decrease), measured in experiments 2 and 3, were consistent with changes in pain unpleasantness. Correlation and multiple regression analyses suggest that negative emotions and desire for relief influence primarily pain affect and that pain-evoked autonomic responses are strongly associated with pain affect. These results confirm the hypothesized influence of the desire for relief on pain perception, and particularly on pain affect, and support the functional relation between pain affect and autonomic nociceptive responses. This study provides further experimental confirmation that pain-related emotions influence pain perception and pain-related physiological responses.

  15. Reward Circuitry Plasticity in Pain Perception and Modulation

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    Marcos F. DosSantos

    2017-11-01

    Full Text Available Although pain is a widely known phenomenon and an important clinical symptom that occurs in numerous diseases, its mechanisms are still barely understood. Owing to the scarce information concerning its pathophysiology, particularly what is involved in the transition from an acute state to a chronic condition, pain treatment is frequently unsatisfactory, therefore contributing to the amplification of the chronic pain burden. In fact, pain is an extremely complex experience that demands the recruitment of an intricate set of central nervous system components. This includes cortical and subcortical areas involved in interpretation of the general characteristics of noxious stimuli. It also comprises neural circuits that process the motivational-affective dimension of pain. Hence, the reward circuitry represents a vital element for pain experience and modulation. This review article focuses on the interpretation of the extensive data available connecting the major components of the reward circuitry to pain suffering, including the nucleus accumbens, ventral tegmental area, and the medial prefrontal cortex; with especial attention dedicated to the evaluation of neuroplastic changes affecting these structures found in chronic pain syndromes, such as migraine, trigeminal neuropathic pain, chronic back pain, and fibromyalgia.

  16. Orienting Attention Modulates Pain Perception: An ERP Study

    Science.gov (United States)

    Chan, Sam C. C.; Chan, Chetwyn C. H.; Kwan, Anne S. K.; Ting, Kin-hung; Chui, Tak-yi

    2012-01-01

    Introduction Research has shown that people with chronic pain have difficulty directing their attention away from pain. A mental strategy that incorporates focused attention and distraction has been found to modulate the perception of pain intensity. That strategy involves placing attention on the nociceptive stimulus felt and shifting attention to a self-generated sub-nociceptive image and rehearsing it. Event-related potential was used to study the possible processes associated with the focus-then-orient strategy. Methods Eighteen pain-free participants received different levels of 50-ms nociceptive stimulations elicited by electric shocks at the right lateral malleolus (ankle). In perception trials, participants maintained the perceived nociceptive stimulus in working memory for 3,000 ms. In imagery trials, participants mentally generated and maintained the corresponding sub-nociceptive image they had learned previously. After both types of trials, participants evaluated the pain intensity of the incoming stimulus by recalling the feeling of the nociceptive stimulation at the beginning of the trial. Results Shifting attention from the incoming nociceptive to a self-generated sub-nociceptive image elicited central P2 and centro-parietal P3 waves, which were found to correlate with proportional scores on the Stroop Test. They were followed by a frontal N400 and a parietal P600, denoting generation of sub-nociceptive images in working memory. The voltages elicited in these potentials correlated moderately with attenuation of the pain ratings of the recalled nociceptive stimulations. Conclusions Focus-and-orient attention across nociceptive and sub-nociceptive images appears to be related to response inhibition. Mental rehearsal of the sub-nociceptive images was found to modulate the perception of the nociceptive sensation felt prior to the imagery. Such modulation seems to be mediated by generating and maintaining sub-nociceptive images in working memory. Future

  17. Orienting attention modulates pain perception: an ERP study.

    Directory of Open Access Journals (Sweden)

    Sam C C Chan

    Full Text Available INTRODUCTION: Research has shown that people with chronic pain have difficulty directing their attention away from pain. A mental strategy that incorporates focused attention and distraction has been found to modulate the perception of pain intensity. That strategy involves placing attention on the nociceptive stimulus felt and shifting attention to a self-generated sub-nociceptive image and rehearsing it. Event-related potential was used to study the possible processes associated with the focus-then-orient strategy. METHODS: Eighteen pain-free participants received different levels of 50-ms nociceptive stimulations elicited by electric shocks at the right lateral malleolus (ankle. In perception trials, participants maintained the perceived nociceptive stimulus in working memory for 3,000 ms. In imagery trials, participants mentally generated and maintained the corresponding sub-nociceptive image they had learned previously. After both types of trials, participants evaluated the pain intensity of the incoming stimulus by recalling the feeling of the nociceptive stimulation at the beginning of the trial. RESULTS: Shifting attention from the incoming nociceptive to a self-generated sub-nociceptive image elicited central P2 and centro-parietal P3 waves, which were found to correlate with proportional scores on the Stroop Test. They were followed by a frontal N400 and a parietal P600, denoting generation of sub-nociceptive images in working memory. The voltages elicited in these potentials correlated moderately with attenuation of the pain ratings of the recalled nociceptive stimulations. CONCLUSIONS: Focus-and-orient attention across nociceptive and sub-nociceptive images appears to be related to response inhibition. Mental rehearsal of the sub-nociceptive images was found to modulate the perception of the nociceptive sensation felt prior to the imagery. Such modulation seems to be mediated by generating and maintaining sub-nociceptive images in

  18. 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...

  19. Pain by Association? Experimental Modulation of Human Pain Thresholds Using Classical Conditioning.

    Science.gov (United States)

    Madden, Victoria J; Bellan, Valeria; Russek, Leslie N; Camfferman, Danny; Vlaeyen, Johan W S; Moseley, G Lorimer

    2016-10-01

    A classical conditioning framework is often used for clinical reasoning about pain that persists after tissue healing. However, experimental studies demonstrating classically conditioned pain in humans are lacking. The current study tested whether non-nociceptive somatosensory stimuli can come to modulate pain thresholds after being paired with painful nociceptive stimuli in healthy humans. We used a differential simultaneous conditioning paradigm in which one nonpainful vibrotactile conditioned stimulus (CS(+)) was simultaneously paired with an unconditioned painful laser stimulus, and another vibrotactile stimulus (CS(-)) was paired with a nonpainful laser stimulus. After acquisition, at-pain-threshold laser stimuli were delivered simultaneously with a CS(+) or CS(-) vibrotactile stimulus. The primary outcome was the percentage of at-threshold laser stimuli that were reported as painful. The results were as expected: after conditioning, at-threshold laser trials paired with the CS(+) were reported as painful more often, as more intense, and as more unpleasant than those paired with the CS(-). This study provides new evidence that pain thresholds can be modulated via classical conditioning, even when the stimulus used to test the threshold cannot be anticipated. As such, it lays a critical foundation for further investigations of classical conditioning as a possible driver of persistent pain. This study provides new evidence that human pain thresholds can be influenced by non-nociceptive somatosensory stimuli, via a classical conditioning effect. As such, it lays a critical foundation for further investigations of classical conditioning as a possible driver of persistent pain. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  20. Sex differences in the relationship between maternal fear of pain and children's conditioned pain modulation

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    Evans S

    2013-03-01

    Full Text Available Subhadra Evans, Laura C Seidman, Kirsten C Lung, Lonnie K Zeltzer, Jennie C TsaoPediatric Pain Program, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USABackground: Parental behaviors, emotions, and cognitions are known to influence children's response to pain. However, prior work has not tested the association between maternal psychological factors and children's responses to a conditioned pain modulation (CPM task. CPM refers to the reduction in perceived pain intensity for a test stimulus following application of a conditioning stimulus to a remote area of the body, and is thought to reflect the descending inhibition of nociceptive signals.Methods: The present study examined sex differences in the association between maternal anxiety about pain and children's CPM responses in 133 healthy children aged 8–17 years. Maternal pain anxiety was assessed using the Pain Anxiety Symptoms Scale-20. In addition to the magnitude of CPM, children's anticipatory anxiety and pain-related fear of the CPM task were measured.Results: Sequential multiple linear regression revealed that even after controlling for child age and general maternal psychological distress, greater maternal pain anxiety was significantly related to greater CPM anticipatory anxiety and pain-related fear in girls, and to less CPM (ie, less pain inhibition in boys.Conclusion: The findings indicate sex-specific relationships between maternal pain anxiety and children's responses to a CPM task over and above that accounted for by the age of the child and the mother's general psychological distress.Keywords: diffuse noxious inhibitory controls, pediatric pain, mother-child relationship, cold pressor, pressure pain, laboratory pain

  1. Conditioned Pain Modulation and Pressure Pain Sensitivity in the Adult Danish General Population

    DEFF Research Database (Denmark)

    Skovbjerg, Sine; Jørgensen, Torben; Arendt-Nielsen, Lars

    2017-01-01

    Increased pressure pain sensitivity and impaired descending pain control have been associated with chronic pain, but knowledge on the variability in the adult general population is lacking. Pressure pain thresholds (PPTs) and descending pain control assessed using conditioned pain modulation (CPM......) were recorded in a randomly selected sample (n = 2,199, 53% female) of the Danish adult general population aged 18 to 70 years. PPTs were recorded over the tibialis anterior muscle and the upper trapezius muscle. CPM was defined as the difference between PPT assessments before and during conditioning...... was associated with lower PPTs (P CPM potency was lower in female compared with male participants (P ≤ .003), whereas no association with age was found. Higher level of education (P ≤ .05), premature withdrawal from the cold pressor test...

  2. Dissociating nociceptive modulation by the duration of pain anticipation from unpredictability in the timing of pain.

    Science.gov (United States)

    Clark, Jennifer A; Brown, Christopher A; Jones, Anthony K P; El-Deredy, Wael

    2008-12-01

    Waiting longer to receive pain increases its perceived unpleasantness by inducing 'dread'. However, it is not clear how unpredictability in the timing of the impending pain stimulus interacts with dread and whether the two factors show differential effects on the neural generators of the pain-evoked response. We manipulated the duration of anticipation of laser-induced pain independently of unpredictability of stimulus delivery timing, to observe the relative effect on P2 amplitudes of the laser-evoked potential (LEP) response and its estimated sources. Subjects (n=12) reported increased pain ratings after longer pain anticipation, irrespective of unpredictability in the timing of stimulus delivery. By contrast, unpredictability in stimulus timing increased the amplitude of the P2 irrespective of anticipation duration. The modulation of P2 amplitude by unpredictability was localized to midcingulate cortex (MCC) and ipsilateral secondary somatosensory (S2) areas. Greater anticipation duration increased activity in a hippocampal-insula-prefrontal network but not in MCC areas. Distinct neural networks contribute to the P2 and are differentially affected by pain anticipation duration and unpredictability in stimulus timing. ERP research into dread should be careful to appreciate the neural generators of pain-evoked responses and their potential modulation by unpredictability.

  3. Music modulation of pain perception and pain-related activity in the brain, brain stem, and spinal cord: a functional magnetic resonance imaging study.

    Science.gov (United States)

    Dobek, Christine E; Beynon, Michaela E; Bosma, Rachael L; Stroman, Patrick W

    2014-10-01

    The oldest known method for relieving pain is music, and yet, to date, the underlying neural mechanisms have not been studied. Here, we investigate these neural mechanisms by applying a well-defined painful stimulus while participants listened to their favorite music or to no music. Neural responses in the brain, brain stem, and spinal cord were mapped with functional magnetic resonance imaging spanning the cortex, brain stem, and spinal cord. Subjective pain ratings were observed to be significantly lower when pain was administered with music than without music. The pain stimulus without music elicited neural activity in brain regions that are consistent with previous studies. Brain regions associated with pleasurable music listening included limbic, frontal, and auditory regions, when comparing music to non-music pain conditions. In addition, regions demonstrated activity indicative of descending pain modulation when contrasting the 2 conditions. These regions include the dorsolateral prefrontal cortex, periaqueductal gray matter, rostral ventromedial medulla, and dorsal gray matter of the spinal cord. This is the first imaging study to characterize the neural response of pain and how pain is mitigated by music, and it provides new insights into the neural mechanism of music-induced analgesia within the central nervous system. This article presents the first investigation of neural processes underlying music analgesia in human participants. Music modulates pain responses in the brain, brain stem, and spinal cord, and neural activity changes are consistent with engagement of the descending analgesia system. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

  4. Social modulation of and by pain in humans and rodents.

    Science.gov (United States)

    Mogil, Jeffrey S

    2015-04-01

    The social domain of the biopsychosocial model of pain has been greatly understudied compared with the biological and psychological domains but holds great promise for furthering our understanding, and better treatment, of pain. Recent years have seen an explosion of interest in social neuroscience and have revealed the ability of pain stimuli to alter social interactions. These experiments suggest that rodents are capable of producing simplified versions of any number of social phenomena involving empathy, previously thought to be the sole province of human beings. This review describes the state of science in both humans and nonhuman animals, and notes intriguing parallels in observations from both species. Indeed, my laboratory is starting to demonstrate perfectly translatable findings regarding social modulation of pain in rodents and humans.

  5. 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.

  6. Influence of Dopaminergic Medication on Conditioned Pain Modulation in Parkinson's Disease Patients.

    Directory of Open Access Journals (Sweden)

    Wiebke Grashorn

    Full Text Available Pain is highly prevalent in patients with Parkinson's disease (PD, but little is known about the underlying pathophysiological mechanisms. The susceptibility to pain is known to depend on ascending and descending pathways. Because parts of the descending pain inhibitory system involve dopaminergic pathways, dysregulations in dopaminergic transmission might contribute to altered pain processing in PD. Deficits in endogenous pain inhibition can be assessed using conditioned pain modulation (CPM paradigms.Applying such a paradigm, we investigated i whether CPM responses differ between PD patients and healthy controls, ii whether they are influenced by dopaminergic medication and iii whether there are effects of disease-specific factors. 25 patients with idiopathic PD and 30 healthy age- and gender-matched controls underwent an established CPM paradigm combining heat pain test stimuli at the forearm and the cold pressor task on the contralateral foot as the conditioning stimulus. PD patients were tested under dopaminergic medication and after at least 12 hours of medication withdrawal.No significant differences between CPM responses of PD patients and healthy controls or between PD patients "on" and "off" medication were found. These findings suggest (i that CPM is insensitive to dopaminergic modulations and (ii that PD is not related to general deficits in descending pain inhibition beyond the known age-related decline. However, at a trend level, we found differences between PD subtypes (akinetic-rigid, tremor-dominant, mixed with the strongest impairment of pain inhibition in the akinetic-rigid subtype.There were no significant differences between CPM responses of patients compared to healthy controls or between patients "on" and "off" medication. Differences between PD subtypes at a trend level point towards different pathophysiological mechanisms underlying the three PD subtypes which warrant further investigation and potentially differential

  7. Catastrophizing Interferes with Cognitive Modulation of Pain in Women with Fibromyalgia.

    Science.gov (United States)

    Ellingson, Laura D; Stegner, Aaron J; Schwabacher, Isaac J; Lindheimer, Jacob B; Cook, Dane B

    2018-02-21

    Pain modulation is a critical function of the nociceptive system that includes the ability to engage descending pain control systems to maintain a functional balance between facilitation and inhibition of incoming sensory stimuli. Dysfunctional pain modulation is associated with increased risk for chronic pain and is characteristic of fibromyalgia (FM). Catastrophizing is also common in FM. However, its influence on pain modulation is poorly understood. To determine the role of catastrophizing on central nervous system processing during pain modulation in FM via examining brain responses and pain sensitivity during an attention-distraction paradigm. Twenty FM patients and 18 healthy controls (CO) underwent functional magnetic resonance imaging while receiving pain stimuli, administered alone and during distracting cognitive tasks. Pain ratings were assessed after each stimulus. Catastrophizing was assessed with the Pain Catastrophizing Scale (PCS). The ability to modulate pain during distraction varied among FM patients and was associated with catastrophizing. This was demonstrated by significant positive relationships between PCS scores and pain ratings (P modulation did not differ between FM and CO (P > 0.05). FM patients with higher levels of catastrophizing were less able to distract themselves from pain, indicative of catastrophizing-related impairments in pain modulation. These results suggest that the tendency to catastrophize interacts with attention-resource allocation and may represent a mechanism of chronic pain exacerbation and/or maintenance. Reducing catastrophizing may improve FM symptoms via improving central nervous system regulation of pain.

  8. Conditioned pain modulation and situational pain catastrophizing as preoperative predictors of pain following chest wall surgery: a prospective observational cohort study.

    Directory of Open Access Journals (Sweden)

    Kasper Grosen

    Full Text Available Variability in patients' postoperative pain experience and response to treatment challenges effective pain management. Variability in pain reflects individual differences in inhibitory pain modulation and psychological sensitivity, which in turn may be clinically relevant for the disposition to acquire pain. The aim of this study was to investigate the effects of conditioned pain modulation and situational pain catastrophizing on postoperative pain and pain persistency.Preoperatively, 42 healthy males undergoing funnel chest surgery completed the Spielberger's State-Trait Anxiety Inventory and Beck's Depression Inventory before undergoing a sequential conditioned pain modulation paradigm. Subsequently, the Pain Catastrophizing Scale was introduced and patients were instructed to reference the conditioning pain while answering. Ratings of movement-evoked pain and consumption of morphine equivalents were obtained during postoperative days 2-5. Pain was reevaluated at six months postoperatively.Patients reporting persistent pain at six months follow-up (n = 15 were not significantly different from pain-free patients (n = 16 concerning preoperative conditioned pain modulation response (Z = 1.0, P = 0.3 or level of catastrophizing (Z = 0.4, P = 1.0. In the acute postoperative phase, situational pain catastrophizing predicted movement-evoked pain, independently of anxiety and depression (β = 1.0, P = 0.007 whereas conditioned pain modulation predicted morphine consumption (β = -0.005, P = 0.001.Preoperative conditioned pain modulation and situational pain catastrophizing were not associated with the development of persistent postoperative pain following funnel chest repair. Secondary outcome analyses indicated that conditioned pain modulation predicted morphine consumption and situational pain catastrophizing predicted movement-evoked pain intensity in the acute postoperative phase. These findings may have

  9. Effect of pain chronification and chronic pain on an endogenous pain modulation circuit in rats.

    Science.gov (United States)

    Miranda, J; Lamana, S M S; Dias, E V; Athie, M; Parada, C A; Tambeli, C H

    2015-02-12

    We tested the hypothesis that chronic pain development (pain chronification) and ongoing chronic pain (chronic pain) reduce the activity and induce plastic changes in an endogenous analgesia circuit, the ascending nociceptive control. An important mechanism mediating this form of endogenous analgesia, referred to as capsaicin-induced analgesia, is its dependence on nucleus accumbens μ-opioid receptor mechanisms. Therefore, we also investigated whether pain chronification and chronic pain alter the requirement for nucleus accumbens μ-opioid receptor mechanisms in capsaicin-induced analgesia. We used an animal model of pain chronification in which daily subcutaneous prostaglandin E2 (PGE2) injections into the rat's hind paw for 14 days, referred to as the induction period of persistent hyperalgesia, induce a long-lasting state of nociceptor sensitization referred to as the maintenance period of persistent hyperalgesia, that lasts for at least 30 days following the cessation of the PGE2 treatment. The nociceptor hypersensitivity was measured by the shortening of the time interval for the animal to respond to a mechanical stimulation of the hind paw. We found a significant reduction in the duration of capsaicin-induced analgesia during the induction and maintenance period of persistent mechanical hyperalgesia. Intra-accumbens injection of the μ-opioid receptor selective antagonist Cys(2),Tyr(3),Orn(5),Pen(7)amide (CTOP) 10 min before the subcutaneous injection of capsaicin into the rat's fore paw blocked capsaicin-induced analgesia. Taken together, these findings indicate that pain chronification and chronic pain reduce the duration of capsaicin-induced analgesia, without affecting its dependence on nucleus accumbens μ-opioid receptor mechanisms. The attenuation of endogenous analgesia during pain chronification and chronic pain suggests that endogenous pain circuits play an important role in the development and maintenance of chronic pain. Copyright © 2014 IBRO

  10. Acute Psychosocial Stress and Emotion Regulation Skills Modulate Empathic Reactions to Pain in Others

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    Gabriele eBuruck

    2014-05-01

    Full Text Available Psychosocial stress affects resources for adequate coping with environmental demands. A crucial question in this context is the extent to which acute psychosocial stressors impact empathy and emotion regulation. In the present study, 120 participants were randomly assigned to a control group vs. a group confronted with the Trier Social Stress Test, an established paradigm for the induction of acute psychosocial stress. Empathy for pain as a specific subgroup of empathy was assessed via pain intensity ratings during a pain-picture task. Self-reported emotion regulation skills were measured as predictors using an established questionnaire. Stressed individuals scored significantly lower on the appraisal of pain pictures. A regression model was chosen to find variables that further predict the pain ratings. These findings implicate that acute psychosocial stress might impair empathic processes to observed pain in another person and the ability to accept one’s emotion additionally predicts the empathic reaction. Furthermore, the ability to tolerate negative emotions modulated the relation between stress and pain judgments, and thus influenced core cognitive-affective functions relevant for coping with environmental challenges. In conclusion, our study emphasizes the necessity of reducing negative emotions in terms of empathic distress when confronted with pain of another person under psychosocial stress, in order to be able to retain pro-social behavior.

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

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    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.

  12. Bacteria activate sensory neurons that modulate pain and inflammation.

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    Chiu, Isaac M; Heesters, Balthasar A; Ghasemlou, Nader; Von Hehn, Christian A; Zhao, Fan; Tran, Johnathan; Wainger, Brian; Strominger, Amanda; Muralidharan, Sriya; Horswill, Alexander R; Bubeck Wardenburg, Juliane; Hwang, Sun Wook; Carroll, Michael C; Woolf, Clifford J

    2013-09-05

    Nociceptor sensory neurons are specialized to detect potentially damaging stimuli, protecting the organism by initiating the sensation of pain and eliciting defensive behaviours. Bacterial infections produce pain by unknown molecular mechanisms, although they are presumed to be secondary to immune activation. Here we demonstrate that bacteria directly activate nociceptors, and that the immune response mediated through TLR2, MyD88, T cells, B cells, and neutrophils and monocytes is not necessary for Staphylococcus aureus-induced pain in mice. Mechanical and thermal hyperalgesia in mice is correlated with live bacterial load rather than tissue swelling or immune activation. Bacteria induce calcium flux and action potentials in nociceptor neurons, in part via bacterial N-formylated peptides and the pore-forming toxin α-haemolysin, through distinct mechanisms. Specific ablation of Nav1.8-lineage neurons, which include nociceptors, abrogated pain during bacterial infection, but concurrently increased local immune infiltration and lymphadenopathy of the draining lymph node. Thus, bacterial pathogens produce pain by directly activating sensory neurons that modulate inflammation, an unsuspected role for the nervous system in host-pathogen interactions.

  13. How diagnostic tests help to disentangle the mechanisms underlying neuropathic pain symptoms in painful neuropathies.

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    Truini, Andrea; Cruccu, Giorgio

    2016-02-01

    Neuropathic pain, ie, pain arising directly from a lesion or disease affecting the somatosensory afferent pathway, manifests with various symptoms, the commonest being ongoing burning pain, electrical shock-like sensations, and dynamic mechanical allodynia. Reliable insights into the mechanisms underlying neuropathic pain symptoms come from diagnostic tests documenting and quantifying somatosensory afferent pathway damage in patients with painful neuropathies. Neurophysiological investigation and skin biopsy studies suggest that ongoing burning pain primarily reflects spontaneous activity in nociceptive-fiber pathways. Electrical shock-like sensations presumably arise from high-frequency ectopic bursts generated in demyelinated, nonnociceptive, Aβ fibers. Although the mechanisms underlying dynamic mechanical allodynia remain debatable, normally innocuous stimuli might cause pain by activating spared and sensitized nociceptive afferents. Extending the mechanistic approach to neuropathic pain symptoms might advance targeted therapy for the individual patient and improve testing for new drugs.

  14. [Pathophysiology of neuropathic pain: molecular mechanisms underlying central sensitization in the dorsal horn in neuropathic pain].

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    Yamanaka, Hiroki; Noguchi, Koichi

    2012-11-01

    Neuropathic pain syndromes are clinically characterized by spontaneous pain and evoked pain (hyperalgesia and allodynia). The optimal treatment approach for neuropathic pain is still under development because of the complex pathological mechanisms underlying this type of pain. The spinal cord is an important gateway thorough which peripheral pain signals are transmitted to the brain, and sensitization of the spinal neurons is one of the important mechanisms underlying neuropathic pain. Central sensitization represents enhancement of the function of neuronal circuits in nociceptive pathways and is a manifestation of the remarkable plasticity of the somatosensory nervous system after nerve injury. This review highlights the pathological features of central sensitization, which develops because of (1) injury-induced abnormal inputs from primary afferents, (2) increase in the excitability of dorsal horn neurons, and (3) activated glial cell-derived signals.

  15. 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....

  16. A novel paradigm to evaluate conditioned pain modulation in fibromyalgia

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    Schoen CJ

    2016-09-01

    Full Text Available Cynthia J Schoen,1,* Jacob N Ablin,2,* Eric Ichesco,1 Rupal J Bhavsar,3 Laura Kochlefl,1 Richard E Harris,1 Daniel J Clauw,1 Richard H Gracely,4 Steven E Harte1 1Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, MI, USA; 2Institute of Rheumatology, Tel Aviv Suorasky Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Department of Neurology, University of Pennsylvania, Philadelphia, PA, 4Department of Endodontics, University of North Carolina – Chapel Hill, Chapel Hill, NC, USA *These authors contributed equally to this work Introduction: Application of noxious stimulation to one body area reduces pain sensitivity in a remote body area through activation of an endogenous pain-inhibitory network, a behavioral phenomenon referred to as conditioned pain modulation (CPM. The efficiency of CPM is predictive of a variety of health outcomes, while impaired CPM has been associated with various chronic pain conditions. Current methods used to assess CPM vary widely, and interest in CPM method development remains strong. Here, we evaluated a novel method for assessing CPM in healthy controls and fibromyalgia (FM patients using thumb pressure as both a test and conditioning stimulus.Methods: Sixteen female FM patients and 14 matched healthy controls underwent CPM testing with thumbnail pressure as the test stimulus, and either cold water or noxious pressure as the conditioning stimulus. CPM magnitude was evaluated as the difference in pain rating of the test stimulus applied before and during the conditioning stimulus.Results: In healthy controls, application of either pressure or cold water conditioning stimulation induced CPM as evidenced by a significant reduction in test stimulus pain rating during conditioning (P=0.007 and P=0.021, respectively. In contrast, in FM patients, neither conditioning stimulus induced a significant CPM effect P-values >0

  17. Cognitive modulation of pain and predictive coding. Comment on “Facing the experience of pain: A neuropsychological perspective” by Fabbro and Crescentini

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    Pagnoni, Giuseppe; Porro, Carlo A.

    2014-09-01

    Pain is a phenomenologically complex experience whose sensory and psychological dimensions are deeply intertwined. In their perspective article, Fabbro and Crescentini [1] review the physiological and neural mechanisms underlying nociception and its cognitive modulation within the broader concept of suffering, which includes psychological pain [2] in its culturally mediated and existentially nuanced forms. The tight link between affective and cognitive processes, on the one hand, and pain, on the other, is illustrated by examining in turn the placebo effect, empathy for other people's afflictions, clinical depression, and the role that mindfulness-based practices may play in alleviating suffering.

  18. Reliability of conditioned pain modulation: a systematic review

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    Kennedy, Donna L.; Kemp, Harriet I.; Ridout, Deborah; Yarnitsky, David; Rice, Andrew S.C.

    2016-01-01

    Abstract A systematic literature review was undertaken to determine if conditioned pain modulation (CPM) is reliable. Longitudinal, English language observational studies of the repeatability of a CPM test paradigm in adult humans were included. Two independent reviewers assessed the risk of bias in 6 domains; study participation; study attrition; prognostic factor measurement; outcome measurement; confounding and analysis using the Quality in Prognosis Studies (QUIPS) critical assessment tool. Intraclass correlation coefficients (ICCs) less than 0.4 were considered to be poor; 0.4 and 0.59 to be fair; 0.6 and 0.75 good and greater than 0.75 excellent. Ten studies were included in the final review. Meta-analysis was not appropriate because of differences between studies. The intersession reliability of the CPM effect was investigated in 8 studies and reported as good (ICC = 0.6-0.75) in 3 studies and excellent (ICC > 0.75) in subgroups in 2 of those 3. The assessment of risk of bias demonstrated that reporting is not comprehensive for the description of sample demographics, recruitment strategy, and study attrition. The absence of blinding, a lack of control for confounding factors, and lack of standardisation in statistical analysis are common. Conditioned pain modulation is a reliable measure; however, the degree of reliability is heavily dependent on stimulation parameters and study methodology and this warrants consideration for investigators. The validation of CPM as a robust prognostic factor in experimental and clinical pain studies may be facilitated by improvements in the reporting of CPM reliability studies. PMID:27559835

  19. What Are the Predictors of Altered Central Pain Modulation in Chronic Musculoskeletal Pain Populations? A Systematic Review.

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    Clark, Jacqui; Nijs, Jo; Yeowell, Gillian; Goodwin, Peter Charles

    2017-09-01

    Altered central pain modulation is the predominant pain mechanism in a proportion of chronic musculoskeletal pain disorders and is associated with poor outcomes. Although existing studies predict poor outcomes such as persistent pain and disability, to date there is little consensus on what factors specifically predict altered central pain modulation. To review the existing literature on the predictive factors specifically for altered central pain modulation in musculoskeletal pain populations. This is a systematic review in accordance with supplemented PRISMA guidelines. A systematic search was performed by 2 mutually blinded reviewers. Relevant articles were screened by title and abstract from Medline, Embase, PubMed, CINAHL, and Web of Science electronic databases. Alternative sources were also sought to locate missed potential articles. Eligibility included studies published in English, adults aged 18 to 65, musculoskeletal pain, baseline measurements taken at the pre-morbid or acute stage, > 3-month follow-up time after pain onset, and primary outcome measures specific to altered central pain modulation. Studies were excluded where there were concurrent diseases or they were non-predictive studies. Risk of bias was assessed using the quality in prognostic studies (QUIPS) tool. Study design, demographics, musculoskeletal region, inclusion/exclusion criteria, measurement timelines, predictor and primary outcome measures, and results were extracted. Data were synthesized qualitatively and strength of evidence was scored using the grading of recommendations, assessment, development, and evaluations (GRADE) scoring system. Nine eligible articles were located, in various musculoskeletal populations (whiplash, n = 2; widespread pain, n = 5; temporomandibular disorder, n = 2). Moderate evidence was found for 2 predictive factors of altered central pain modulation: 1) high sensory sensitivity (using genetic testing or quantitative sensory tests), and 2) psychological

  20. Working through the pain: working memory capacity and differences in processing and storage under pain.

    Science.gov (United States)

    Sanchez, Christopher A

    2011-02-01

    It has been suggested that pain perception and attention are closely linked at both a neural and a behavioural level. If pain and attention are so linked, it is reasonable to speculate that those who vary in working memory capacity (WMC) should be affected by pain differently. This study compares the performance of individuals who differ in WMC as they perform processing and memory span tasks while under mild pain and not. While processing performance under mild pain does not interact with WMC, the ability to store information for later recall does. This suggests that pain operates much like an additional processing burden, and that the ability to overcome this physical sensation is related to differences in WMC. © 2011 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business

  1. Modulation of pain-induced neuromuscular trunk responses by pain expectations: a single group study.

    Science.gov (United States)

    Tétreau, Charles; Dubois, Jean-Daniel; Piché, Mathieu; Descarreaux, Martin

    2012-10-01

    The purpose of this study was to investigate the alteration of pain-induced neuromuscular trunk responses by expectations in healthy volunteers. Twenty-three asymptomatic participants performed series of flexion-extension movements in 3 different experimental conditions: innocuous heat stimulation (control) and noxious heat stimulation associated with expectations of low or high pain intensity. These stimuli were administered by a contact thermode placed over the lumbar region (L4 and L5) to assess the modulation of neuromuscular responses and kinematics during the flexion-extension task. Surface electromyography (EMG) of lumbar erector spinae at L2 and L3 and L4 and L5 as well as lumbopelvic kinematic variables were compared across conditions. Noxious stimulation significantly altered EMG responses but only in full trunk flexion. Interestingly, this alteration was significant only for muscles where noxious stimulation was applied (L4 and L5) and not for the other segment (L2 and L3). Conversely, expectations significantly altered EMG activity at L2 and L3 but not at the segment where noxious stimulation was applied. These results confirm previous findings and indicate that experimental pain can alter neuromuscular responses during a trunk flexion-extension task. Furthermore, this study suggests that expectations can alter some of these alterations. Future studies should determine whether neuromuscular changes induced by expectations may contribute to the transition from acute to chronic low-back pain. Copyright © 2012 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

  2. Somatosensory symptoms and signs and conditioned pain modulation in chronic post-stroke shoulder pain

    NARCIS (Netherlands)

    Roosink, M.; Renzenbrink, G.J.; Buitenweg, J.R.; Dongen, R.T.M. van; Geurts, A.C.H.; IJzerman, M.J.

    2011-01-01

    Persistent shoulder pain is a common complication after stroke. Its etiology and underlying mechanisms are not well understood and treatment is generally unsatisfactory. The objective of this study was to assess the role of central sensitization and disinhibition in chronic stroke patients with

  3. Pain modulation by nitric oxide in the spinal cord.

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    Marco Aurelio M Freire

    2009-09-01

    Full Text Available Nitric oxide (NO is a versatile messenger molecule first associated with endothelial relaxing effects. In the central nervous system (CNS, NO synthesis is primarily triggered by activation of N-methyl-D-aspartate (NMDA receptors and has a Janus face, with both beneficial and harmful properties, depending on concentration and the identity of its synthetic enzyme isoform. There are three isoforms of the NO synthesizing enzyme nitric oxide synthase (NOS: neuronal (nNOS, endothelial (eNOS, and inducible nitric oxide synthase (iNOS, each one involved with specific events in the brain. In CNS, nNOS is involved with modulation of synaptic transmission through long-term potentiation in several regions, including nociceptive circuits in the spinal cord. Here, we review the role played by NO on central pain sensitization.

  4. MicroRNA modulation in complex regional pain syndrome

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    Orlova Irina A

    2011-11-01

    Full Text Available Abstract Background Aberrant expression of small noncoding RNAs called microRNAs (miRNAs is a common feature of several human diseases. The objective of the study was to identify miRNA modulation in patients with complex regional pain syndrome (CRPS a chronic pain condition resulting from dysfunction in the central and/or peripheral nervous systems. Due to a multitude of inciting pathologies, symptoms and treatment conditions, the CRPS patient population is very heterogeneous. Our goal was to identify differentially expressed miRNAs in blood and explore their utility in patient stratification. Methods We profiled miRNAs in whole blood from 41 patients with CRPS and 20 controls using TaqMan low density array cards. Since neurogenic inflammation is known to play a significant role in CRPS we measured inflammatory markers including chemokines, cytokines, and their soluble receptors in blood from the same individuals. Correlation analyses were performed for miRNAs, inflammatory markers and other parameters including disease symptoms, medication, and comorbid conditions. Results Three different groups emerged from miRNA profiling. One group was comprised of 60% of CRPS patients and contained no control subjects. miRNA profiles from the remaining patients were interspersed among control samples in the other two groups. We identified differential expression of 18 miRNAs in CRPS patients. Analysis of inflammatory markers showed that vascular endothelial growth factor (VEGF, interleukin1 receptor antagonist (IL1Ra and monocyte chemotactic protein-1 (MCP1 were significantly elevated in CRPS patients. VEGF and IL1Ra showed significant correlation with the patients reported pain levels. Analysis of the patients who were clustered according to their miRNA profile revealed correlations that were not significant in the total patient population. Correlation analysis of miRNAs detected in blood with additional parameters identified miRNAs associated with

  5. A Brief Mindfulness Meditation Training Increases Pain Threshold and Accelerates Modulation of Response to Tonic Pain in an Experimental Study.

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    Reiner, Keren; Granot, Michal; Soffer, Eliran; Lipsitz, Joshua Dan

    2016-04-01

    Research shows that mindfulness meditation (MM) affects pain perception; however, studies have yet to measure patterns of change over time. We examined effects of MM on perception of experimental heat pain using multiple psychophysical indices, including pattern of change in response to tonic painful stimuli. We also tested the potential moderating role of baseline mindfulness. Forty participants were randomly assigned to a brief MM training or control group. We assessed: a) heat pain threshold (HPT), b) temperature which induces pain at a fixed, target intensity level, and c) response pattern over time to tonic heat pain. Compared to control group, the MM group showed increased HPT and more rapid attenuation of pain intensity for tonic pain stimuli. Moderation analyses indicated that baseline mindfulness moderated effects of MM on HPT. A brief MM intervention appears to affect perception of experimental pain both by increasing pain threshold and accelerating modulation of response. Findings may help elucidate mechanisms of MM for chronic pain. © 2015 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Deficient modulation of pain by a positive emotional context in fibromyalgia patients.

    Science.gov (United States)

    Kamping, Sandra; Bomba, Isabelle C; Kanske, Philipp; Diesch, Eugen; Flor, Herta

    2013-09-01

    This study aimed to investigate the modulating effects of emotional context on pain perception in 16 patients with fibromyalgia syndrome (FMS) and 16 healthy control (HC) subjects. An infrared laser was used to apply individually adapted painful stimuli to the dorsum of the left hand. The emotional background of the painful stimuli was modulated by concurrent presentations of negative, neutral, and positive picture stimuli selected from the International Affective Picture System. As control conditions, painful stimuli and the pictures were also presented by themselves. During each of the 5 laser-picture trials, subjects received 10 painful stimuli and were asked to rate the average intensity and unpleasantness of the experienced pain. Functional magnetic resonance images were obtained, using a T2(∗) sensitive echo planar sequence. HC subjects showed a linear increase in pain intensity and unpleasantness ratings when painful stimuli were presented during positive, neutral, and negative pictures. In contrast, FMS patients showed a quadratic trend for pain intensity ratings indicating a lack of pain reduction by the positive pictures. In addition, the FMS patients showed less activation in secondary somatosensory cortex, insula, orbitofrontal cortex, and anterior cingulate cortex during the positive picture pain trials. Our results suggest that fibromyalgia patients are less efficient in modulating pain by positive affect and may benefit less from appetitive events than healthy control subjects. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  7. Cerebral responses and role of the prefrontal cortex in conditioned pain modulation: an fMRI study in healthy subjects

    Science.gov (United States)

    Bogdanov, Volodymyr B.; Viganò, Alessandro; Noirhomme, Quentin; Bogdanova, Olena V.; Guy, Nathalie; Laureys, Steven; Renshaw, Perry F.; Dallel, Radhouane; Phillips, Christophe; Schoenen, Jean

    2017-01-01

    The mechanisms underlying conditioned pain modulation (CPM) are multifaceted. We searched for a link between individual differences in prefrontal cortex activity during multi-trial heterotopic noxious cold conditioning and modulation of the cerebral response to phasic heat pain. In 24 healthy female subjects, we conditioned laser heat stimuli to the left hand by applying alternatively ice-cold or lukewarm compresses to the right foot. We compared pain ratings with cerebral fMRI BOLD responses. We also analyzed the relation between CPM and BOLD changes produced by the heterotopic cold conditioning itself, as well as the impact of anxiety and habituation of cold-pain ratings. Specific cerebral activation was identified in precuneus and left posterior insula/SII, respectively, during early and sustained phases of cold application. During cold conditioning, laser pain decreased (n = 7), increased (n = 10) or stayed unchanged (n = 7). At the individual level, the psychophysical effect was directly proportional to the cold-induced modulation of the laser-induced BOLD response in left posterior insula/SII. The latter correlated with the BOLD response recorded 80 s earlier during the initial 10-s phase of cold application in anterior cingulate, orbitofrontal and lateral prefrontal cortices. High anxiety and habituation of cold pain were associated with greater laser heat-induced pain during heterotopic cold stimulation. The habituation was also linked to the early cold-induced orbitofrontal responses. We conclude that individual differences in conditioned pain modulation are related to different levels of prefrontal cortical activation by the early part of the conditioning stimulus, possibly due to different levels in trait anxiety. PMID:25461267

  8. Dysfunctional Pain Modulation in Torture Survivors: The Mediating Effect of PTSD.

    Science.gov (United States)

    Defrin, Ruth; Lahav, Yael; Solomon, Zahava

    2017-01-01

    Trauma survivors, and particularly torture survivors, suffer from high rates of chronic pain and posttraumatic stress disorder (PTSD) for years afterward, along with alterations in the function of the pain system. On the basis of longitudinal data on PTSD symptomatology, we tested whether exposure to torture, PTSD or PTSD trajectories accounted for chronic pain and altered pain perception. Participants were 59 torture survivors and 44 age-matched healthy control subjects. Chronic pain was characterized. Pain threshold, pain tolerance, conditioned pain modulation (CPM), and temporal summation of pain were measured. Three PTSD trajectories were identified among torture survivors; chronic, delayed, and resilient. Lack of CPM and more intense chronic pain was found among the chronic and delayed groups compared with the resilient and healthy control groups. Temporal summation of pain was strongest among the chronic group. PTSD trajectories mediated the relationship between torture and CPM. It appears that the duration and severity of posttraumatic distress, rather than the exposure to trauma, are crucial factors that mediate the association between trauma and chronic pain. Because PTSD and its resultant distress are measurable, their evaluation seems particularly important in the management of pain among trauma survivors. The results may be generalized to other instances in which chronic pain persists after traumatic events. This article presents the mediation effect of PTSD trajectory on pain modulation among trauma survivors suggesting that it is the duration and severity of PTSD/distress, rather than the exposure to trauma per se, that influence the perception and modulation of pain. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  9. Rostral Agranular Insular Cortex Lesion with Motor Cortex Stimulation Enhances Pain Modulation Effect on Neuropathic Pain Model

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    Hyun Ho Jung

    2016-01-01

    Full Text Available It is well known that the insular cortex is involved in the processing of painful input. The aim of this study was to evaluate the pain modulation role of the insular cortex during motor cortex stimulation (MCS. After inducing neuropathic pain (NP rat models by the spared nerve injury method, we made a lesion on the rostral agranular insular cortex (RAIC unilaterally and compared behaviorally determined pain threshold and latency in 2 groups: Group A (NP + MCS; n=7 and Group B (NP + RAIC lesion + MCS; n=7. Also, we simultaneously recorded neuronal activity (NP; n=9 in the thalamus of the ventral posterolateral nucleus and RAIC to evaluate electrophysiological changes from MCS. The pain threshold and tolerance latency increased in Group A with “MCS on” and in Group B with or without “MCS on.” Moreover, its increase in Group B with “MCS on” was more than that of Group B without MCS or of Group A, suggesting that MCS and RAIC lesioning are involved in pain modulation. Compared with the “MCS off” condition, the “MCS on” induced significant threshold changes in an electrophysiological study. Our data suggest that the RAIC has its own pain modulation effect, which is influenced by MCS.

  10. Topiramate modulates trigeminal pain processing in thalamo-cortical networks in humans after single dose administration.

    Science.gov (United States)

    Hebestreit, Julia M; May, Arne

    2017-01-01

    Migraine is the sixth most common cause of disability in the world. Preventive migraine treatment is used to reduce frequency, severity and duration of attacks and therefore lightens the burden on the patients' quality of life and reduces disability. Topiramate is one of the preventive migraine treatments of proven efficacy. The mechanism of action underlying the preventive effect of topiramate in migraine remains largely unknown. Using functional magnetic resonance imaging (fMRI) we examined the central effects of a single dose of topiramate (100mg) on trigeminal pain in humans, compared to placebo (mannitol). In this prospective, within subject, randomized, placebo-controlled and double-blind study, 23 healthy participants received a standardized nociceptive trigeminal stimulation and control stimuli whilst being in the scanner. No differences in the subjective intensity ratings of the painful stimuli were observed between topiramate and placebo sessions. In contrast, topiramate significantly decreased the activity in the thalamus and other pain processing areas. Additionally, topiramate increased functional coupling between the thalamus and several brain regions such as the bilateral precuneus, posterior cingulate cortex and secondary somatosensory cortex. These data suggest that topiramate exhibits modulating effects on nociceptive processing in thalamo-cortical networks during trigeminal pain and that the preventive effect of topiramate on frequent migraine is probably mediated by an effect on thalamo-cortical networks.

  11. Potential Mechanisms Underlying Centralized Pain and Emerging Therapeutic Interventions

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    Olivia C. Eller-Smith

    2018-02-01

    Full Text Available Centralized pain syndromes are associated with changes within the central nervous system that amplify peripheral input and/or generate the perception of pain in the absence of a noxious stimulus. Examples of idiopathic functional disorders that are often categorized as centralized pain syndromes include fibromyalgia, chronic pelvic pain syndromes, migraine, and temporomandibular disorder. Patients often suffer from widespread pain, associated with more than one specific syndrome, and report fatigue, mood and sleep disturbances, and poor quality of life. The high degree of symptom comorbidity and a lack of definitive underlying etiology make these syndromes notoriously difficult to treat. The main purpose of this review article is to discuss potential mechanisms of centrally-driven pain amplification and how they may contribute to increased comorbidity, poorer pain outcomes, and decreased quality of life in patients diagnosed with centralized pain syndromes, as well as discuss emerging non-pharmacological therapies that improve symptomology associated with these syndromes. Abnormal regulation and output of the hypothalamic-pituitary-adrenal (HPA axis is commonly associated with centralized pain disorders. The HPA axis is the primary stress response system and its activation results in downstream production of cortisol and a dampening of the immune response. Patients with centralized pain syndromes often present with hyper- or hypocortisolism and evidence of altered downstream signaling from the HPA axis including increased Mast cell (MC infiltration and activation, which can lead to sensitization of nearby nociceptive afferents. Increased peripheral input via nociceptor activation can lead to “hyperalgesic priming” and/or “wind-up” and eventually to central sensitization through long term potentiation in the central nervous system. Other evidence of central modifications has been observed through brain imaging studies of functional

  12. Modulation of vagal tone enhances gastroduodenal motility and reduces somatic pain sensitivity

    DEFF Research Database (Denmark)

    Frøkjaer, J B; Bergmann, S; Brock, C

    2016-01-01

    algometry, conditioned pain modulation using a cold pressor test and a liquid meal ultrasonographic gastroduodenal motility test were performed. KEY RESULTS: Cardiac vagal tone increased during active treatment with t-VNS and DSB compared to sham (p = 0.009). In comparison to sham, thresholds to bone pain...... increased (p = 0.001), frequency of antral contractions increased (p = 0.004) and gastroduodenal motility index increased (p = 0.016) with active treatment. However, no effect on muscle pain thresholds and conditioned pain modulation was seen. CONCLUSIONS & INFERENCES: This experimental study suggests...

  13. Beyond weakness: Characterization of pain, sensory profile and conditioned pain modulation in patients with motor neuron disease: A controlled study.

    Science.gov (United States)

    Lopes, L C G; Galhardoni, R; Silva, V; Jorge, F M H; Yeng, L T; Callegaro, D; Chadi, G; Teixeira, M J; Ciampi de Andrade, D

    2018-01-01

    Motor neuron diseases (MND) represent a group of disorders that evolve with inexorable muscle weakness and medical management is based on symptom control. However, deeper characterization of non-motor symptoms in these patients have been rarely reported. This cross-sectional study aimed to describe non-motor symptoms in MND and their impact on quality of life and functional status, with a focus on pain and sensory changes. Eighty patients (31 females, 55.7 ± 12.9 years old) with MND underwent a neurological examination, pain, mood, catastrophizing and psychophysics assessments [quantitative sensory testing (QST) and conditioned pain modulation (CPM)], and were compared to sex- and age-matched healthy controls (HC). Chronic pain was present in 46% of patients (VAS =5.18 ± 2.0). Pain of musculoskeletal origin occurred in 40.5% and was mainly located in the head/neck (51%) and lower back (35%). Neuropathic pain was not present in this sample. Compared to HC, MND patients had a lower cold detection threshold (p catastrophism, and spasticity scores were inversely correlated with CPM (ρ = -0.30, p = 0.026). Pain is frequently reported by patients with MNDs. Somatosensory and CPM changes exist in MNDs and may be related to the neurodegenerative nature of the disease. Further studies should investigate the most appropriate treatment strategies for these patients. We report a comprehensive evaluation of pain and sensory abnormalities in motor neuron disease (MND) patients. We assessed the different pain syndromes present in MND with validated tools, and described the QST and conditioned pain modulation profiles in a controlled design. © 2017 European Pain Federation - EFIC®.

  14. The Role of the Brain's Endocannabinoid System in Pain and Its Modulation by Stress.

    Science.gov (United States)

    Corcoran, Louise; Roche, Michelle; Finn, David P

    2015-01-01

    Stress has a complex, bidirectional modulatory influence on pain. Stress may either reduce (stress-induced analgesia) or exacerbate (stress-induced hyperalgesia) pain depending on the nature, duration, and intensity of the stressor. The endogenous cannabinoid (endocannabinoid) system is present throughout the neuroanatomical pathways that mediate and modulate responses to painful stimuli. The specific role of the endocannabinoid system in the brain in pain and the modulation of pain by stress is reviewed herein. We first provide a brief overview of the endocannabinoid system, followed by a review of the evidence that the brain's endocannabinoid system modulates pain. We provide a comprehensive evaluation of the role of the endocannabinoid system supraspinally, and particularly in the rostral ventromedial medulla, periaqueductal gray, amygdala, and prefrontal cortex, in pain, stress-induced analgesia, and stress-induced hyperalgesia. Increased understanding of endocannabinoid-mediated regulation of pain and its modulation by stress will inform the development of novel therapeutic approaches for pain and its comorbidity with stress-related disorders. © 2015 Elsevier Inc. All rights reserved.

  15. Physical activity, sustained sedentary behavior, and pain modulation in women with fibromyalgia.

    Science.gov (United States)

    Ellingson, Laura D; Shields, Morgan R; Stegner, Aaron J; Cook, Dane B

    2012-02-01

    Fibromyalgia (FM) has been conceptualized as a disorder of the central nervous system, characterized by augmented sensory processing and an inability to effectively modulate pain. We previously reported that physical activity is related to brain processing of pain, providing evidence for a potential mechanism of pain management. The purpose of this study was to extend our work by manipulating pain modulation and determining relationships to both physical activity and sustained sedentary behavior. Eleven women with FM completed accelerometer measures of physical activity and underwent functional magnetic resonance imaging of painful heat, administered alone and during distracting cognitive tasks. Results showed that physical activity was significantly (P sedentary time, significant negative relationships were observed in areas involved in both pain modulation and the sensory-discriminative aspects of pain including the DLPFC, thalamus, and superior frontal and pre- and post-central gyri. These results suggest that physical activity and sedentary behaviors are related to central nervous system regulation of pain in FM. Our results support a promising benefit of physical activity and highlight the potentially deleterious effects of sustained sedentary behavior for pain regulation in FM. Studies aimed at increasing physical activity or reducing sedentary behavior and determining the impact of these on pain regulation are warranted. Published by Elsevier Inc.

  16. Activated microglia in the spinal cord underlies diabetic neuropathic pain.

    Science.gov (United States)

    Wang, Dongmei; Couture, Réjean; Hong, Yanguo

    2014-04-05

    Diabetes mellitus is an increasingly common chronic medical condition. Approximately 30% of diabetic patients develop neuropathic pain, manifested as spontaneous pain, hyperalgesia and allodynia. Hyperglycemia induces metabolic changes in peripheral tissues and enhances oxidative stress in nerve fibers. The damages and subsequent reactive inflammation affect structural properties of Schwann cells and axons leading to the release of neuropoietic mediators, such as pro-inflammatory cytokines and pro-nociceptive mediators. Therefore, diabetic neuropathic pain (DNP) shares some histological features and underlying mechanisms with traumatic neuropathy. DNP displays, however, other distinct features; for instance, sensory input to the spinal cord decreases rather than increasing in diabetic patients. Consequently, development of central sensitization in DNP involves mechanisms that are distinct from traumatic neuropathic pain. In DNP, the contribution of spinal cord microglia activation to central sensitization and pain processes is emerging as a new concept. Besides inflammation in the periphery, hyperglycemia and the resulting production of reactive oxygen species affect the local microenvironment in the spinal cord. All these alterations could trigger resting and sessile microglia to the activated phenotype. In turn, microglia synthesize and release pro-inflammatory cytokines and neuroactive molecules capable of inducing hyperactivity of spinal nociceptive neurons. Hence, it is imperative to elucidate glial mechanisms underlying DNP for the development of effective therapeutic agents. The present review highlights the recent developments regarding the contribution of spinal microglia as compelling target for the treatment of DNP. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Altered central sensitization and pain modulation in the CNS in chronic joint pain

    DEFF Research Database (Denmark)

    Arendt-Nielsen, Lars; Skou, Søren Thorgaard; Nielsen, Thomas Arendt

    2015-01-01

    and central pain mechanisms are not fully understood, and safe and efficient analgesic drugs are not available. The pain associated with joint pain is highly individual, and features from radiological imaging have not demonstrated robust associations with the pain manifestations. In recent years, a variety...

  18. Muscle pain induced by static contraction in rats is modulated by peripheral inflammatory mechanisms.

    Science.gov (United States)

    Santos, Diogo Francisco da Silva Dos; Melo Aquino, Bruna de; Jorge, Carolina Ocanha; Azambuja, Graciana de; Schiavuzzo, Jalile Garcia; Krimon, Suzy; Neves, Juliana Dos Santos; Parada, Carlos Amilcar; Oliveira-Fusaro, Maria Claudia Gonçalves

    2017-09-01

    Muscle pain is an important health issue and frequently related to static force exertion. The aim of this study is to evaluate whether peripheral inflammatory mechanisms are involved with static contraction-induced muscle pain in rats. To this end, we developed a model of muscle pain induced by static contraction performed by applying electrical pulses through electrodes inserted into muscle. We also evaluated the involvement of neutrophil migration, bradykinin, sympathetic amines and prostanoids. A single session of sustained static contraction of gastrocnemius muscle induced acute mechanical muscle hyperalgesia without affecting locomotor activity and with no evidence of structural damage in muscle tissue. Static contraction increased levels of creatine kinase but not lactate dehydrogenase, and induced neutrophil migration. Dexamethasone (glucocorticoid anti-inflammatory agent), DALBK (bradykinin B1 antagonist), Atenolol (β1 adrenoceptor antagonist), ICI 118,551 (β2 adrenoceptor antagonist), indomethacin (cyclooxygenase inhibitor), and fucoidan (non-specific selectin inhibitor) all reduced static contraction-induced muscle hyperalgesia; however, the bradykinin B2 antagonist, bradyzide, did not have an effect on static contraction-induced muscle hyperalgesia. Furthermore, an increased hyperalgesic response was observed when the selective bradykinin B1 agonist des-Arg 9 -bradykinin was injected into the previously stimulated muscle. Together, these findings demonstrate that static contraction induced mechanical muscle hyperalgesia in gastrocnemius muscle of rats is modulated through peripheral inflammatory mechanisms that are dependent on neutrophil migration, bradykinin, sympathetic amines and prostanoids. Considering the clinical relevance of muscle pain, we propose the present model of static contraction-induced mechanical muscle hyperalgesia as a useful tool for the study of mechanisms underlying static contraction-induced muscle pain. Copyright © 2017 IBRO

  19. Theoretical Study of Semiconductor Laser under Modulation

    Science.gov (United States)

    Boukari, O.; Hassine, L.; Dherbecourt, P.; Latry, O.; Ketata, M.; Bouchriha, H.

    2007-09-01

    In this paper we present a description of the chirp induced in a direct modulated DFB laser. Our study is follows two different approaches. The first approach is based on a resolution of the rate equations of laser; the second, on a simulation of a heterodyne system with the Optisystem software. This study enables us to visualize the chirp in the RF field. We also characterize it according to the injection current i(t) parameters, such as the amplitude and the frequency of the modulation. The aim of our study is to choose the appropriate values of these parameters, in order to use the direct modulated DFB laser as an optical tunable source for Coherent Optical Frequency Domain Reflectometry technique (C-OFDR). We demonstrate that the optical frequency of these lasers can be controlled via the injection current i(t) and it can be linearly swept (chirped) over some tens of gigahertz.

  20. Rab7-a novel redox target that modulates inflammatory pain processing.

    Science.gov (United States)

    Kallenborn-Gerhardt, Wiebke; Möser, Christine V; Lorenz, Jana E; Steger, Mirco; Heidler, Juliana; Scheving, Reynir; Petersen, Jonas; Kennel, Lea; Flauaus, Cathrin; Lu, Ruirui; Edinger, Aimee L; Tegeder, Irmgard; Geisslinger, Gerd; Heide, Heinrich; Wittig, Ilka; Schmidtko, Achim

    2017-07-01

    Chronic pain is accompanied by production of reactive oxygen species (ROS) in various cells that are important for nociceptive processing. Recent data indicate that ROS can trigger specific redox-dependent signaling processes, but the molecular targets of ROS signaling in the nociceptive system remain largely elusive. Here, we performed a proteome screen for pain-dependent redox regulation using an OxICAT approach, thereby identifying the small GTPase Rab7 as a redox-modified target during inflammatory pain in mice. Prevention of Rab7 oxidation by replacement of the redox-sensing thiols modulates its GTPase activity. Immunofluorescence studies revealed Rab7 expression to be enriched in central terminals of sensory neurons. Knockout mice lacking Rab7 in sensory neurons showed normal responses to noxious thermal and mechanical stimuli; however, their pain behavior during inflammatory pain and in response to ROS donors was reduced. The data suggest that redox-dependent changes in Rab7 activity modulate inflammatory pain sensitivity.

  1. Enhanced Brain Responses to Pain-Related Words in Chronic Back Pain Patients and Their Modulation by Current Pain

    Directory of Open Access Journals (Sweden)

    Alexander Ritter

    2016-08-01

    Full Text Available Previous functional magnetic resonance imaging (fMRI studies in healthy controls (HC and pain-free migraine patients found activations to pain-related words in brain regions known to be activated while subjects experience pain. The aim of the present study was to identify neural activations induced by pain-related words in a sample of chronic back pain (CBP patients experiencing current chronic pain compared to HC. In particular, we were interested in how current pain influences brain activations induced by pain-related adjectives. Subjects viewed pain-related, negative, positive, and neutral words; subjects were asked to generate mental images related to these words during fMRI scanning. Brain activation was compared between CBP patients and HC in response to the different word categories and examined in relation to current pain in CBP patients. Pain-related words vs. neutral words activated a network of brain regions including cingulate cortex and insula in subjects and patients. There was stronger activation in medial and dorsolateral prefrontal cortex (DLPFC and anterior midcingulate cortex in CPB patients than in HC. The magnitude of activation for pain-related vs. negative words showed a negative linear relationship to CBP patients’ current pain. Our findings confirm earlier observations showing that pain-related words activate brain networks similar to noxious stimulation. Importantly, CBP patients show even stronger activation of these structures while merely processing pain-related words. Current pain directly influences on this activation.

  2. Enhanced Brain Responses to Pain-Related Words in Chronic Back Pain Patients and Their Modulation by Current Pain.

    Science.gov (United States)

    Ritter, Alexander; Franz, Marcel; Puta, Christian; Dietrich, Caroline; Miltner, Wolfgang H R; Weiss, Thomas

    2016-08-10

    Previous functional magnetic resonance imaging (fMRI) studies in healthy controls (HC) and pain-free migraine patients found activations to pain-related words in brain regions known to be activated while subjects experience pain. The aim of the present study was to identify neural activations induced by pain-related words in a sample of chronic back pain (CBP) patients experiencing current chronic pain compared to HC. In particular, we were interested in how current pain influences brain activations induced by pain-related adjectives. Subjects viewed pain-related, negative, positive, and neutral words; subjects were asked to generate mental images related to these words during fMRI scanning. Brain activation was compared between CBP patients and HC in response to the different word categories and examined in relation to current pain in CBP patients. Pain-related words vs. neutral words activated a network of brain regions including cingulate cortex and insula in subjects and patients. There was stronger activation in medial and dorsolateral prefrontal cortex (DLPFC) and anterior midcingulate cortex in CPB patients than in HC. The magnitude of activation for pain-related vs. negative words showed a negative linear relationship to CBP patients' current pain. Our findings confirm earlier observations showing that pain-related words activate brain networks similar to noxious stimulation. Importantly, CBP patients show even stronger activation of these structures while merely processing pain-related words. Current pain directly influences on this activation.

  3. Evidence for a key role of steroids in the modulation of pain.

    Science.gov (United States)

    Mensah-Nyagan, Ayikoe G; Meyer, Laurence; Schaeffer, Véronique; Kibaly, Cherkaouia; Patte-Mensah, Christine

    2009-12-01

    Neurotransmitters such as glutamate, substance P, serotonin and gamma-aminobutyric acid pivotally control pain mechanisms. It is also well known that inflammatory and/or neuropathic pain may depend on the action of diverse cytokines and other molecules including eicosanoids, endorphins, calcitonin-gene related peptide, free radicals and transcription factors. Because steroids control the development, activities and plasticity of the nervous system, these compounds are of particular interest in the modulation of pain. The paper discusses various data supporting the existence of key regulatory effects of steroids in the control of pain. In particular, we analyzed three categories of observations which historically contributed to demonstrate that endogenous and synthetic steroids play a crucial role in the regulation of neurobiological processes involved in pain sensation. The first series of data, which present the chemical characteristics enabling steroids to act on several tissues, also summarize pertinent results supporting the modulation of pain sensation by steroidal compounds. The second category of data evokes psychosocial, fundamental and clinical results suggesting the existence of sex steroid-based differences in pain perception. Finally, we discuss recent evidence showing the endogenous production of neurosteroids and their effects in the spinal cord which crucially controls pain transmission. Taken together, the data reviewed herein suggest that future investigations aiming to develop effective steroid-based strategies against chronic pain must integrate in a complementary manner anti-inflammatory properties of steroids, sex steroid-induced dimorphism in pain perception and regulatory effects exerted by endogenous neurosteroids in pain neural circuits.

  4. A review of the role of orexin system in pain modulation.

    Science.gov (United States)

    Razavi, Bibi Marjan; Hosseinzadeh, Hossein

    2017-06-01

    The roles of orexinergic system (orexin-A, orexin-B) and their receptors (orexin receptor type-1, orexin receptor type-2) in various physiological processes such as arousal, reward seeking behavior, energy homeostasis, sensory modulation, stress processing, cognition, endocrine functions, visceral functions and pain modulation have been established. This review summarizes the studies investigating orexin antinociceptive effects and their cellular mechanisms in various types of pain including neuropathic pain, migraine and cluster headache, visceral and orofacial pains. Moreover, the role of orexins in stress induced analgesia and on the development of morphine analgesic tolerance has been discussed. The antinociceptive effects of orexins have been shown in several pain models including thermal, mechanical and chemical induced nociception. Orexins modulate pain perception at both spinal and supraspinal levels. The periaqueductal gray (PAG) is one important supraspinal sites of orexin pain modulation. A possible involvement of endocannabinoids in supraspinal orexin-induced analgesia has been proposed. This review suggests a potential role of orexins in the management of pain. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Endogenous Pain Modulation: Association with Resting Heart Rate Variability and Negative Affectivity.

    Science.gov (United States)

    Van Den Houte, Maaike; Van Oudenhove, Lukas; Bogaerts, Katleen; Van Diest, Ilse; Van den Bergh, Omer

    2017-07-21

    Several chronic pain syndromes are characterized by deficient endogenous pain modulation as well as elevated negative affectivity and reduced resting heart rate variability. In order to elucidate the relationships between these characteristics, we investigated whether negative affectivity and heart rate variability are associated with endogenous pain modulation in a healthy population. An offset analgesia paradigm with noxious thermal stimulation calibrated to the individual's pain threshold was used to measure endogenous pain modulation magnitude in 63 healthy individuals. Pain ratings during constant noxious heat stimulation to the arm (15 seconds) were compared with ratings during noxious stimulation comprising a 1 °C rise and return of temperature to the initial level (offset trials, 15 seconds). Offset analgesia was defined as the reduction in pain following the 1 °C decrease relative to pain at the same time point during continuous heat stimulation. Evidence for an offset analgesia effect could only be found when noxious stimulation intensity (and, hence, the individual's pain threshold) was intermediate (46 °C or 47 °C). Offset analgesia magnitude was also moderated by resting heart rate variability: a small but significant offset effect was found in participants with high but not low heart rate variability. Negative affectivity was not related to offset analgesia magnitude. These results indicate that resting heart rate variability (HRV) is related to endogenous pain modulation (EPM) in a healthy population. Future research should focus on clarifying the causal relationship between HRV and EPM and chronic pain by using longitudinal study designs. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  6. Pain and sensory detection threshold response to acupuncture is modulated by coping strategy and acupuncture sensation.

    Science.gov (United States)

    Lee, Jeungchan; Napadow, Vitaly; Park, Kyungmo

    2014-09-01

    Acupuncture has been shown to reduce pain, and acupuncture-induced sensation may be important for this analgesia. In addition, cognitive coping strategies can influence sensory perception. However, the role of coping strategy on acupuncture modulation of pain and sensory thresholds, and the association between acupuncture sensation and these modulatory effects, is currently unknown. Electroacupuncture (EA) was applied at acupoints ST36 and GB39 of 61 healthy adults. Different coping conditions were experimentally designed to form an active coping strategy group (AC group), who thought they could control EA stimulation intensity, and a passive coping strategy group (PC group), who did not think they had such control. Importantly, neither group was actually able to control EA stimulus intensity. Quantitative sensory testing was performed before and after EA, and consisted of vibration (VDT), mechanical (MDT), warm (WDT), and cold (CDT) detection thresholds, and pressure (PPT), mechanical (MPT), heat (HPT) and cold (CPT) pain thresholds. Autonomic measures (e.g. skin conductance response, SCR) were also acquired to quantify physiological response to EA under different coping conditions. Subjects also reported the intensity of any acupuncture-induced sensations. Coping strategy was induced with successful blinding in 58% of AC subjects. Compared to PC, AC showed greater SCR to EA. Under AC, EA reduced PPT and CPT. In the AC group, improved pain and sensory thresholds were correlated with acupuncture sensation (VDTchange vs. MI: r=0.58, CDTchange vs. tingling: r=0.53, CPTchange vs. tingling; r=0.55, CPTchange vs. dull; r=0.55). However, in the PC group, improved sensory thresholds were negatively correlated with acupuncture sensation (CDTchange vs. intensity sensitization: r=-0.52, WDTchange vs. fullness: r=-0.57). Our novel approach was able to successfully induce AC and PC strategies to EA stimulation. The interaction between psychological coping strategy and

  7. Spinal cord stimulation and modulation of neuropathic pain

    NARCIS (Netherlands)

    de Vos, Cecilia Cecilia Clementine

    2013-01-01

    This thesis reports on the opportunities of several new applications of spinal cord stimulation (SCS) for the treatment of neuropathic pain. Our pilot study and consecutively performed international randomised controlled trial on effects of SCS in patients with painful diabetic neuropathy showed

  8. Exposure to Virtual Social Stimuli Modulates Subjective Pain Reports

    Directory of Open Access Journals (Sweden)

    Jacob M Vigil

    2014-01-01

    Full Text Available BACKGROUND: Contextual factors, including the gender of researchers, influence experimental and patient pain reports. It is currently not known how social stimuli influence pain percepts, nor which types of sensory modalities of communication, such as auditory, visual or olfactory cues associated with person perception and gender processing, produce these effects.

  9. Modulation of oral heat and cold pain by irritant chemicals.

    Science.gov (United States)

    Albin, Kelly C; Carstens, Mirela Iodi; Carstens, E

    2008-01-01

    Common food irritants elicit oral heat or cool sensations via actions at thermosensitive transient receptor potential (TRP) channels. We used a half-tongue, 2-alternative forced-choice procedure coupled with bilateral pain intensity ratings to investigate irritant effects on heat and cold pain. The method was validated in a bilateral thermal difference detection task. Capsaicin, mustard oil, and cinnamaldehyde enhanced lingual heat pain elicited by a 49 degrees C stimulus. Mustard oil and cinnamaldehyde weakly enhanced lingual cold pain (9.5 degrees C), whereas capsaicin had no effect. Menthol significantly enhanced cold pain and weakly reduced heat pain. To address if capsaicin's effect was due to summation of perceptually similar thermal and chemical sensations, one-half of the tongue was desensitized by application of capsaicin. Upon reapplication, capsaicin elicited little or no irritant sensation yet still significantly enhanced heat pain on the capsaicin-treated side, ruling out summation. In a third experiment, capsaicin significantly enhanced pain ratings to graded heat stimuli (47 degrees C to 50 degrees C) resulting in an upward shift of the stimulus-response function. Menthol may induce cold hyperalgesia via enhanced thermal gating of TRPM8 in peripheral fibers. Capsaicin, mustard oil, and cinnamaldehyde may induce heat hyperalgesia via enhanced thermal gating of TRPV1 that is coexpressed with TRPA1 in peripheral nociceptors.

  10. Temporomandibular disorders and painful comorbidities: clinical association and underlying mechanisms.

    Science.gov (United States)

    Costa, Yuri Martins; Conti, Paulo César Rodrigues; de Faria, Flavio Augusto Cardoso; Bonjardim, Leonardo Rigoldi

    2017-03-01

    The association between temporomandibular disorders (TMDs) and headaches, cervical spine dysfunction, and fibromyalgia is not artefactual. The aim of this review is to describe the comorbid relationship between TMD and these three major painful conditions and to discuss the clinical implications and the underlying pain mechanisms involved in these relationships. Common neuronal pathways and central sensitization processes are acknowledged as the main factors for the association between TMD and primary headaches, although the establishment of cause-effect mechanisms requires further clarification and characterization. The biomechanical aspects are not the main factors involved in the comorbid relationship between TMD and cervical spine dysfunction, which can be better explained by the neuronal convergence of the trigeminal and cervical spine sensory pathways as well as by central sensitization processes. The association between TMD and fibromyalgia also has supporting evidence in the literature, and the proposed main mechanism underlying this relationship is the impairment of the descending pain inhibitory system. In this particular scenario, a cause-effect relationship is more likely to occur in one direction, that is, fibromyalgia as a risk factor for TMD. Therefore, clinical awareness of the association between TMD and painful comorbidities and the support of multidisciplinary approaches are required to recognize these related conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Brain Mechanisms Supporting Modulation of Pain by Mindfulness Meditation

    Science.gov (United States)

    Zeidan, F.; Martucci, K.T.; Kraft, R.A.; Gordon, N.S.; McHaffie, J.G.; Coghill, R.C.

    2011-01-01

    The subjective experience of one’s environment is constructed by interactions among sensory, cognitive, and affective processes. For centuries, meditation has been thought to influence such processes by enabling a non-evaluative representation of sensory events. To better understand how meditation influences the sensory experience, we employed arterial spin labeling (ASL) functional magnetic resonance imaging to assess the neural mechanisms by which mindfulness meditation influences pain in healthy human participants. After four-days of mindfulness meditation training, meditating in the presence of noxious stimulation significantly reduced pain-unpleasantness by 57% and pain-intensity ratings by 40% when compared to rest. A two factor repeated measures analysis of variance was used to identify interactions between meditation and pain-related brain activation. Meditation reduced pain-related activation of the contra lateral primary somatosensory cortex. Multiple regression analysis was used to identify brain regions associated with individual differences in the magnitude of meditation-related pain reductions. Meditation-induced reductions in pain intensity ratings were associated with increased activity in the anterior cingulate cortex and anterior insula, areas involved in the cognitive regulation of nociceptive processing. Reductions in pain unpleasantness ratings were associated with orbitofrontal cortex activation, an area implicated in reframing the contextual evaluation of sensory events. Moreover, reductions in pain unpleasantness also were associated with thalamic deactivation, which may reflect a limbic gating mechanism involved in modifying interactions between afferent in put and executive-order brain areas. Taken together, these data indicate that meditation engages multiple brain mechanisms that alter the construction of the subjectively available pain experience from afferent information. PMID:21471390

  12. Witnessing hateful people in pain modulates brain activity in regions associated with physical pain and reward.

    Directory of Open Access Journals (Sweden)

    Glenn Ryan Fox

    2013-10-01

    Full Text Available How does witnessing a hateful person in pain compare to witnessing a likable person in pain? The current study compared the brain bases for how we perceive likable people in pain with those of viewing hateful people in pain. While social bonds are built through sharing the plight and pain of others in the name of empathy, viewing a hateful person in pain also has many potential ramifications. In this functional Magnetic Resonance Imaging (fMRI study, Caucasian Jewish male participants viewed videos of (1 disliked, hateful, anti-Semitic individuals, and (2 liked, non-hateful, tolerant individuals in pain. The results showed that, compared with viewing liked people, viewing hateful people in pain elicited increased responses in regions associated with observation of physical pain (the insular cortex, the anterior cingulate cortex, and the somatosensory cortex, reward processing (the striatum, and frontal regions associated with emotion regulation. Functional connectivity analyses revealed connections between seed regions in the left anterior cingulate cortex and right insular cortex with reward regions, the amygdala, and frontal regions associated with emotion regulation. These data indicate that regions of the brain active while viewing someone in pain may be more active in response to the danger or threat posed by witnessing the pain of a hateful individual more so than the desire to empathize with a likable person’s pain.

  13. The Social Modulation of Pain: Others as Predictive Signals of Salience – a Systematic Review

    Science.gov (United States)

    Krahé, Charlotte; Springer, Anne; Weinman, John A.; Fotopoulou, Aikaterini

    2013-01-01

    Several studies in cognitive neuroscience have investigated the cognitive and affective modulation of pain. By contrast, fewer studies have focused on the social modulation of pain, despite a plethora of relevant clinical findings. Here we present the first review of experimental studies addressing how interpersonal factors, such as the presence, behavior, and spatial proximity of an observer, modulate pain. Based on a systematic literature search, we identified 26 studies on experimentally induced pain that manipulated different interpersonal variables and measured behavioral, physiological, and neural pain-related responses. We observed that the modulation of pain by interpersonal factors depended on (1) the degree to which the social partners were active or were perceived by the participants to possess possibility for action; (2) the degree to which participants could perceive the specific intentions of the social partners; (3) the type of pre-existing relationship between the social partner and the person in pain, and lastly, (4) individual differences in relating to others and coping styles. Based on these findings, we propose that the modulation of pain by social factors can be fruitfully understood in relation to a recent predictive coding model, the free energy framework, particularly as applied to interoception and social cognition. Specifically, we argue that interpersonal interactions during pain may function as social, predictive signals of contextual threat or safety and as such influence the salience of noxious stimuli. The perception of such interpersonal interactions may in turn depend on (a) prior beliefs about interpersonal relating and (b) the certainty or precision by which an interpersonal interaction may predict environmental threat or safety. PMID:23888136

  14. The social modulation of pain: Others as predictive signals of salience – A systematic review

    Directory of Open Access Journals (Sweden)

    Charlotte eKrahé

    2013-07-01

    Full Text Available Several studies in cognitive neuroscience have investigated the cognitive and affective modulation of pain. By contrast, fewer studies have focused on the social modulation of pain, despite a plethora of relevant clinical findings. Here we present the first review of experimental studies addressing how interpersonal factors, such as the presence, behaviour and spatial proximity of an observer, modulate pain. Based on a systematic literature search we identified twenty-six studies on experimentally-induced pain that manipulated different interpersonal variables and measured behavioural, physiological and neural pain-related responses. We observed that the modulation of pain by interpersonal factors depended on (1 the degree to which the social partners were active or were perceived by the participants to possess possibility for action; (2 the degree to which participants could perceive the specific intentions of the social partners; (3 the type of pre-existing relationship between the social partner and the person in pain, and lastly, (4 individual differences in relating to others and coping styles. Based on these findings, we propose that the modulation of pain by social factors can be fruitfully understood in relation to a recent predictive coding model, the free energy framework, particularly as applied to interoception and social cognition. Specifically, we argue that interpersonal interactions during pain may function as social, predictive signals of contextual threat or safety and as such influence the salience of noxious stimuli. The perception of such interpersonal interactions may in turn depend on (a prior beliefs about interpersonal relating and (b the certainty or precision by which an interpersonal interaction may predict environmental threat or safety.

  15. The social modulation of pain: others as predictive signals of salience - a systematic review.

    Science.gov (United States)

    Krahé, Charlotte; Springer, Anne; Weinman, John A; Fotopoulou, Aikaterini

    2013-01-01

    Several studies in cognitive neuroscience have investigated the cognitive and affective modulation of pain. By contrast, fewer studies have focused on the social modulation of pain, despite a plethora of relevant clinical findings. Here we present the first review of experimental studies addressing how interpersonal factors, such as the presence, behavior, and spatial proximity of an observer, modulate pain. Based on a systematic literature search, we identified 26 studies on experimentally induced pain that manipulated different interpersonal variables and measured behavioral, physiological, and neural pain-related responses. We observed that the modulation of pain by interpersonal factors depended on (1) the degree to which the social partners were active or were perceived by the participants to possess possibility for action; (2) the degree to which participants could perceive the specific intentions of the social partners; (3) the type of pre-existing relationship between the social partner and the person in pain, and lastly, (4) individual differences in relating to others and coping styles. Based on these findings, we propose that the modulation of pain by social factors can be fruitfully understood in relation to a recent predictive coding model, the free energy framework, particularly as applied to interoception and social cognition. Specifically, we argue that interpersonal interactions during pain may function as social, predictive signals of contextual threat or safety and as such influence the salience of noxious stimuli. The perception of such interpersonal interactions may in turn depend on (a) prior beliefs about interpersonal relating and (b) the certainty or precision by which an interpersonal interaction may predict environmental threat or safety.

  16. Fibromyalgia, milnacipran and experimental pain modulation: study protocol for a double blind randomized controlled trial.

    Science.gov (United States)

    Macian, Nicolas; Pereira, Bruno; Shinjo, Coralie; Dubray, Claude; Pickering, Gisèle

    2015-04-03

    The prevalence of fibromyalgia increases worldwide and is characterized by widespread and chronic pain. Treatment is difficult and includes both drug and non-drug approaches. Milnacipran, an antidepressant, is used for fibromyalgia, with a possible beneficial effect on central pain modulation. Our hypothesis is that the efficacy of milnacipran in fibromyalgia depends on the performance of pain inhibitory controls. A randomized, double blind, clinical trial (NCT01747044) with two parallel groups, in 48 women with fibromyalgia, is planned in the Clinical Pharmacology Center, University Hospital, Clermont-Ferrand, France. Conditioned pain modulation (estimated with thermal stimuli using a numeric pain rating scale), the primary endpoint measure, is evaluated before and one month after treatment with milnacipran or placebo. Secondary outcome measures include the predictability of pain descending pathways performance for milnacipran efficacy, tolerance and cognitive function. Data analysis is performed using mixed models; the tests are two-sided, with a type I error set at alpha = 0.05. Not only will this trial allow estimation of the beneficial effect of milnacipran on pain and on descending pain pathways but it will also evaluate whether the performance of this modulatory system could be predictive of its efficacy in alleviating pain. This method would allow clinicians to take a pro-active attitude by performing a rapid psychophysical test before starting milnacipran treatment and would avoid unnecessary prescription while preventing therapeutic failure in patients who often face this recurrent problem. ClinicalTrials.gov NCT01747044 .

  17. A comparison between the neural correlates of laser and electric pain stimulation and their modulation by expectation.

    Science.gov (United States)

    Hird, E J; Jones, A K P; Talmi, D; El-Deredy, W

    2018-01-01

    Pain is modulated by expectation. Event-related potential (ERP) studies of the influence of expectation on pain typically utilise laser heat stimulation to provide a controllable nociceptive-specific stimulus. Painful electric stimulation has a number of practical advantages, but is less nociceptive-specific. We compared the modulation of electric versus laser-evoked pain by expectation, and their corresponding pain-evoked and anticipatory ERPs. We developed understanding of recognised methods of laser and electric stimulation. We tested whether pain perception and neural activity induced by electric stimulation was modulated by expectation, whether this expectation elicited anticipatory neural correlates, and how these measures compared to those associated with laser stimulation by eliciting cue-evoked expectations of high and low pain in a within-participant design. Despite sensory and affective differences between laser and electric pain, intensity ratings and pain-evoked potentials were modulated equivalently by expectation, though ERPs only correlated with pain ratings in the laser pain condition. Anticipatory correlates differentiated pain intensity expectation to laser but not electric pain. Previous studies show that laser-evoked potentials are modulated by expectation. We extend this by showing electric pain-evoked potentials are equally modulated by expectation, within the same participants. We also show a difference between the pain types in anticipation. Though laser-evoked potentials express a stronger relationship with pain perception, both laser and electric stimulation may be used to study the modulation of pain-evoked potentials by expectation. Anticipatory-evoked potentials are elicited by both pain types, but they may reflect different processes. Copyright © 2017. Published by Elsevier B.V.

  18. Review of overlap between thermoregulation and pain modulation in fibromyalgia

    Science.gov (United States)

    Larson, Alice A.; Pardo, José V.; Pasley, Jeffrey D.

    2013-01-01

    Fibromyalgia syndrome is characterized by widespread pain that is exacerbated by cold and stress but relieved by warmth. We review the points along thermal and pain pathways where temperature may influence pain. We also present evidence addressing the possibility that brown adipose tissue activity is linked to the pain of fibromyalgia given that cold initiates thermogenesis in brown adipose tissue via adrenergic activity, while warmth suspends thermogenesis. Although females have a higher incidence of fibromyalgia as well as more resting thermogenesis, they are less able to recruit brown adipose tissue in response to chronic stress than males. In addition, conditions that are frequently comorbid with fibromyalgia compromise brown adipose activity making it less responsive to sympathetic stimulation. This results in lower body temperatures, lower metabolic rates, and lower circulating cortisol/corticosterone in response to stress - characteristics of fibromyalgia. In the periphery, sympathetic nerves to brown adipose also project to surrounding tissues, including tender points characterizing fibromyalgia. As a result, the musculoskeletal hyperalgesia associated with conditions like fibromyalgia may result from referred pain in the adjacent muscle and skin. PMID:23887348

  19. Observing back pain provoking lifting actions modulates corticomotor excitability of the observer's primary motor cortex.

    Science.gov (United States)

    Lehner, Rea; Meesen, Raf; Wenderoth, Nicole

    2017-07-01

    Observing another person experiencing exogenously inflicted pain (e.g. by a sharp object penetrating a finger) modulates the excitability of the observer' primary motor cortex (M1). By contrast, far less is known about the response to endogenously evoked pain such as sudden back pain provoked by lifting a heavy object. Here, participants (n=26) observed the lifting of a heavy object. During this action the actor (1) flexed and extended the legs (LEG), (2) flexed and extended the back (BACK) or (3) flexed and extended the back which caused visible pain (BACKPAIN). Corticomotor excitability was measured by applying a single transcranial magnetic stimulation pulse to the M1 representation of the muscle erector spinae and participants scored their perception of the actor's pain on the numeric pain rating scale (NPRS). The participants scored vicarious pain as highest during the BACKPAIN condition and lowest during the LEG condition. MEP size was significantly lower for the LEG than the BACK and BACKPAIN condition. Although we found no statistical difference in the motor-evoked potential (MEP) size between the conditions BACK and BACKPAIN, there was a significant correlation between the difference in NPRS scores between the conditions BACKPAIN and BACK and the difference in MEP size between these conditions. Participants who believed the vicarious pain to be much stronger in the BACKPAIN than in the BACK condition also exhibited higher MEPs for the BACKPAIN than the BACK condition. Our results indicate that observing how others lift heavy objects facilitates motor representations of back muscles in the observer. Modulation occurs in a movement-specific manner and is additionally modulated by the extent to which the participants perceived the actor's pain. Our findings suggest that movement observation might be a promising paradigm to study the brain's response to back pain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Descending pain modulation and its interaction with peripheral sensitization following sustained isometric muscle contraction in fibromyalgia

    DEFF Research Database (Denmark)

    Ge, H-Y; Nie, Hongling; Graven-Nielsen, Thomas

    2012-01-01

    OBJECTIVE: Sustained isometric muscle contraction (fatiguing contraction) recruits segmental and/or extrasegmental descending inhibition in healthy subjects but not in fibromyalgia (FM). We hypothesized that fatiguing contraction may shift descending pain modulation from inhibition towards...... facilitation and that the effect of descending pain modulation be dependent on peripheral muscle pain sensitivity. METHODS: Pressure pain thresholds (PPT) were measured from 13 points bilaterally in the upper trapezius muscle and from the mid-point bilaterally in the tibialis anterior before-, immediately......) than healthy control groups (286.2±24.1s) (P0.05). Following the contraction, PPTs were increased significantly and heterogeneously in the upper trapezius over time, but not, in the tibialis anterior muscle in healthy controls. However, PPT were significantly decreased over time in the tibialis...

  1. Conditioned pain modulation is minimally influenced by cognitive evaluation or imagery of the conditioning stimulus

    Directory of Open Access Journals (Sweden)

    Bernaba M

    2014-11-01

    Full Text Available Mario Bernaba, Kevin A Johnson, Jiang-Ti Kong, Sean MackeyStanford Systems Neuroscience and Pain Laboratory, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USAPurpose: Conditioned pain modulation (CPM is an experimental approach for probing endogenous analgesia by which one painful stimulus (the conditioning stimulus may inhibit the perceived pain of a subsequent stimulus (the test stimulus. Animal studies suggest that CPM is mediated by a spino–bulbo–spinal loop using objective measures such as neuronal firing. In humans, pain ratings are often used as the end point. Because pain self-reports are subject to cognitive influences, we tested whether cognitive factors would impact on CPM results in healthy humans.Methods: We conducted a within-subject, crossover study of healthy adults to determine the extent to which CPM is affected by 1 threatening and reassuring evaluation and 2 imagery alone of a cold conditioning stimulus. We used a heat stimulus individualized to 5/10 on a visual analog scale as the testing stimulus and computed the magnitude of CPM by subtracting the postconditioning rating from the baseline pain rating of the heat stimulus.Results: We found that although evaluation can increase the pain rating of the conditioning stimulus, it did not significantly alter the magnitude of CPM. We also found that imagery of cold pain alone did not result in statistically significant CPM effect.Conclusion: Our results suggest that CPM is primarily dependent on sensory input, and that the cortical processes of evaluation and imagery have little impact on CPM. These findings lend support for CPM as a useful tool for probing endogenous analgesia through subcortical mechanisms.Keywords: conditioned pain modulation, endogenous analgesia, evaluation, imagery, cold presser test, CHEPS, contact heat-evoked potential stimulator

  2. Modulation of vagal tone enhances gastroduodenal motility and reduces somatic pain sensitivity.

    Science.gov (United States)

    Frøkjaer, J B; Bergmann, S; Brock, C; Madzak, A; Farmer, A D; Ellrich, J; Drewes, A M

    2016-04-01

    The parasympathetic nervous system, whose main neural substrate is the vagus nerve, exerts a fundamental antinociceptive role and influences gastrointestinal sensori-motor function. Our research question was to whether combined electrical and physiological modulation of vagal tone, using transcutaneous electrical vagal nerve stimulation (t-VNS) and deep slow breathing (DSB) respectively, could increase musculoskeletal pain thresholds and enhance gastroduodenal motility in healthy subjects. Eighteen healthy subjects were randomized to a subject-blinded, sham-controlled, cross-over study with an active protocol including stimulation of auricular branch of the vagus nerve, and breathing at full inspiratory capacity and forced full expiration. Recording of cardiac derived parameters including cardiac vagal tone, moderate pain thresholds to muscle, and bone pressure algometry, conditioned pain modulation using a cold pressor test and a liquid meal ultrasonographic gastroduodenal motility test were performed. Cardiac vagal tone increased during active treatment with t-VNS and DSB compared to sham (p = 0.009). In comparison to sham, thresholds to bone pain increased (p = 0.001), frequency of antral contractions increased (p = 0.004) and gastroduodenal motility index increased (p = 0.016) with active treatment. However, no effect on muscle pain thresholds and conditioned pain modulation was seen. This experimental study suggests that this noninvasive approach with combined electrical and physiological modulation of vagal tone enhances gastroduodenal motility and reduces somatic pain sensitivity. These findings warrant further investigation in patients with disorders characterized with chronic pain and gastrointestinal dysmotility such as functional dyspepsia and irritable bowel syndrome. © 2016 John Wiley & Sons Ltd.

  3. [Lumbar post-laminectomy syndrome: II. Pain management using neuro-modulation techniques].

    Science.gov (United States)

    Robaina Padrón, F J

    2008-02-01

    The application of neuro-modulation techniques in general is currently gaining acceptance in various aspects of medicine. Neuro-modulation is defined as: "Therapeutical interventions using implantable devices to modify the functioning of central, peripheral and autonomic nervous systems". Following lumbar disc surgery, or lumbar spine surgery in general, several chronic pain syndromes can result, either in the lumbar region and/or in the lower limbs. The current status is for the application of surgery to the degenerative spine (degenerative disc disease and lumbar stenosis) for the relief of chronic pain. A review of the methodology of evidence based medicine, show that the instrumented and fusion techniques are not the answered despite 20 years of the use of these techniques following failure of surgery for the relief of back pain syndrome. Neuro-modulation techniques represent a step in the right direction for the management of these chronic pain syndromes. Frequently they enable the resolution of chronic pain following spine surgery without having to resort to repeat surgery. We describe here the different neuro-modulation techniques (spinal cord stimulation, spinal drug infusions) which can be used in the case of back surgery failure, and we describe technical aspects and "tricks of the trade" for the correct implantation of the devices used in techniques. Neuro-modulation techniques are applied to the management of chronic pain following disc surgery and represent a valid alternative to repeat surgery and/or arthrodesis (instrumented or not). Neurosurgeons are again called to play active roles in the field of neuro-modulation for the treatment.

  4. The role of cardiovascular activity in fibromyalgia and conditioned pain modulation.

    Science.gov (United States)

    Chalaye, Philippe; Lafrenaye, Sylvie; Goffaux, Philippe; Marchand, Serge

    2014-06-01

    Fibromyalgia (FM) is a chronic widespread pain condition of unknown origin. Reduced endogenous pain inhibition could be related to high pain sensitivity in FM. Associations between conditioned pain modulation (CPM) and cardiovascular responses to pain have been observed in healthy subjects (HS). Because reduced cardiovascular reactivity to various stressors has been reported in FM patients, we investigated relationships between CPM and cardiovascular response to the cold pressor test (CPT) in 22 FM patients and 25 HS. CPM was evaluated by comparing pain intensity produced by a 120-second heat test stimulus (HTS) before and after a CPT (2minutes, 12°C). The CPT, used to activate CPM, produced greater pain intensity in FM patients. Patients with FM had higher heart rates than HS at baseline and during CPT. Higher heart rate was related with higher pain intensity during the CPT. Blood pressure increments during CPT were weaker in the FM group. CPM was less effective in FM patients than in HS. Importantly, systolic blood pressure responses during CPT were positively related to CPM effectiveness, suggesting that reduced blood pressure response during the conditioning stimulus could be involved in CPM dysfunction in the FM group. Higher heart rate could be implicated in the greater sensitivity to cold pain in FM. Patients with FM have reduced blood pressure response to a painful CPT. Reduced cardiovascular reactivity to pain could have important involvement in diminished endogenous pain inhibition efficacy and FM pathophysiology. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  5. Descending pain modulation in irritable bowel syndrome (IBS): a systematic review and meta-analysis.

    Science.gov (United States)

    Chakiath, Rosemary J; Siddall, Philip J; Kellow, John E; Hush, Julia M; Jones, Mike P; Marcuzzi, Anna; Wrigley, Paul J

    2015-12-10

    Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. While abdominal pain is a dominant symptom of IBS, many sufferers also report widespread hypersensitivity and present with other chronic pain conditions. The presence of widespread hypersensitivity and extra-intestinal pain conditions suggests central nervous dysfunction. While central nervous system dysfunction may involve the spinal cord (central sensitisation) and brain, this review will focus on one brain mechanism, descending pain modulation. We will conduct a comprehensive search for the articles indexed in the databases Ovid MEDLINE, Ovid Embase, Ovid PsycINFO and Cochrane Central Register of Controlled Trial (CENTRAL) from their inception to August 2015, that report on any aspect of descending pain modulation in irritable bowel syndrome. Two independent reviewers will screen studies for eligibility, assess risk of bias and extract relevant data. Results will be tabulated and, if possible, a meta-analysis will be carried out. The systematic review outlined in this protocol aims to summarise current knowledge regarding descending pain modulation in IBS. PROSPERO CRD42015024284.

  6. TRANSCUTANEOUS ELECTRIC NERVE STIMULATION IN MODULATION OF PAIN OF TENDER POINTS IN SYNDROME FIBROMYALGIA: CASE STUDY

    Directory of Open Access Journals (Sweden)

    Isabel Mara Magalhães Rori

    2008-08-01

    Full Text Available The Fibromyalgia is a syndrome of pain and chronic diffuse, characterized by the presence of at least 11 of 18 points called anatomically specific tender points, painful on palpation. As the pain diffuse the main symptom of fibromyalgia. The current treatment is focused mainly to the reduction of symptoms. Physiotherapy has animportant role in improving the control of pain. This study aimed to verify the effectiveness of the main TENS of low frequency and high intensity in modulating pain of tender points of patients with fibromyalgia. For this was a case study of patient R. S. S., 38-yearold female carrier of the syndrome of fibromyalgia attended school in the clinic of the Faculty of Integrated Ceará (FISIOFIC. The patient was treated with the TENS-pain Acupuncture points in a total of twelve care and pain assessed before starting treatment and after three attendants. There was a significant reduction in pain intensity at 77.7% of the tender points in the second evaluation and 88.8% of the points in the other assessments. It was concluded that there was a reduction in the pain of tender points of the patient showing the analgesia promoted by TENS, so it should be used as a complementary treatment programs associated with other treatments and also served as a good technique to locate the tender points.

  7. Reduced modulation of pain in older adults following isometric and aerobic exercise

    Science.gov (United States)

    Naugle, Kelly M.; Naugle, Keith E.; Riley, Joseph L.

    2016-01-01

    Laboratory based studies show that acute aerobic and isometric exercise reduces sensitivity to painful stimuli in young healthy individuals, indicative of a hypoalgesic response. However, little is known regarding the effect of aging on exercise-induced hypoalgesia (EIH). The purpose of this study was to examine age differences in EIH following submaximal isometric exercise, and moderate and vigorous aerobic exercise. Healthy older and younger adults completed one training session and four testing sessions consisting of either a submaximal isometric handgrip exercise, vigorous or moderate intensity stationary cycling, or quiet rest (control). The following measures were taken pre and post exercise/quiet rest: 1) pressure pain thresholds (PPTs), 2) suprathreshold pressure pain ratings, 3) pain ratings during 30-s of prolonged noxious heat stimulation, and 3) temporal summation of heat pain. The results revealed age differences in EIH following isometric and aerobic exercise, with younger adults experiencing greater EIH compared to older adults. The age differences in EIH varied across pain induction techniques and exercise type. These results provide evidence for abnormal pain modulation following acute exercise in older adults. PERSPECTIVE This article enhances our understanding of the influence of a single bout of exercise on pain sensitivity and perception in healthy older compared to younger adults. This knowledge could potentially help clinicians optimize exercise as a method of pain management. PMID:26993959

  8. Peripheral Receptor Mechanisms Underlying Orofacial Muscle Pain and Hyperalgesia

    Science.gov (United States)

    Saloman, Jami L.

    Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) are severely debilitating and affect approximately 12% of the population. Identifying peripheral nociceptive mechanisms underlying mechanical hyperalgesia, a prominent feature of persistent muscle pain, could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. This study provides evidence of functional interactions between ligand-gated channels, P2X3 and TRPV1/TRPA1, in trigeminal sensory neurons, and proposes that these interactions underlie the development of mechanical hyperalgesia. In the masseter muscle, direct P2X3 activation, via the selective agonist αβmeATP, induced a dose- and time-dependent hyperalgesia. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810, or the TRPA1 antagonist, AP18. P2X3 was co-expressed with both TRPV1 and TRPA1 in masseter muscle afferents confirming the possibility for intracellular interactions. Moreover, in a subpopulation of P2X3 /TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly potentiated following P2X3 activation. Inhibition of Ca2+-dependent kinases, PKC and CaMKII, prevented P2X3-mechanical hyperalgesia whereas blockade of Ca2+-independent PKA did not. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal sensory neurons. Significant phosphorylation was observed at 15 minutes, the time point at which behavioral hyperalgesia was prominent. Similar data were obtained regarding another nonselective cation channel, the NMDA receptor (NMDAR). Our data propose P2X3 and NMDARs interact with TRPV1 in a facilitatory manner, which could contribute to the peripheral sensitization underlying masseter hyperalgesia. This study offers novel mechanisms by which individual pro-nociceptive ligand

  9. Thermal modelling of PV module performance under high ambient temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Diarra, D.C.; Harrison, S.J. [Queen' s Univ., Kingston, ON (Canada). Dept. of Mechanical and Materials Engineering Solar Calorimetry Lab; Akuffo, F.O. [Kwame Nkrumah Univ. of Science and Technology, Kumasi (Ghana). Dept. of Mechanical Engineering

    2005-07-01

    When predicting the performance of photovoltaic (PV) generators, the actual performance is typically lower than test results conducted under standard test conditions because the radiant energy absorbed in the module under normal operation raises the temperature of the cell and other multilayer components. The increase in temperature translates to a lower conversion efficiency of the solar cells. In order to address these discrepancies, a thermal model of a characteristic PV module was developed to assess and predict its performance under real field-conditions. The PV module consisted of monocrystalline silicon cells in EVA between a glass cover and a tedlar backing sheet. The EES program was used to compute the equilibrium temperature profile in the PV module. It was shown that heat is dissipated towards the bottom and the top of the module, and that its temperature can be much higher than the ambient temperature. Modelling results indicate that 70-75 per cent of the absorbed solar radiation is dissipated from the solar cells as heat, while 4.7 per cent of the solar energy is absorbed in the glass cover and the EVA. It was also shown that the operating temperature of the PV module decreases with increased wind speed. 2 refs.

  10. α2δ Modulators for management of compression neuropathic pain: A review of three case series

    Directory of Open Access Journals (Sweden)

    Tariq A Tramboo

    2009-01-01

    Conclusion: These results indicate the effectiveness of a2d modulators for management of neuropathic pain secondary to compression radiculopathy. The results also suggest a possible therapeutic superiority of LYRICA over locally available generic brands of pregabalin and gabapentin. These findings need to be further examined in randomized, controlled trials.

  11. Neuroplasticity Underlying the Comorbidity of Pain and Depression

    Directory of Open Access Journals (Sweden)

    Lisa Doan

    2015-01-01

    Full Text Available Acute pain induces depressed mood, and chronic pain is known to cause depression. Depression, meanwhile, can also adversely affect pain behaviors ranging from symptomology to treatment response. Pain and depression independently induce long-term plasticity in the central nervous system (CNS. Comorbid conditions, however, have distinct patterns of neural activation. We performed a review of the changes in neural circuitry and molecular signaling pathways that may underlie this complex relationship between pain and depression. We also discussed some of the current and future therapies that are based on this understanding of the CNS plasticity that occurs with pain and depression.

  12. Respiratory hypoalgesia? Breath-holding, but not respiratory phase modulates nociceptive flexion reflex and pain intensity.

    Science.gov (United States)

    Jafari, Hassan; Van de Broek, Karlien; Plaghki, Léon; Vlaeyen, Johan W S; Van den Bergh, Omer; Van Diest, Ilse

    2016-03-01

    Several observations suggest that respiratory phase (inhalation vs. exhalation) and post-inspiratory breath-holds could modulate pain and the nociceptive reflex. This experiment aimed to investigate the role of both mechanisms. Thirty-two healthy participants received supra-threshold electrocutaneous stimulations to elicit both the Nociceptive Flexion Reflex (NFR) and pain, either during spontaneous inhalations or exhalations, or during three types of instructed breath-holds: following exhalation, at mid-inhalation and at full-capacity inhalation. Whether the electrocutaneous stimulus was applied during inhalation or exhalation did not affect the NFR or pain. Self-reported pain was reduced and the NFR was increased during breath-holding compared to spontaneous breathing. Whereas the type of breath-hold did not impact on self-reported pain, breath-holds at full-capacity inhalation and following exhalation were associated with a lower NFR amplitude compared to breath-holds at mid-inhalation. The present findings confirm that breath-holding can modulate pain (sensitivity) and suggest that both attentional distraction and changes in vagal activity may underlie the observed effects. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Turning down the thermostat: Modulating the endocannabinoid system in ocular inflammation and pain

    Directory of Open Access Journals (Sweden)

    J. Thomas Toguri

    2016-09-01

    Full Text Available The endocannabinoid system (ECS has emerged as an important regulator of both physiological and pathological processes. Notably, this endogenous system plays a key role in the modulation of pain and inflammation in a number of tissues. The components of the ECS, including endocannabinoids, their cognate enzymes and cannabinoid receptors, are localized in the eye, and evidence indicates that ECS modulation plays a role in ocular disease states. Of these diseases, ocular inflammation presents a significant medical problem, given that current clinical treatments can be ineffective or are associated with intolerable side-effects. Furthermore, a prominent comorbidity of ocular inflammation is pain, including neuropathic pain, for which therapeutic options remain limited. Recent evidence supports the use of drugs targeting the ECS for the treatment of ocular inflammation and pain in animal models; however, the potential for therapeutic use of cannabinoid drugs in the eye has not been thoroughly investigated at this time. This review will highlight evidence from experimental studies identifying components of the ocular ECS and discuss the functional role of the ECS during different ocular inflammatory disease states, including uveitis and corneal keratitis. Candidate ECS targeted therapies will be discussed, drawing on experimental results obtained from both ocular and non-ocular tissue(s, together with their potential application for the treatment of ocular inflammation and pain.

  14. Teaching Pain Management in Interprofessional Medical Education: A Review of Three Portal of Geriatric Online Education Modules.

    Science.gov (United States)

    Madaus, Stacy M; Lim, Lionel S

    2016-10-01

    Chronic pain is an international healthcare crisis that affects an estimated 1.5 billion individuals worldwide, but pain management is not emphasized in the medical school curriculum, and thus supplemental education is essential. The Portal of Geriatric Online Education (POGOe) is a free repository of teaching modules for use by geriatric educators and learners. This article highlights three teaching modules available on this site: It's My Old Back Again: An Approach to Diagnosing and Managing Back Pain in the Older Adult (POGOe ID: 21670), Computer Based Learning Workbook, Third Edition module on Pain Management (POGOe ID: 21036), and Aging Q3 Curriculum on Pain Management of Older Adult Patients (POGOe ID: 21187). These modules were chosen based on their ability to address the major topics that the International Association for the Study of Pain proposes should be included in medical school curricula: mulitdimensional nature of pain, pain assessment and measurement, management of pain, and clinical conditions resulting in pain in older adults. They were also selected for their ability to be adapted for interprofessional education and how well they integrate basic science and clinical principles. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  15. Pulsed radiofrequency of brachial plexus under ultrasound guidance for refractory stump pain: a case report

    Directory of Open Access Journals (Sweden)

    Zheng B

    2017-11-01

    Full Text Available Bixin Zheng, Li Song, Hui Liu Department of Pain Management, West China Hospital of Sichuan University, Chengdu, China Abstract: The post-amputation (pain syndrome, including stump pain, phantom limb sensation, and phantom limb pain is common but difficult to treat. Refractory stump pain in the syndrome is an extremely challenging and troublesome clinical condition. Patients respond poorly to drugs, nerve blocks, and other effective treatments like spinal cord stimulation and surgery. Pulsed radiofrequency (PRF technique has been shown to be effective in reducing neuropathic pain. This report describes a patient with persistent and refractory upper limb stump pain being successfully relieved with PRF of brachial plexus under ultrasound guidance after a 6-month follow-up period, suggesting that PRF may be considered as an alternative treatment for refractory stump-neuroma pain. Keywords: ultrasound guidance, pulsed radiofrequency, brachial plexus, refractory stump pain 

  16. Prognostic factors and underlying mechanisms in chronic low back pain

    NARCIS (Netherlands)

    Vos-van der Hulst, Marije

    2009-01-01

    Low back pain (LBP) is defined as pain localised between the 12th rib and the inferior gluteal folds. At any moment, about 15% of adults have LBP. In the majority of the cases, LBP is a self-limiting disease and 90% of the attacks of LBP recover within 6-8 weeks. A minority of subjects with

  17. Disordered conditioned pain modulation system in patients with posttraumatic cold intolerance.

    Science.gov (United States)

    Smits, E S; Selles, R W; Huygen, F J P; Duraku, L S; Hovius, S E R; Walbeehm, E T

    2014-01-01

    Conditioned pain modulation (CPM) is a phenomenon of 'pain inhibiting pain' that is important for understanding idiopathic pain syndromes. Because the pathophysiology of posttraumatic cold intolerance is still unknown but it could involve similar mechanisms as idiopathic pain syndromes, we evaluated the functioning of the CPM system in patients with posttraumatic cold intolerance compared to healthy controls. Fourteen healthy controls and 24 patients diagnosed with cold intolerance using the Cold Intolerance Symptom Severity questionnaire were included in the study. Of the 24 patients with cold intolerance, 11 had a nerve lesion and 13 an amputation of one or more digits. To quantify the CPM, pain threshold for mechanical pressure was measured at the affected region as a baseline measure. Then, the contralateral hand received a cold stimulus of ice water to evoke the noxious conditioning. After the cold stimulus, the pain threshold for mechanical pressure was determined again. The absolute and relative changes in algometer pressure (CPM effect) between pre- and post-conditioning were significantly smaller in the cold intolerance group compared to the control group (absolute p = 0.019, relative p = 0.004). The CPM effect was significantly different between the control group and the subgroups of nerve lesion (p = 0.003) and amputation patients (p = 0.011). In this study, we found a CPM effect after a cold stimulus in both controls and patients. A significant weaker CPM effect compared to the controls was found, as in other chronic pain conditions. The CPM system within patients with cold intolerance is altered. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  18. Over-, under- and misuse of pain treatment in Germany

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    Dietl, Markus

    2011-01-01

    Full Text Available Background: The HTA-report (Health Technology Assessment deals with over- and undertreatment of pain therapy. Especially in Germany chronic pain is a common reason for the loss of working hours and early retirement. In addition to a reduction in quality of life for the affected persons, chronic pain is therefore also an enormous economic burden for society. Objectives: Which diseases are in particular relevant regarding pain therapy? What is the social-medical care situation regarding pain facilities in Germany? What is the social-medical care situation in pain therapy when comparing on international level? Which effects, costs or cost-effects can be seen on the micro-, meso- and macro level with regard to pain therapy? Among which social-medical services in pain therapy is there is an over- or undertreatment with regard to the micro-, meso- and macro level? Which medical and organisational aspects that have an effect on the costs and/or cost-effectiveness have to be particularly taken into account with regard to pain treatment/chronic pain? What is the influence of the individual patient's needs (micro level in different situations of pain (e. g. palliative situation on the meso- and macro level? Which social-medical and ethical aspects for an adequate treatment of chronic pain on each level have to be specially taken into account? Is the consideration of these aspects appropriate to avoid over- or undertreatment? Are juridical questions included in every day care of chronic pain patients, mainly in palliative care? On which level can appropriate interventions prevent over- or undertreatment? Methods: A systematic literature research is done in 35 databases. In the HTA, reviews, epidemiological and clinical studies and economic evaluations are included which report about pain therapy and in particular palliative care in the years 2005 till 2010. Results: 47 studies meet the inclusion criteria. An undertreatment of acupuncture, over- and misuse

  19. High frequency electrical stimulation concurrently induces central sensitization and ipsilateral inhibitory pain modulation.

    Science.gov (United States)

    Vo, L; Drummond, P D

    2013-03-01

    In healthy humans, analgesia to blunt pressure develops in the ipsilateral forehead during various forms of limb pain. The aim of the current study was to determine whether this analgesic response is induced by ultraviolet B radiation (UVB), which evokes signs of peripheral sensitization, or by high-frequency electrical stimulation (HFS), which triggers signs of central sensitization. Before and after HFS and UVB conditioning, sensitivity to heat and to blunt and sharp stimuli was assessed at and adjacent to the treated site in the forearm. In addition, sensitivity to blunt pressure was measured bilaterally in the forehead. The effect of ipsilateral versus contralateral temple cooling on electrically evoked pain in the forearm was then examined, to determine whether HFS or UVB conditioning altered inhibitory pain modulation. UVB conditioning triggered signs of peripheral sensitization, whereas HFS conditioning triggered signs of central sensitization. Importantly, ipsilateral forehead analgesia developed after HFS but not UVB conditioning. In addition, decreases in electrically evoked pain at the HFS-treated site were greater during ipsilateral than contralateral temple cooling, whereas decreases at the UVB-treated site were similar during both procedures. HFS conditioning induced signs of central sensitization in the forearm and analgesia both in the ipsilateral forehead and the HFS-treated site. This ipsilateral analgesia was not due to peripheral sensitization or other non-specific effects, as it failed to develop after UVB conditioning. Thus, the supra-spinal mechanisms that evoke central sensitization might also trigger a hemilateral inhibitory pain modulation process. This inhibitory process could sharpen the boundaries of central sensitization or limit its spread. © 2012 European Federation of International Association for the Study of Pain Chapters.

  20. Expectation modulates repetition priming under high stimulus variability

    Science.gov (United States)

    Olkkonen, Maria; Aguirre, Geoffrey K.; Epstein, Russell A.

    2017-01-01

    Neural responses to stimuli are often attenuated by repeated presentation. When observed in blood oxygen level-dependent signals, this attenuation is known as fMRI adaptation (fMRIa) or fMRI repetition suppression. According to a prominent account, fMRIa reflects the fulfillment of perceptual expectations during recognition of repeated items (Summerfield, Trittschuh, Monti, Mesulam, & Egner, 2008). Supporting this idea, expectation has been shown to modulate fMRIa under some circumstances; however, it is not currently known whether expectation similarly modulates recognition performance. To address this lacuna, we measured behavioral and fMRI responses to faces while varying the extent to which each stimulus was informative about its successor. Behavioral priming was greater when repetitions were more likely, suggesting that recognition was facilitated by the expectation than an item would repeat. Notably, this effect was only observed when stimuli were drawn from a broad set of faces including many ethnicities and both genders, but not when stimuli were drawn from a narrower face set, thus making repetitions less informative. Moreover, expectation did not modulate fMRIa in face-selective cortex, contrary to previous studies, although an exploratory analysis indicated that it did so in a medial frontal region. These results support the idea that expectation modulates recognition efficiency, but insofar as behavioral effects of expectation were not accompanied by fMRI effects in visual cortex, they suggest that fMRIa cannot be entirely explained in terms of fulfilled expectations. PMID:28617928

  1. Chronic Pain in People with an Intellectual Disability: Under-Recognised and Under-Treated?

    Science.gov (United States)

    McGuire, B. E.; Daly, P.; Smyth, F.

    2010-01-01

    Aim: To examine the nature, prevalence and impact of chronic pain in adults with an intellectual disability (ID) based on carer report. Methods: Postal questionnaires were sent to 250 care-givers and 157 responses were received (63%). Results: Chronic pain was reported in 13% of the sample (n = 21), 6.3% had pain in two sites and 2% had pain in…

  2. 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.

  3. 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.

  4. Effects of the carrier frequency of interferential current on pain modulation in patients with chronic nonspecific low back pain: a protocol of a randomised controlled trial

    Science.gov (United States)

    2013-01-01

    Background Low back pain is an important public health problem that is associated with poor quality of life and disability. Among the electrophysical treatments, interferential current (IFC) has not been studied in patients with low back pain in a high-quality randomised controlled trial examining not only pain, but pain mechanisms and function. Methods/design A three-arm randomised controlled trial with patient and assessor blinded to the group allocation. One hundred fifty patients with chronic, nonspecific low back pain from outpatient physical therapy clinics in Brazil. The patients will be randomly allocated into 3 groups (IFC 1 kHz, IFC 4 kHz or Placebo IFC). The interferential current will be applied three days per week (30 minutes per session) over four weeks. Primary outcome: Pain intensity. Secondary outcomes: The pressure pain threshold, global impression of recovery, disability, function, conditioned pain modulation and temporal summation of pain, discomfort caused by the current. All outcomes will be measured at 4 weeks and 4 months after randomisation. The between-group differences will be calculated by using linear mixed models and Tukey’s post-hoc tests. Discussion The use of a placebo group and double-blinding assessor and patients strengthen this study. The present study is the first to compare different IFC carrier frequencies in patients with chronic low back pain. Trial registration Brazilian Registry of Clinical Trials: http://RBR-8n4hg2 PMID:23802771

  5. Effects of the carrier frequency of interferential current on pain modulation in patients with chronic nonspecific low back pain: a protocol of a randomised controlled trial.

    Science.gov (United States)

    Corrêa, Juliana Barbosa; Costa, Leonardo Oliveira Pena; de Oliveira, Naiane Teixeira Bastos; Sluka, Kathleen A; Liebano, Richard Eloin

    2013-06-27

    Low back pain is an important public health problem that is associated with poor quality of life and disability. Among the electrophysical treatments, interferential current (IFC) has not been studied in patients with low back pain in a high-quality randomised controlled trial examining not only pain, but pain mechanisms and function. A three-arm randomised controlled trial with patient and assessor blinded to the group allocation. One hundred fifty patients with chronic, nonspecific low back pain from outpatient physical therapy clinics in Brazil. The patients will be randomly allocated into 3 groups (IFC 1 kHz, IFC 4 kHz or Placebo IFC). The interferential current will be applied three days per week (30 minutes per session) over four weeks. Pain intensity. The pressure pain threshold, global impression of recovery, disability, function, conditioned pain modulation and temporal summation of pain, discomfort caused by the current. All outcomes will be measured at 4 weeks and 4 months after randomisation. The between-group differences will be calculated by using linear mixed models and Tukey's post-hoc tests. The use of a placebo group and double-blinding assessor and patients strengthen this study. The present study is the first to compare different IFC carrier frequencies in patients with chronic low back pain. Brazilian Registry of Clinical Trials: http://RBR-8n4hg2.

  6. Modulation of endothelial glycocalyx structure under inflammatory conditions.

    Science.gov (United States)

    Kolářová, Hana; Ambrůzová, Barbora; Svihálková Šindlerová, Lenka; Klinke, Anna; Kubala, Lukáš

    2014-01-01

    The glycocalyx of the endothelium is an intravascular compartment that creates a barrier between circulating blood and the vessel wall. The glycocalyx is suggested to play an important role in numerous physiological processes including the regulation of vascular permeability, the prevention of the margination of blood cells to the vessel wall, and the transmission of shear stress. Various theoretical models and experimental approaches provide data about changes to the structure and functions of the glycocalyx under various types of inflammatory conditions. These alterations are suggested to promote inflammatory processes in vessels and contribute to the pathogenesis of number of diseases. In this review we summarize current knowledge about the modulation of the glycocalyx under inflammatory conditions and the consequences for the course of inflammation in vessels. The structure and functions of endothelial glycocalyx are briefly discussed in the context of methodological approaches regarding the determination of endothelial glycocalyx and the uncertainty and challenges involved in glycocalyx structure determination. In addition, the modulation of glycocalyx structure under inflammatory conditions and the possible consequences for pathogenesis of selected diseases and medical conditions (in particular, diabetes, atherosclerosis, ischemia/reperfusion, and sepsis) are summarized. Finally, therapeutic strategies to ameliorate glycocalyx dysfunction suggested by various authors are discussed.

  7. Modulation of Endothelial Glycocalyx Structure under Inflammatory Conditions

    Directory of Open Access Journals (Sweden)

    Hana Kolářová

    2014-01-01

    Full Text Available The glycocalyx of the endothelium is an intravascular compartment that creates a barrier between circulating blood and the vessel wall. The glycocalyx is suggested to play an important role in numerous physiological processes including the regulation of vascular permeability, the prevention of the margination of blood cells to the vessel wall, and the transmission of shear stress. Various theoretical models and experimental approaches provide data about changes to the structure and functions of the glycocalyx under various types of inflammatory conditions. These alterations are suggested to promote inflammatory processes in vessels and contribute to the pathogenesis of number of diseases. In this review we summarize current knowledge about the modulation of the glycocalyx under inflammatory conditions and the consequences for the course of inflammation in vessels. The structure and functions of endothelial glycocalyx are briefly discussed in the context of methodological approaches regarding the determination of endothelial glycocalyx and the uncertainty and challenges involved in glycocalyx structure determination. In addition, the modulation of glycocalyx structure under inflammatory conditions and the possible consequences for pathogenesis of selected diseases and medical conditions (in particular, diabetes, atherosclerosis, ischemia/reperfusion, and sepsis are summarized. Finally, therapeutic strategies to ameliorate glycocalyx dysfunction suggested by various authors are discussed.

  8. The Role of Parabrachial GABAA Receptors in Pain Modulation in Rats

    Directory of Open Access Journals (Sweden)

    kazem javanmardi

    2013-09-01

    Full Text Available Background & Objective: The parabrachial nucleus is a critical link in the transmission of short latency nociceptive information to midbrain neurons. GABA(A receptors have bidirectional roles in controlling nociception and are abundant in the parabrachial region . We examined the effects of bilateral intra parabrachial microinjection of different doses of the GABA(A receptor agonist, muscimol, and the GABA(A receptor antagonist, bicuculline, on pain modulation using a tail-flick test . Materials & Methods: Rats were anaesthetized with sodium pentobarbital (55 mg/kg and then special cannulas were inserted stereotaxically into the parabrachial nucleus. After 1 week of recovery, the effects of microinjection of muscimol, (62.5, 125,250 ng/side or bicuculline, (50,100,200 ng/side into the parabrachial on tail flick latencies were assessed. Tail-flick latencies were measured for 60 minutes every 5 min after drug microinjection. Results: Microinjection of muscimol (62.5, 125 ng/side and bicuculline (50,100,200 ng/side into the parabrachial did not have any statistically significant effect on tail-flick latency. Administration of, muscimol, (250 ng/side produced thermal hyperalgesia (P<0.05. Conclusion: The results of the present study showed that in this model of pain gaba a receptors in the paracrachial region are not Endogenously activated but these receptors in this region have a potential to affect pain modulation.

  9. Adaptations in responsiveness of brainstem pain-modulating neurons in acute compared with chronic inflammation.

    Science.gov (United States)

    Cleary, Daniel R; Heinricher, Mary M

    2013-06-01

    Despite similar behavioral hypersensitivity, acute and chronic pain have distinct neural bases. We used intraplantar injection of complete Freund's adjuvant to directly compare activity of pain-modulating neurons in the rostral ventromedial medulla (RVM) in acute vs chronic inflammation. Heat-evoked and von Frey-evoked withdrawal reflexes and corresponding RVM neuronal activity were recorded in lightly anesthetized animals either during the first hour after complete Freund's adjuvant injection (acute) or 3 to 10 days later (chronic). Thermal and modest mechanical hyperalgesia during acute inflammation were associated with increases in the spontaneous activity of pain-facilitating ON-cells and suppression of pain-inhibiting OFF-cells. Acute hyperalgesia was reversed by RVM block, showing that the increased activity of RVM ON-cells is necessary for acute behavioral hypersensitivity. In chronic inflammation, thermal hyperalgesia had resolved but mechanical hyperalgesia had become pronounced. The spontaneous discharges of ON- and OFF-cells were not different from those in control subjects, but the mechanical response thresholds for both cell classes were reduced into the innocuous range. RVM block in the chronic condition worsened mechanical hyperalgesia. These studies identify distinct contributions of RVM ON- and OFF-cells to acute and chronic inflammatory hyperalgesia. During early immune-mediated inflammation, ON-cell spontaneous activity promotes hyperalgesia. After inflammation is established, the antinociceptive influence of OFF-cells is dominant, yet the lowered threshold for the OFF-cell pause allows behavioral responses to stimuli that would normally be considered innocuous. The efficacy of OFF-cells in counteracting sensitization of ascending transmission pathways could therefore be an important determining factor in development of chronic inflammatory pain. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All

  10. Nitric oxide modulated the expression of DREAM/calsenilin/KChIP3 in inflammatory pain of rats.

    Science.gov (United States)

    Jin, Hong-Bo; Yang, Yong-Liang; Song, Ying-Li; Yang, Yong-Bin; Li, Yu-Rong

    2012-12-01

    Downstream regulatory element antagonistic modulator (DREAM) is a critical transcriptional repressor for pain modulation. The role of nitric oxide (NO) plays in modulating DREAM pain pathway in the periphery is unclear. Therefore, we investigated the role of the NO in modulation of the expression of DREAM in formalin-induced rat inflammatory pain models. Male Sprague-Dawley rats were randomly distributed into four groups: the normal group, formalin test group, Nω-nitro-L-arginine (l-NNA) group, and morphine group. One hundred microliters of 2.5 % formalin was injected into the plantar surface of the right hindpaw of rats. l-NNA (40 nmol/L) and morphine (40 nmol/L) were injected intrathecally in the hindpaw before formalin injection. The nociceptive behavioral reaction was recorded. After the formalin test, the expression of DREAM mRNA and protein in the spinal cord of the four groups were measured. The nociceptive reaction induced by injection of formalin exhibited two phases. Morphine and l-NNA significantly decreased pain scores of the second phase. The expression of DREAM was significantly increased in the rat spinal cord after formalin-induced pain. Morphine significantly upregulated the expression of DREAM, and the formalin-induced upregulation was significantly attenuated by l-NNA. NO may play an important role in the DREAM pathway modulation of inflammatory pain.

  11. µ-Conotoxins Modulating Sodium Currents in Pain Perception and Transmission: A Therapeutic Potential

    Directory of Open Access Journals (Sweden)

    Elisabetta Tosti

    2017-09-01

    Full Text Available The Conus genus includes around 500 species of marine mollusks with a peculiar production of venomous peptides known as conotoxins (CTX. Each species is able to produce up to 200 different biological active peptides. Common structure of CTX is the low number of amino acids stabilized by disulfide bridges and post-translational modifications that give rise to different isoforms. µ and µO-CTX are two isoforms that specifically target voltage-gated sodium channels. These, by inducing the entrance of sodium ions in the cell, modulate the neuronal excitability by depolarizing plasma membrane and propagating the action potential. Hyperexcitability and mutations of sodium channels are responsible for perception and transmission of inflammatory and neuropathic pain states. In this review, we describe the current knowledge of µ-CTX interacting with the different sodium channels subtypes, the mechanism of action and their potential therapeutic use as analgesic compounds in the clinical management of pain conditions.

  12. 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...

  13. Systemic Exercise-Induced Hypoalgesia Following Isometric Exercise Reduces Conditioned Pain Modulation

    DEFF Research Database (Denmark)

    Alsouhibani, Ali; Vaegter, Henrik Bjarke; Hoeger Bement, Marie

    2018-01-01

    Objective: Physically active individuals show greater conditioned pain modulation (CPM) compared with less active individuals. Understanding the effects of acute exercise on CPM may allow for a more targeted use of exercise in the management of pain. This study investigated the effects of acute...... isometric exercise on CPM. In addition, the between-session and within-session reliability of CPM was investigated. Design: Experimental, randomized crossover study. Setting: Laboratory at Marquette University. Subjects: Thirty healthy adults (19.3±1.5 years, 15 males). Methods: Subjects underwent CPM....... Results: PPTs increased during ice water immersion (i.e., CPM), and quadriceps PPT increased after exercise (P CPM decreased similarly following exercise and quiet rest (P > 0.05). CPM within-session reliability was fair to good (intraclass correlation coefficient [ICC] = 0...

  14. Atypical central pain processing in sensory modulation disorder: absence of temporal summation and higher after-sensation.

    Science.gov (United States)

    Bar-Shalita, T; Vatine, J-J; Yarnitsky, D; Parush, S; Weissman-Fogel, I

    2014-02-01

    Sensory over-responsivity (SOR), a subtype of the proposed sensory modulation disorder (SMD), is characterized by over-responsiveness to stimuli in several sensory modalities. SMD individuals demonstrate abnormal responses to naturally occurring stimuli in a manner that interferes with daily life participation. Previous psychophysical testing of the somatosensory system revealed that SOR individuals rated pain sensations higher than controls, demonstrating hyperalgesia that can be centrally mediated. Temporal summation (TS) of second pain and after-sensation are manifestations of central sensitization; therefore, this study explored these measures for better characterization of central pain processing in SOR. Twelve SOR adults and 12 healthy controls participated. TS was produced by a train of fifteen repetitive heat pulses, 0.7 s duration each, and 2 s of inter-stimulus interval, applied to the thenar-eminence, while four pain ratings were obtained. An after-sensation was then measured for 5 min, obtaining six pain ratings. No TS of pain was indicated in the SOR group (SOR: p = 0.36; control: p sensation, individuals with SOR continued to report pain for the duration of the 5 min measured (p = 0.002). These results demonstrate an atypical response pattern, suggesting alteration in pain processing and/or modulation at a central level in individuals with SOR. These possible neural changes may manifest themselves as interference with daily functioning as well as shed light on some of the between-subject variability seen in psychophysical testing in non-painful subjects.

  15. What colour is my arm? Changes in skin colour of an embodied virtual arm modulates pain threshold

    Directory of Open Access Journals (Sweden)

    Matteo eMartini

    2013-07-01

    Full Text Available It has been demonstrated that visual inputs can modulate pain. However, the influence of skin colour on pain perception is unknown. Red skin is associated to inflamed, hot and more sensitive skin while blue is associated to cold. We aimed to test whether the colour of the skin would alter the heat pain threshold. To this end, we used an immersive virtual environment where we induced embodiment of a virtual arm that was co-located with the real one and seen from a first person perspective. Virtual reality allowed us to dynamically modify the colour of the skin of the virtual arm. In order to test pain threshold, increasing ramps of heat stimulation applied on the participants’ arm were delivered concomitantly with the gradual intensification of different colours on the embodied avatar’s arm. We found that a reddened arm significantly decreased the pain threshold compared with normal and bluish coloured skin. This effect was specific when red was seen in the arm, while seeing red in a spot outside the arm did not decrease pain threshold. These results demonstrate an influence of skin colour on pain perception. This top-down modulation of pain through visual input suggests a potential use of embodied virtual bodies for pain therapy.

  16. Adaptations in responsiveness of brainstem pain-modulating neurons in acute compared to chronic inflammation

    Science.gov (United States)

    Cleary, Daniel R.; Heinricher, Mary M.

    2013-01-01

    Despite similar behavioral hypersensitivity, acute and chronic pain have distinct neural bases. Here we used intraplantar injection of Complete Freund’s Adjuvant (CFA) to directly compare activity of pain-modulating neurons in the rostral ventromedial medulla (RVM) in acute versus chronic inflammation. Heat- and von Frey-evoked withdrawal reflexes and corresponding RVM neuronal activity were recorded in lightly anesthetized animals either during the first hour after CFA injection (acute) or 3–10 days later (chronic). Thermal and modest mechanical hyperalgesia during acute inflammation were associated with increases in the spontaneous activity of pain-facilitating ON-cells and suppression of pain-inhibiting OFF-cells. Acute hyperalgesia was reversed by RVM block, showing that the increased activity of RVM ON-cells is necessary for acute behavioral hypersensitivity. In chronic inflammation, thermal hyperalgesia had resolved, but mechanical hyperalgesia had become pronounced. The spontaneous discharges of ON- and OFF-cells were not different from controls, but the mechanical response thresholds for both cell classes were reduced into the innocuous range. RVM block in the chronic condition worsened mechanical hyperalgesia. These studies identify distinct contributions of RVM ON- and OFF-cells to acute and chronic inflammatory hyperalgesia. During early immune-mediated inflammation, ON-cell spontaneous activity promotes hyperalgesia. After inflammation is established, the anti-nociceptive influence of OFF-cells is dominant, yet the lowered threshold for the OFF-cell pause allows behavioral responses to stimuli that would normally be considered innocuous. The efficacy of OFF-cells in counteracting sensitization of ascending transmission pathways could therefore be an important determining factor in development of chronic inflammatory pain. PMID:23588008

  17. Treatment for chronic low back pain: the focus should change to multimodal management that reflects the underlying pain mechanisms.

    Science.gov (United States)

    Müller-Schwefe, Gerhard; Morlion, Bart; Ahlbeck, Karsten; Alon, Eli; Coaccioli, Stefano; Coluzzi, Flaminia; Huygen, Frank; Jaksch, Wolfgang; Kalso, Eija; Kocot-Kępska, Magdalena; Kress, Hans-Georg; Mangas, Ana Cristina; Margarit Ferri, Cesar; Mavrocordatos, Philippe; Nicolaou, Andrew; Hernández, Concepción Pérez; Pergolizzi, Joseph; Schäfer, Michael; Sichère, Patrick

    2017-07-01

    Chronic low back pain: Chronic pain is the most common cause for people to utilize healthcare resources and has a considerable impact upon patients' lives. The most prevalent chronic pain condition is chronic low back pain (CLBP). CLBP may be nociceptive or neuropathic, or may incorporate both components. The presence of a neuropathic component is associated with more intense pain of longer duration, and a higher prevalence of co-morbidities. However, many physicians' knowledge of chronic pain mechanisms is currently limited and there are no universally accepted treatment guidelines, so the condition is not particularly well managed. Diagnosis should begin with a focused medical history and physical examination, to exclude serious spinal pathology that may require evaluation by an appropriate specialist. Most patients have non-specific CLBP, which cannot be attributed to a particular cause. It is important to try and establish whether a neuropathic component is present, by combining the findings of physical and neurological examinations with the patient's history. This may prove difficult, however, even when using screening instruments. Multimodal management: The multifactorial nature of CLBP indicates that the most logical treatment approach is multimodal: i.e. integrated multidisciplinary therapy with co-ordinated somatic and psychotherapeutic elements. As both nociceptive and neuropathic components may be present, combining analgesic agents with different mechanisms of action is a rational treatment modality. Individually tailored combination therapy can improve analgesia whilst reducing the doses of constituent agents, thereby lessening the incidence of side effects. This paper outlines the development of CLBP and the underlying mechanisms involved, as well as providing information on diagnosis and the use of a wide range of pharmaceutical agents in managing the condition (including NSAIDs, COX-2 inhibitors, tricyclic antidepressants, opioids and

  18. A comparative study of pain following endodontic treatment under general anesthesia

    Directory of Open Access Journals (Sweden)

    Feizi Ghader

    2015-01-01

    Full Text Available   Background and Aims: Postoperativee endodontic pain is an outstanding problem for dental patients. Therefore, a successful management of endodontic pain has become as one of the main dental objectives. The aim of the present study was to compare the postoperative endodontic pain in patients under general anesthesia versus local anesthesia.   Materials and Methods: For conducting this clinical trial study, 50 patients having mandibular molars candidate for root canal therapy were selected. Twenty-five patients treated under general anesthesia because of their fear, anxiety or gag reflex. Other 25 patients treated under local anesthesia. All teeth were prepared using engine-driven rotary system in a crown-down technique and filled using lateral condensation technique. Heft- parker visual analog scale was used to measure the degree of pain at 6, 12, 24, and 48 hours after the treatment. Mann-Whitney, Chi-square, and T-tests were used to compare the intensity of postoperative pain between the groups.   Results: The mean intensity of postoperative pain in local and general anesthesia groups at 6, 12 and 24 hours had statistically significant difference (P<0.05.   Conclusion: Postoperative pain in patients who treated under general anesthesia was significantly less than the patients who treated under local anesthesia.

  19. Nanomaterials modulate stem cell differentiation: biological interaction and underlying mechanisms.

    Science.gov (United States)

    Wei, Min; Li, Song; Le, Weidong

    2017-10-25

    Stem cells are unspecialized cells that have the potential for self-renewal and differentiation into more specialized cell types. The chemical and physical properties of surrounding microenvironment contribute to the growth and differentiation of stem cells and consequently play crucial roles in the regulation of stem cells' fate. Nanomaterials hold great promise in biological and biomedical fields owing to their unique properties, such as controllable particle size, facile synthesis, large surface-to-volume ratio, tunable surface chemistry, and biocompatibility. Over the recent years, accumulating evidence has shown that nanomaterials can facilitate stem cell proliferation and differentiation, and great effort is undertaken to explore their possible modulating manners and mechanisms on stem cell differentiation. In present review, we summarize recent progress in the regulating potential of various nanomaterials on stem cell differentiation and discuss the possible cell uptake, biological interaction and underlying mechanisms.

  20. Gum chewing modulates heart rate variability under noise stress.

    Science.gov (United States)

    Ekuni, Daisuke; Tomofuji, Takaaki; Takeuchi, Noriko; Morita, Manabu

    2012-12-01

    Gum chewing may relieve stress, although this hypothesis has not been proven. Heart-rate variability (HRV) is commonly used to measure stress levels. However, it is not known if gum chewing modulates HRV under acute stress. The aim of this study was to investigate the effects of gum chewing on HRV under acute stress. A cross-over study involving 47 non-smoking healthy subjects, aged 22-27 years, was carried out. The subjects received a stress procedure with gum chewing (GS group) and without gum chewing (S group). Additionally, the other 20 subjects were allocated to the gum chewing without stress group (G group). The GS and S groups were exposed to noise for 5 min (75 dBA) as stress. Before and after stress exposure/gum chewing, participants completed the state portion of the State-Trait Anxiety Inventory (STAI-s) and a single Stress Visual Analogue Scale (VAS) measurement. HRV measurement was performed before and during stress/gum chewing for 5 min. After the stress procedure, VAS score significantly increased in the GS and S groups. During the stress procedure, the GS group showed a significantly lower level of high frequency (HF) and higher levels of low frequency (LF) and LF/HF than the S group. However, there were no significant differences in the scores of the state portion of the State-Trait Anxiety Inventory (STAI-s) and VAS between the two stress groups. These findings suggest that gum chewing modulates HRV, but may not relieve acute stress caused by noise.

  1. Modulation of formalin-induced pain-related behaviour by clonidine and yohimbine in the Speke's hinged tortoise (Kiniskys spekii)

    DEFF Research Database (Denmark)

    Makau, C M; Towett, P K; Abelson, K S P

    2017-01-01

    The study was designed to investigate the involvement of noradrenergic and serotonergic receptor systems in the modulation of formalin-induced pain-related behaviour in the Speke's hinged tortoise. Intradermal injection of 100 μL of formalin at a dilution of 12.5% caused pain-related behaviour...... reduction in the duration of the formalin-induced pain-related behaviour. The effect of clonidine was reversed by intrathecal administration of yohimbine at a dose of 26.7 μg/kg. The effect of yohimbine at a dose of 50 μg/kg was reversed by intrathecal injection of 20 μg/kg of the serotonergic receptor...... in tortoises. The data also suggest that testudines have noradrenergic and serotonergic systems that appear to play a role in the modulation of pain in this species....

  2. 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

  3. Acute pain management: acetaminophen and ibuprofen are often under-dosed.

    Science.gov (United States)

    Milani, Gregorio P; Benini, Franca; Dell'Era, Laura; Silvagni, Davide; Podestà, Alberto F; Mancusi, Rossella Letizia; Fossali, Emilio F

    2017-07-01

    Most children with pain are managed by either acetaminophen or ibuprofen. However, no study has so far investigated if children are prescribed adequate doses of acetaminophen or ibuprofen in emergency department. Aim of this retrospective study was to investigate the prevalence of under-dosage of these drugs in children presenting with pain in emergency department. Children initially prescribed with acetaminophen or ibuprofen for pain management were included. The χ 2 automatic interaction detection method was used considering the percentage variation from the minimum of the appropriate dose as dependent variable while prescribed drug, age, gender, body weight, type of hospital (pediatric or general), and availability of internal guidelines on pediatric pain management in the emergency department as independent variables. Data on 1471 children managed for pain were available. Under-dosage was prescribed in 893 subjects (61%), of whom 577 were prescribed acetaminophen and 316 ibuprofen. The use of acetaminophen suppositories, body weight 40 kg, and the use of oral ibuprofen identified clusters of children associated with under-dosage prescription. Prescription of acetaminophen and ibuprofen was frequently under-dosed. The use of suppositories, lower and higher body weight, and the use of ibuprofen were associated with under-dosage. Under-dosing may reflect prescription of anti-pyretic doses. Agenzia Italiana del Farmaco-Observational Study Register (RSO). Registration code: PIERRE/1 What is Known: • Pain is frequent in children presented to emergency department. • International recommendations on pain management are often not implemented. What is New: • Acetaminophen and ibuprofen were frequently underdosed in children prescribed for pain in the Italian emergency departments. • Under-dosage may be related to the habit of using acetaminophen and ibuprofen in the recommended range for fever treatment.

  4. Relationship among perceived stress, anxiety, depression and craniocervical pain in nursing professionals under stress at work

    Directory of Open Access Journals (Sweden)

    Daniela Pozzebon

    Full Text Available Abstract Introduction: The appearance and evolution of some clinical pain conditions may be influenced by stress and other psychosocial factors. Face, head and cervical muscles may increase their activity and tension in the presence of stress, leading to craniocervicomandibular pain in individuals exposed to stress. Objective: To assess the relationship among perceived stress, anxiety, depression and craniocervicomandibular pain in nursing professionals under stress at work. Materials and Methods: Forty-three women under stress at work, according to the Job Stress Scale (JSS, were assessed by the Perceived Stress Scale (PSS, the Hospital Anxiety and Depression Scale (HADS, pressure pain threshold, measured by algometry, and muscle sensitivity to hand palpation of the masticatory and cervical muscles. Results: A low moderate level of perceived stress was found in 62.79% of the sample, anxiety in 11.63% and depression in 9.30%. The psychosocial scales correlated with each other. No correlation was found between pressure pain threshold and perceived stress, anxiety and depression. The level of pain to hand palpation correlated with the perceived stress scores. Conclusion: Pressure pain threshold was not influenced by the psychosocial factors assessed. Pain intensity to hand palpation, however, was higher as the perception of stress increased.

  5. The role of endogenous molecules in modulating pain through transient receptor potential vanilloid 1 (TRPV1).

    Science.gov (United States)

    Morales-Lázaro, Sara L; Simon, Sidney A; Rosenbaum, Tamara

    2013-07-01

    Pain is a physiological response to a noxious stimulus that decreases the quality of life of those sufferring from it. Research aimed at finding new therapeutic targets for the treatment of several maladies, including pain, has led to the discovery of numerous molecular regulators of ion channels in primary afferent nociceptive neurons. Among these receptors is TRPV1 (transient receptor potential vanilloid 1), a member of the TRP family of ion channels. TRPV1 is a calcium-permeable channel, which is activated or modulated by diverse exogenous noxious stimuli such as high temperatures, changes in pH, and irritant and pungent compounds, and by selected molecules released during tissue damage and inflammatory processes. During the last decade the number of endogenous regulators of TRPV1's activity has increased to include lipids that can negatively regulate TRPV1, as is the case for cholesterol and PIP2 (phosphatidylinositol 4,5-biphosphate) while, in contrast, other lipids produced in response to tissue injury and ischaemic processes are known to positively regulate TRPV1. Among the latter, lysophosphatidic acid activates TRPV1 while amines such as N-acyl-ethanolamines and N-acyl-dopamines can sensitize or directly activate TRPV1. It has also been found that nucleotides such as ATP act as mediators of chemically induced nociception and pain and gases, such as hydrogen sulphide and nitric oxide, lead to TRPV1 activation. Finally, the products of lipoxygenases and omega-3 fatty acids among other molecules, such as divalent cations, have also been shown to endogenously regulate TRPV1 activity. Here we provide a comprehensive review of endogenous small molecules that regulate the function of TRPV1. Acting through mechanisms that lead to sensitization and desensitization of TRPV1, these molecules regulate pathways involved in pain and nociception. Understanding how these compounds modify TRPV1 activity will allow us to comprehend how some pathologies are associated with

  6. Regeneration of spine disc and joint cartilages under temporal and space modulated laser radiation

    Science.gov (United States)

    Sobol, E.; Shekhter, A.; Baskov, A.; Baskov, V.; Baum, O.; Borchshenko, I.; Golubev, V.; Guller, A.; Kolyshev, I.; Omeltchenko, A.; Sviridov, A.; Zakharkina, O.

    2009-02-01

    The effect of laser radiation on the generation of hyaline cartilage in spine disc and joints has been demonstrated. The paper considers physical processes and mechanisms of laser regeneration, presents results of investigations aimed to optimize laser settings and to develop feedback control system for laser reconstruction of spine discs. Possible mechanisms of laser-induced regeneration include: (1) Space and temporary modulated laser beam induces nonhomogeneous and pulse repetitive thermal expansion and stress in the irradiated zone of cartilage. Mechanical effect due to controllable thermal expansion of the tissue and micro and nano gas bubbles formation in the course of the moderate (up to 45-50 oC) heating of the NP activate biological cells (chondrocytes) and promote cartilage regeneration. (2) Nondestructive laser radiation leads to the formation of nano and micro-pores in cartilage matrix. That promotes water permeability and increases the feeding of biological cells. Results provide the scientific and engineering basis for the novel low-invasive laser procedures to be used in orthopedics for the treatment cartilages of spine and joints. The technology and equipment for laser reconstruction of spine discs have been tested first on animals, and then in a clinical trial. Since 2001 the laser reconstruction of intervertebral discs have been performed for 340 patients with chronic symptoms of low back or neck pain who failed to improve with non-operative care. Substantial relief of back pain was obtained in 90% of patients treated who returned to their daily activities. The experiments on reparation of the defects in articular cartilage of the porcine joints under temporal and spase modulated laser radiation have shown promising results.

  7. Central terminal sensitization of TRPV1 by descending serotonergic facilitation modulates chronic pain.

    Science.gov (United States)

    Kim, Yu Shin; Chu, Yuxia; Han, Liang; Li, Man; Li, Zhe; LaVinka, Pamela Colleen; Sun, Shuohao; Tang, Zongxiang; Park, Kyoungsook; Caterina, Michael J; Ren, Ke; Dubner, Ronald; Wei, Feng; Dong, Xinzhong

    2014-02-19

    The peripheral terminals of primary nociceptive neurons play an essential role in pain detection mediated by membrane receptors like TRPV1, a molecular sensor of heat and capsaicin. However, the contribution of central terminal TRPV1 in the dorsal horn to chronic pain has not been investigated directly. Combining primary sensory neuron-specific GCaMP3 imaging with a trigeminal neuropathic pain model, we detected robust neuronal hyperactivity in injured and uninjured nerves in the skin, soma in trigeminal ganglion, and central terminals in the spinal trigeminal nucleus. Extensive TRPV1 hyperactivity was observed in central terminals innervating all dorsal horn laminae. The central terminal TRPV1 sensitization was maintained by descending serotonergic (5-HT) input from the brainstem. Central blockade of TRPV1 or 5-HT/5-HT3A receptors attenuated central terminal sensitization, excitatory primary afferent inputs, and mechanical hyperalgesia in the territories of injured and uninjured nerves. Our results reveal central mechanisms facilitating central terminal sensitization underlying chronic pain. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Event-related cortical processing in neuropathic pain under long-term spinal cord stimulation.

    Science.gov (United States)

    Weigel, Ralf; Capelle, H Holger; Flor, Herta; Krauss, Joachim K

    2015-01-01

    Several mechanisms were suggested in the past to explain the beneficial effect of spinal cord stimulation (SCS) in patients suffering from neuropathic pain. Little is known about potential supraspinal mechanisms. In this study cortical signaling of patients with neuropathic pain and successful long-term treatment with SCS was analyzed. Observational study. University hospital, neurosurgical department, outpatient clinic for movement disorders and pain, institute for cognitive and clinical neuroscience. Nine patients with neuropathic pain of a lower extremity with a lasting response to chronic SCS were included. Cortical activity was analyzed using event-related potentials of the electroencephalogram after non-painful and painful stimulation. Each patient was tested under the effect of long-term SCS and 24 hours after cessation of SCS. Cortical areas involved in the peaks of evoked potentials were localized using a source localization method based on a fixed dipole model. Detection threshold and intensity of non-painful stimulation did not differ significantly on both sides. Pain threshold was significantly lower on the neuropathic side under the effect of SCS (P = 0.03). Bilateral pain thresholds were significantly lower (P = 0.03 healthy side, P = 0.003 neuropathic side) in 5 patients with increased pain after cessation of SCS. Under the effect of SCS cortical negativities (N1, N2, N3) and positivities (P1) demonstrated bilaterally comparable amplitudes. After cessation of SCS, decreased threshold for peripheral stimulation resulted in lowered negativities on both sides. The positivity P1 was differentially regulated and was reduced more contralateral to the unaffected side. N2 was localized at the sensory representation of the leg within the homunculus. The main vector of P1 was localized within the cingular cortex (CC) and moved more anteriorly under the effect of SCS. The exact time span that SCS continues to have an effect is not known. However, due to patient

  9. A3 adenosine receptor agonist prevents the development of paclitaxel-induced neuropathic pain by modulating spinal glial-restricted redox-dependent signaling pathways.

    Science.gov (United States)

    Janes, Kali; Esposito, Emanuela; Doyle, Timothy; Cuzzocrea, Salvatore; Tosh, Dillip K; Jacobson, Kenneth A; Salvemini, Daniela

    2014-12-01

    Chemotherapy-induced peripheral neuropathy accompanied by chronic neuropathic pain is the major dose-limiting toxicity of several anticancer agents including the taxane paclitaxel (Taxol). A critical mechanism underlying paclitaxel-induced neuropathic pain is the increased production of peroxynitrite in spinal cord generated in response to activation of the superoxide-generating enzyme, NADPH oxidase. Peroxynitrite in turn contributes to the development of neuropathic pain by modulating several redox-dependent events in spinal cord. We recently reported that activation of the Gi/Gq-coupled A3 adenosine receptor (A3AR) with selective A3AR agonists (ie, IB-MECA) blocked the development of chemotherapy induced-neuropathic pain evoked by distinct agents, including paclitaxel, without interfering with anticancer effects. The mechanism or mechanisms of action underlying these beneficial effects has yet to be explored. We now demonstrate that IB-MECA attenuates the development of paclitaxel-induced neuropathic pain by inhibiting the activation of spinal NADPH oxidase and two downstream redox-dependent systems. The first relies on inhibition of the redox-sensitive transcription factor (NFκB) and mitogen activated protein kinases (ERK and p38) resulting in decreased production of neuroexcitatory/proinflammatory cytokines (TNF-α, IL-1β) and increased formation of the neuroprotective/anti-inflammatory IL-10. The second involves inhibition of redox-mediated posttranslational tyrosine nitration and modification (inactivation) of glia-restricted proteins known to play key roles in regulating synaptic glutamate homeostasis: the glutamate transporter GLT-1 and glutamine synthetase. Our results unravel a mechanistic link into biomolecular signaling pathways employed by A3AR activation in neuropathic pain while providing the foundation to consider use of A3AR agonists as therapeutic agents in patients with chemotherapy-induced peripheral neuropathy. Copyright © 2014

  10. Peripheral Galanin Receptor 2 as a Target for the Modulation of Pain

    Directory of Open Access Journals (Sweden)

    Richard P. Hulse

    2012-01-01

    Full Text Available The neuropeptide galanin is widely expressed in the nervous system and has an important role in nociception. It has been shown that galanin can facilitate and inhibit nociception in a dose-dependent manner, principally through the central nervous system, with enhanced antinociceptive actions after nerve injury. However, following nerve injury, expression of galanin within the peripheral nervous system is dramatically increased up to 120-fold. Despite this striking increase in the peripheral nervous system, few studies have investigated the role that galanin plays in modulating nociception at the primary afferent nociceptor. Here, we summarise the recent work supporting the role of peripherally expressed galanin with particular reference to the dual actions of the galanin receptor 2 in neuropathic pain highlighting this as a potential target analgesic.

  11. Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1

    Directory of Open Access Journals (Sweden)

    Yelena Nersesyan

    2017-11-01

    Full Text Available Oxytocin is a hormone with various actions. Oxytocin-containing parvocellular neurons project to the brainstem and spinal cord. Oxytocin release from these neurons suppresses nociception of inflammatory pain, the molecular mechanism of which remains unclear. Here, we report that the noxious stimulus receptor TRPV1 is an ionotropic oxytocin receptor. Oxytocin elicits TRPV1 activity in native and heterologous expression systems, regardless of the presence of the classical oxytocin receptor. In TRPV1 knockout mice, DRG neurons exhibit reduced oxytocin sensitivity relative to controls, and oxytocin injections significantly attenuate capsaicin-induced nociception in in vivo experiments. Furthermore, oxytocin potentiates TRPV1 in planar lipid bilayers, supporting a direct agonistic action. Molecular modeling and simulation experiments provide insight into oxytocin-TRPV1 interactions, which resemble DkTx. Together, our findings suggest the existence of endogenous regulatory pathways that modulate nociception via direct action of oxytocin on TRPV1, implying its analgesic effect via channel desensitization.

  12. Oxytocin in the periaqueductal gray participates in pain modulation in the rat by influencing endogenous opiate peptides.

    Science.gov (United States)

    Yang, Jun; Liang, Jin-Ying; Li, Peng; Pan, Yan-Juan; Qiu, Pei-Yong; Zhang, Jing; Hao, Fang; Wang, Da-Xin

    2011-06-01

    Periaqueductal gray (PAG) plays a very important role in pain modulation through endogenous opiate peptides including leucine-enkephalin (L-Ek), methionine-enkephalin (M-Ek), β-endorphin (β-Ep) and dynorphin A(1-13) (DynA(1-13)). Our pervious study has demonstrated that intra-PAG injection of oxytocin (OXT) increases the pain threshold, and local administration of OXT receptor antagonist decreases the pain threshold, in which the antinociceptive role of OXT can be reversed by pre-PAG administration of OXT receptor antagonist. The experiment was designed to investigate the effect of OXT on endogenous opiate peptides in the rat PAG during the pain process. The results showed that (1) the concentrations of OXT, L-Ek, M-Ek and β-Ep, not DynA(1-13) in the PAG perfusion liquid were increased after the pain stimulation; (2) the concentrations of L-Ek, M-Ek and β-Ep, not DynA(1-13) in the PAG perfusion liquid were decreased by the OXT receptor antagonist; (3) the increased pain threshold induced by the OXT was attenuated by naloxone, an opiate receptor antagonist; and (4) the concentrations of L-Ek, M-Ek and β-Ep, not DynA(1-13) in the PAG perfusion liquid were increased by exogenous OXT administration. The data suggested that OXT in the PAG could influence the L-Ek, M-Ek and β-Ep rather than DynA(1-13) to participate in pain modulation, i.e. OXT in the PAG participate in pain modulation by influencing the L-Ek, M-Ek and β-Ep rather than DynA(1-13). Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Opioid modulation of facial itch- and pain-related responses and grooming behavior in rats.

    Science.gov (United States)

    Spradley, Jessica M; Davoodi, Auva; Carstens, Mirela Iodi; Carstens, Earl

    2012-09-01

    Intradermal facial injections of pruritogens or algogens elicit distinct behavioral hindlimb scratch or forelimb wiping responses in rodents. We systematically investigated the parameters and opioid modulation of these evoked behaviors and spontaneous facial grooming in rats. Serotonin (5-HT) elicited hindlimb scratch bouts with few wipes. Scratching was attenuated by the µ-opiate antagonist naltrexone but not morphine. In contrast, cheek injection of mustard oil (allyl-isothiocyanate (AITC)) elicited ipsilateral forelimb wipes but little hindlimb scratching. AITC-evoked wiping was significantly attenuated by morphine but not naltrexone. Spontaneous facial grooming by the forepaws was attenuated by naltrexone, whereas morphine did not affect grooming behavior before or after cheek injections of 5-HT or AITC. These data validate that the rodent "cheek" model discriminates between itch- and pain-related behaviors. Naltrexone sensitivity of facial grooming and 5-HT-evoked scratch-ing suggests a common functionality. Forelimb wipes may represent a nocifensive response akin to rubbing an injury to relieve pain.

  14. Spinal translocator protein (TSPO) modulates pain behavior in rats with CFA-induced monoarthritis.

    Science.gov (United States)

    Hernstadt, Hayley; Wang, Shuxing; Lim, Grewo; Mao, Jianren

    2009-08-25

    Translocator protein 18 kDa (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), is predominantly located in the mitochondrial outer membrane and plays an important role in steroidogenesis, immunomodulation, cell survival and proliferation. Previous studies have shown an increased expression of TSPO centrally in neuropathology, as well as in injured nerves. TSPO has also been implicated in modulation of nociception. In the present study, we examined the hypothesis that TSPO is involved in the initiation and maintenance of inflammatory pain using a rat model of Complete Freund's Adjuvant (CFA)-induced monoarthritis of the tibio-tarsal joint. Immunohistochemistry was performed using Iba-1 (microglia), NeuN (neurons), anti-Glial Fibrillary Acidic Protein, GFAP (astrocytes) and anti-PBR (TSPO) on Days 1, 7 and 14 after CFA-induced arthritis. Rats with CFA-induced monoarthritis showed mechanical allodynia and thermal hyperalgesia on the ipsilateral hindpaw, which correlated with the increased TSPO expression in ipsilateral laminae I-II on all experimental days. Iba-1 expression in the ipsilateral dorsal horn was also increased on Days 7 and 14. Moreover, TSPO was colocalized with Iba-1, GFAP and NeuN within the spinal cord dorsal horn. The TSPO agonist Ro5-4864, given intrathecally, dose-dependently retarded or prevented the development of mechanical allodynia and thermal hyperalgesia in rats with CFA-induced monoarthritis. These findings provide evidence that spinal TSPO is involved in the development and maintenance of inflammatory pain behaviors in rats. Thus, spinal TSPO may present a central target as a complementary therapy to reduce inflammatory pain.

  15. The long-term impact of tissue injury on pain processing and modulation: a study on ex-prisoners of war who underwent torture.

    Science.gov (United States)

    Defrin, R; Ginzburg, K; Mikulincer, M; Solomon, Z

    2014-04-01

    Tissue injury may, in some instances, induce chronic pain lasting for decades. Torture survivors suffer from high rates of chronic pain and hypersensitivity in the previously injured regions. Whether torture survivors display generalized alterations in pain perception and modulation, and whether such alterations underlie their chronic pain is unknown. We aimed at exploring the long-term alterations in pain perception and modulation in torture survivors. In order to address these questions, a systematic quantitative somatosensory evaluation was performed in individuals (n = 60) who suffer from chronic pain, and who, decades previously, were tortured, resulting in substantial tissue damage. These individuals were compared with age- and sex-matched individuals (n = 44) of similar background. Testing included the measurement of pain threshold and pain tolerance, perceived suprathreshold stimuli, conditioned pain modulation (CPM) and temporal summation of pain (TSP) in intact body regions. Chronic pain was found highly prevalent (86.6%) among torture survivors, who exhibited higher suprathreshold pain ratings (p < 0.05), poorer CPM (p < 0.0001) and stronger TSP (p < 0.0001) than controls. Significant differences in CPM and TSP were also found between torture survivors and controls with chronic pain. Chronic pain intensity among torture survivors correlated negatively with the magnitude of CPM (r = -0.47, p < 0.01). Torture appears to induce generalized dysfunctional pain modulation that may underlie the intense chronic pain experienced by torture survivors decades after torture. The results may be generalized to instances where chronic pain exists for decades after severe injury in non-tortured populations and emphasize the importance of preventive care. © 2013 European Pain Federation - EFIC®

  16. State anxiety and depression as factors modulating and influencing postoperative pain in dental implant surgery. A prospective clinical survey

    Science.gov (United States)

    Gómez-de Diego, Rafael; Cutando-Soriano, Antonio; Montero-Martín, Javier; Prados-Frutos, Juan C.

    2014-01-01

    Objetives: To determine whether preoperative state anxiety and depression modulate or influence objective and subjective postoperative pain following dental implant insertion. Study Design: Prospective, clinical study with 7-day follow-up of a sample of 105 subjects who preoperatively completed the state anxiety questionnaire (STAI-E) and Beck Depression Inventory (BDI) and postoperatively, at 2 and 7 days, recorded objective pain with the Semmes-Weinstein mechanical esthesiometer (SW test) and subjective pain with the Visual Analog Scale (VAS). Results: 85.6% and 81.5% of patients, respectively, recorded no signs of state anxiety or depression. The correlation between anxiety and depression for both maxillary bones was the lower (P=0.02). The correlation between subjective and objective pain at 2 and 7 days, and the anatomic regions intervened, was statistically significant in the mandible at day 7 (P<0.01), and highly significant (P<0.001) for the other variables. The correlation between state anxiety and objective pain at day 7 was nearly statistically significant (P=0.07). Conclusions: The correlation between state anxiety and depression, and objective and subjective pain at day 7 was not statistically significant. A strong correlation was found between objective and subjective pain in the immediate postoperative period. Key words:Anxiety, depression, postoperative pain, dental implants. PMID:24880447

  17. SR-16234, a Novel Selective Estrogen Receptor Modulator for Pain Symptoms with Endometriosis: An Open-label Clinical Trial.

    Science.gov (United States)

    Harada, Tasuku; Ohta, Ikuko; Endo, Yusuke; Sunada, Hiroshi; Noma, Hisashi; Taniguchi, Fuminori

    2017-12-01

    SR-16234 is a selective estrogen receptor modulator (SERM) structurally different from approved SERM and has been reported to have estrogen receptor (ER) α antagonistic activity and strong affinity with a weak partial agonistic activity to ERβ receptor. SR-16234 showed strong inhibitory effects on transplanted endometrial cysts in the endometriosis model of rat and mouse. In this clinical trial, efficacy and safety of SR-16234 have been evaluated in endometriosis patients. This trial was an open-label single arm clinical trial. Ten patients with dysmenorrhea and pelvic pain associated with endometriosis and adenomyosis were enrolled in this trial, and received 40 mg of SR-16234 once daily for 12 weeks. The primary endpoint was the visual analogue scale (VAS) of pelvic pain. The secondary endpoints included dysmenorrhea score, pelvic pain score, objective observations (stiffness of Douglas' pouch, limitation of uterine movement, size of ovarian chocolate cysts, thickness of endometrium, and serum CA125 concentration) and safety. After oral administration of SR-16234 40 mg for 12 weeks, there were statistically significant decreases in pelvic pain VAS, total pelvic pain score, total dysmenorrhea score, stiffness of Douglas' pouch, limitation of uterine movement compared with the baseline values. The present trial suggested that a selective estrogen receptor modulator could be used for treatment of pain associated with endometriosis for the first time.

  18. Light induced modulation instability of surfaces under intense illumination

    KAUST Repository

    Burlakov, V. M.

    2013-12-17

    We show that a flat surface of a polymer in rubber state illuminated with intense electromagnetic radiation is unstable with respect to periodic modulation. Initial periodic perturbation is amplified due to periodic thermal expansion of the material heated by radiation. Periodic heating is due to focusing-defocusing effects caused by the initial surface modulation. The surface modulation has a period longer than the excitation wavelength and does not require coherent light source. Therefore, it is not related to the well-known laser induced periodic structures on polymer surfaces but may contribute to their formation and to other phenomena of light-matter interaction.

  19. Foraging traits modulate stingless bee community disassembly under forest loss.

    Science.gov (United States)

    Lichtenberg, Elinor M; Mendenhall, Chase D; Brosi, Berry

    2017-10-01

    Anthropogenic land use change is an important driver of impacts to biological communities and the ecosystem services they provide. Pollination is one ecosystem service that may be threatened by community disassembly. Relatively little is known about changes in bee community composition in the tropics, where pollination limitation is most severe and land use change is rapid. Understanding how anthropogenic changes alter community composition and functioning has been hampered by high variability in responses of individual species. Trait-based approaches, however, are emerging as a potential method for understanding responses of ecologically similar species to global change. We studied how communities of tropical, eusocial stingless bees (Apidae: Meliponini) disassemble when forest is lost. These bees are vital tropical pollinators that exhibit high trait diversity, but are under considerable threat from human activities. We compared functional traits of stingless bee species found in pastures surrounded by differing amounts of forest in an extensively deforested landscape in southern Costa Rica. Our results suggest that foraging traits modulate competitive interactions that underlie community disassembly patterns. In contrast to both theoretical predictions and temperate bee communities, we found that stingless bee species with the widest diet breadths were less likely to persist in sites with less forest. These wide-diet-breadth species also tend to be solitary foragers, and are competitively subordinate to group-foraging stingless bee species. Thus, displacement by dominant, group-foraging species may make subordinate species more dependent on the larger or more diversified resource pool that natural habitats offer. We also found that traits that may reduce reliance on trees-nesting in the ground or inside nests of other species-correlated with persistence in highly deforested landscapes. The functional trait perspective we employed enabled capturing community

  20. Stress Response Modulation Underlying the Psychobiology of Resilience.

    Science.gov (United States)

    Averill, Lynnette A; Averill, Christopher L; Kelmendi, Benjamin; Abdallah, Chadi G; Southwick, Steven M

    2018-03-28

    This review focuses on the relationship between resilience and the ability to effectively modulate the stress response. Neurobiological and behavioral responses to stress are highly variable. Exposure to a similar stressor can lead to heterogeneous outcomes-manifesting psychopathology in one individual, but having minimal effect, or even enhancing resilience, in another. We highlight aspects of stress response modulation related to early life development and epigenetics, selected neurobiological and neurochemical systems, and a number of emotional, cognitive, psychosocial, and behavioral factors important in resilience. We also briefly discuss interventions with potential to build and promote resilience. Throughout this review, we include evidence from recent preclinical and clinical studies relevant to the psychobiology of resilient stress response modulation. Effective modulation of the stress response is an essential component of resilience and is dependent on a complex interplay of neurobiological and behavioral factors.

  1. Conditioned Pain Modulation and Pressure Pain Sensitivity in the Adult Danish General Population: The DanFunD Study

    DEFF Research Database (Denmark)

    Skovbjerg, Sine; Jørgensen, Torben; Arendt-Nielsen, Lars

    2017-01-01

    was associated with lower PPTs (P body mass index and sex. CPM potency was lower in female compared with male participants (P ≤ .003), whereas no association with age was found. Higher level of education (P ≤ .05), premature withdrawal from the cold pressor test...... with cold pressor pain (hand) for 2 minutes. Conditioning pain intensity was assessed using a visual analog scale and questionnaire data were collected. Female sex (P body sites. For the trapezius muscle, high perceived stress...

  2. An investigation into the analgesic effects of different frequencies of the amplitude-modulated wave of interferential current therapy on cold-induced pain in normal subjects.

    Science.gov (United States)

    Johnson, Mark I; Tabasam, Ghazala

    2003-09-01

    To investigate the analgesic effects of different amplitude-modulated frequencies of interferential current therapy (IFT) on cold-induced pain in healthy subjects. Single-blind parallel group methodology was used. Subjects completed 6 cycles of the cold-induced pain test (2 pretreatment, 2 during treatment, 2 posttreatment). During each cycle, subjects plunged their hand into iced water and the time taken to reach pain threshold was recorded. The hand remained immersed in the iced water for a further 30 seconds, after which the self-reports of pain intensity and pain unpleasantness were recorded. Laboratory in the United Kingdom. Sixty unpaid, pain-free volunteers without a known pathology that could cause pain. IFT delivered on the nondominant arm at a "strong but comfortable" intensity without visible muscle twitches, using a quadripolar application technique at 1 of 6 possible amplitude modulated "beat" frequencies (20, 60, 100, 140, 180, 220Hz). The percentage change in pain threshold, pain intensity, and pain unpleasantness from the pretreatment baseline. Two-way repeated-measures analyses of variance found no effects for groups for pain threshold (P=.11) or pain ratings (P>.05). There were no effects for cycle for any of the outcome measures. Effects for group by cycle interaction were noted for pain intensity and unpleasantness ratings (P<.05), although post hoc analysis failed to determine the nature of this interaction. Experimentally induced cold pain was not influenced by IFT frequencies.

  3. Ageing monitoring in IGBT module under sinusoidal loading

    DEFF Research Database (Denmark)

    Ghimire, Pramod; Pedersen, Kristian Bonderup; Rannestad, Bjørn

    2015-01-01

    until failure. The characterization at different stages of lifetime indicates that the rise in resistance originates from thermo-mechanical degradation of interconnects. Post-test investigations: four-point probing and micro-sectioning indicate thermo-mechanical induced degradation of the chip topside...... different ways: calibration of power modules after 24 h of operation, offline characterization every 5 min of operation, and continuous measurement during normal converter operation. Four power modules are tested, which are cycled to different degradation levels by number of cycles, where one is tested......This paper presents monitoring of ageing in high power insulated gate bipolar transistor (IGBT) modules subjected to sinusoidal loading at nominal power level. On-state voltage for IGBT, diode, and rise in interconnection resistance are used as ageing parameters. These are measured in three...

  4. Chronic whiplash and central sensitization; an evaluation of the role of a myofascial trigger points in pain modulation

    Directory of Open Access Journals (Sweden)

    Freeman Michael D

    2009-04-01

    Full Text Available Abstract Objective it has been established that chronic neck pain following whiplash is associated with the phenomenon of central sensitization, in which injured and uninjured parts of the body exhibit lowered pain thresholds due to an alteration in central pain processing. it has furthermore been hypothesized that peripheral sources of nociception in the muscles may perpetuate central sensitization in chronic whiplash. the hypothesis explored in the present study was whether myofascial trigger points serve as a modulator of central sensitization in subjects with chronic neck pain. Design controlled case series. Setting outpatient chronic pain clinic. Subjects seventeen patients with chronic and intractable neck pain and 10 healthy controls without complaints of neck pain. Intervention symptomatic subjects received anesthetic infiltration of myofascial trigger points in the upper trapezius muscles and controls received the anesthetic in the thigh. Outcome measures: pre and post injection cervical range of motion, pressure pain thresholds (ppt over the infraspinatus, wrist extensor, and tibialis anterior muscles. sensitivity to light (photophobia and subjects' perception of pain using a visual analog scale (vas were also evaluated before and after injections. only the ppt was evaluated in the asymptomatic controls. Results immediate (within 1 minute alterations in cervical range of motion and pressure pain thresholds were observed following an average of 3.8 injections with 1–2 cc of 1% lidocaine into carefully identified trigger points. cervical range of motion increased by an average of 49% (p = 0.000 in flexion and 44% (p = 0.001 in extension, 47% (p = 0.000 and 28% (p Conclusion the present data suggest that myofascial trigger points serve to perpetuate lowered pain thresholds in uninjured tissues. additionally, it appears that lowered pain thresholds associated with central sensitization can be immediately reversed, even when associated

  5. PKMζ is essential for spinal plasticity underlying the maintenance of persistent pain

    Directory of Open Access Journals (Sweden)

    Laferrière Andre

    2011-12-01

    Full Text Available Abstract Background Chronic pain occurs when normally protective acute pain becomes pathologically persistent. We examined here whether an isoform of protein kinase C (PKC, PKMζ, that underlies long-term memory storage in various brain regions, also sustains nociceptive plasticity in spinal cord dorsal horn (SCDH mediating persistent pain. Results Cutaneous injury or spinal stimulation produced persistent increases of PKMζ, but not other atypical PKCs in SCDH. Inhibiting spinal PKMζ, but not full-length PKCs, reversed plasticity-dependent persistent painful responses to hind paw formalin and secondary mechanical hypersensitivity and SCDH neuron sensitization after hind paw capsaicin, without affecting peripheral sensitization-dependent primary heat hypersensitivity after hind paw capsaicin. Inhibiting spinal PKMζ, but not full-length PKCs, also reversed mechanical hypersensitivity in the rat hind paw induced by spinal stimulation with intrathecal dihydroxyphenylglycine. Spinal PKMζ inhibition also alleviated allodynia 3 weeks after ischemic injury in rats with chronic post-ischemia pain (CPIP, at a point when allodynia depends on spinal changes. In contrast, spinal PKMζ inhibition did not affect allodynia in rats with chronic contriction injury (CCI of the sciatic nerve, or CPIP rats early after ischemic injury, when allodynia depends on ongoing peripheral inputs. Conclusions These results suggest spinal PKMζ is essential for the maintenance of persistent pain by sustaining spinal nociceptive plasticity.

  6. Pisotriquetral joint disorders: an under-recognized cause of ulnar side wrist pain

    Energy Technology Data Exchange (ETDEWEB)

    Moraux, A. [Hopital Roger Salengro, Service d' Imagerie Musculo-Squelettique, Centre de Consultation de l' Appareil Locomoteur, CHRU Lille (France); Imagerie Medicale Jacquemars Gielee, Lille (France); Lefebvre, G.; Pansini, V.; Aucourt, J.; Vandenbussche, L.; Cotten, A. [Hopital Roger Salengro, Service d' Imagerie Musculo-Squelettique, Centre de Consultation de l' Appareil Locomoteur, CHRU Lille (France); Demondion, X. [Hopital Roger Salengro, Service d' Imagerie Musculo-Squelettique, Centre de Consultation de l' Appareil Locomoteur, CHRU Lille (France); Pole Recherche Faculte de Medecine de Lille, Laboratoire d' Anatomie, Lille (France)

    2014-06-15

    Pisotriquetral joint disorders are often under-recognized in routine clinical practice. They nevertheless represent a significant cause of ulnar side wrist pain. The aim of this article is to present the main disorders of this joint and discuss the different imaging modalities that can be useful for its assessment. (orig.)

  7. Seeing One's Own Painful Hand Positioned in the Contralateral Space Reduces Subjective Reports of Pain and Modulates Laser Evoked Potentials.

    Science.gov (United States)

    Valentini, Elia; Koch, Katharina; Aglioti, Salvatore Maria

    2015-06-01

    Studies report that viewing the body or keeping one's arms crossed while receiving painful stimuli may have an analgesic effect. Interestingly, changes in ratings of pain are accompanied by a reduction of brain metabolism or of laser evoked potentials amplitude. What remains unknown is the link between visual analgesia and crossed-arms related analgesia. Here, we investigated pain perception and laser evoked potentials in 3 visual contexts while participants kept their arms in a crossed or uncrossed position during vision of 1) one's own hand, 2) a neutral object in the same spatial location, and 3) a fixation cross placed in front of the participant. We found that having vision of the affected body part in the crossed-arms position was associated with a significant reduction in pain reports. However, no analgesic effect of having vision of the hand in an uncrossed position or of crossing the arms alone was found. The increase of the late vertex laser evoked potential P2 amplitude indexed a general effect of vision of the hand. Our results hint at a complex interaction between cross-modal input and body representation in different spatial frames of reference and at the same time question the effect of visual analgesia and crossed-arms analgesia alone. We found that nociceptive stimuli delivered to the hand in a crossed-arms position evoke less pain than in a canonical anatomic position. Yet we report no significant analgesic effect of vision or crossing the arms on their own. These findings foster the integration of visuospatial and proprioceptive information in rehabilitation protocols. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  8. Pain modulation is affected differently in medication-overuse headache and chronic myofascial pain - A multimodal MRI study.

    Science.gov (United States)

    Michels, Lars; Christidi, Foteini; Steiger, Vivian R; Sándor, Peter S; Gantenbein, Andreas R; Landmann, Gunther; Schreglmann, Sebastian R; Kollias, Spyros; Riederer, Franz

    2017-07-01

    Background Neuroimaging studies revealed structural and functional changes in medication-overuse headache (MOH), but it remains unclear whether similar changes could be observed in other chronic pain disorders. Methods In this cross-sectional study, we investigated functional connectivity (FC) with resting-state functional magnetic resonance imaging (fMRI) and white matter integrity using diffusion tensor imaging (DTI) to measure fractional anisotropy (FA) and mean diffusivity (MD) in patients with MOH ( N = 12) relative to two control groups: patients with chronic myofascial pain (MYO; N = 11) and healthy controls (CN; N = 16). Results In a data-driven approach we found hypoconnectivity in the fronto-parietal attention network in both pain groups relative to CN (i.e. MOH < CN and MYO < CN). In contrast, hyperconnectivity in the saliency network (SN) was detected only in MOH, which correlated with FA in the insula. In a seed-based analysis we investigated FC between the periaqueductal grey (PAG) and all other brain regions. In addition to overlapping hyperconnectivity seen in patient groups (relative to CN), MOH had a distinct connectivity pattern with lower FC to parieto-occipital regions and higher FC to orbitofrontal regions compared to controls. FA and MD abnormalities were mostly observed in MOH, involving the insula. Conclusions Hyperconnectivity within the SN along with associated white matter changes therein suggest a particular role of this network in MOH. In addition, abnormal connectivity between the PAG and other pain modulatory (frontal) regions in MOH are consistent with dysfunctional central pain control.

  9. Peroxisome Proliferator-Activated Receptor Agonists Modulate Neuropathic Pain: a Link to Chemokines?

    Directory of Open Access Journals (Sweden)

    Caroline eFreitag

    2014-08-01

    Full Text Available Chronic pain presents a widespread and intractable medical problem. While numerous pharmaceuticals are used to treat chronic pain, drugs that are safe for extended use and highly effective at treating the most severe pain do not yet exist. Chronic pain resulting from nervous system injury (neuropathic pain is common in conditions ranging from multiple sclerosis to HIV-1 infection to type II diabetes. Inflammation caused by neuropathy is believed to contribute to the generation and maintenance of neuropathic pain. Chemokines are key inflammatory mediators, several of which (MCP-1, RANTES, MIP-1α, fractalkine, SDF-1 among others have been linked to chronic, neuropathic pain in both human conditions and animal models. The important roles chemokines play in inflammation and pain make them an attractive therapeutic target. Peroxisome proliferator-activated receptors are a family of nuclear receptors known for their roles in metabolism. Recent research has revealed that PPARs also play a role in inflammatory gene repression. PPAR agonists have wide-ranging effects including inhibition of chemokine expression and pain behavior reduction in animal models. Experimental evidence suggests a connection between PPAR agonists' pain ameliorating effects and suppression of inflammatory gene expression, including chemokines. In early clinical research, one PPARα agonist, palmitoylethanolamide, shows promise in relieving chronic pain. If this link can be better established, PPAR agonists may represent a new drug therapy for neuropathic pain.

  10. Modulation of formalin-induced pain-related behaviour by clonidine and yohimbine in the Speke's hinged tortoise (Kiniskys spekii).

    Science.gov (United States)

    Makau, C M; Towett, P K; Abelson, K S P; Kanui, T I

    2017-10-01

    The study was designed to investigate the involvement of noradrenergic and serotonergic receptor systems in the modulation of formalin-induced pain-related behaviour in the Speke's hinged tortoise. Intradermal injection of 100 μL of formalin at a dilution of 12.5% caused pain-related behaviour (hindlimb withdrawal) that lasted for a mean time of 19.28 min (monophasic response). Intrathecal administration of clonidine (α 2 -adrenergic receptor agonist) and yohimbine (α 2 -adrenergic receptor antagonist) at a dose of 40 μg/kg and 37.5 μg/kg or 50 μg/kg, respectively, caused a highly significant reduction in the duration of the formalin-induced pain-related behaviour. The effect of clonidine was reversed by intrathecal administration of yohimbine at a dose of 26.7 μg/kg. The effect of yohimbine at a dose of 50 μg/kg was reversed by intrathecal injection of 20 μg/kg of the serotonergic receptor antagonist methysergide maleate. When performing antagonistic reactions, the administration of the antagonist was followed immediately by that of the agonist. The study indicates that for experimental purposes, intrathecal route of drug administration through the atlanto-occipital joint is effective in tortoises. The data also suggest that testudines have noradrenergic and serotonergic systems that appear to play a role in the modulation of pain in this species. © 2016 John Wiley & Sons Ltd.

  11. Performance Investigation of Air Velocity Effects on PV Modules under Controlled Conditions

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    Muzaffar Ali

    2017-01-01

    Full Text Available Junction temperature of PV modules is one of the key parameters on which the performance of PV modules depends. In the present work, an experimental investigation was carried out to analyze the effects of air velocity on the performance of two PV modules, that is, monocrystalline silicon and polycrystalline silicon under the controlled conditions of a wind tunnel in the presence of an artificial solar simulator. The parameters investigated include the surface temperature variation, power output, and efficiency of PV modules under varying air velocity from near zero (indoor lab. conditions to 15 m/s. Additionally, the results were also determined at two different module angular positions: at 0° angle, that is, parallel to air direction and at 10° angle with the direction of coming air to consider the effects of tilt angles. Afterwards, the thermal analysis of the modules was performed using Ansys-Fluent in which junction temperature and heat flux of modules were determined by applying appropriate boundary conditions, such as air velocity, heat flux, and solar radiation. Finally, the numerical results are compared with the experiment in terms of junction temperatures of modules and good agreement was found. Additionally, the results showed that the maximum module temperature drops by 17.2°C and the module efficiency and power output increased from 10 to 12% with increasing air velocity.

  12. Central sensitization as the mechanism underlying pain in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

    Science.gov (United States)

    Di Stefano, G; Celletti, C; Baron, R; Castori, M; Di Franco, M; La Cesa, S; Leone, C; Pepe, A; Cruccu, G; Truini, A; Camerota, F

    2016-09-01

    Patients with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT) commonly suffer from pain. How this hereditary connective tissue disorder causes pain remains unclear although previous studies suggested it shares similar mechanisms with neuropathic pain and fibromyalgia. In this prospective study seeking information on the mechanisms underlying pain in patients with JHS/EDS-HT, we enrolled 27 consecutive patients with this connective tissue disorder. Patients underwent a detailed clinical examination, including the neuropathic pain questionnaire DN4 and the fibromyalgia rapid screening tool. As quantitative sensory testing methods, we included thermal-pain perceptive thresholds and the wind-up ratio and recorded a standard nerve conduction study to assess non-nociceptive fibres and laser-evoked potentials, assessing nociceptive fibres. Clinical examination and diagnostic tests disclosed no somatosensory nervous system damage. Conversely, most patients suffered from widespread pain, the fibromyalgia rapid screening tool elicited positive findings, and quantitative sensory testing showed lowered cold and heat pain thresholds and an increased wind-up ratio. While the lack of somatosensory nervous system damage is incompatible with neuropathic pain as the mechanism underlying pain in JHS/EDS-HT, the lowered cold and heat pain thresholds and increased wind-up ratio imply that pain in JHS/EDS-HT might arise through central sensitization. Hence, this connective tissue disorder and fibromyalgia share similar pain mechanisms. WHAT DOES THIS STUDY ADD?: In patients with JHS/EDS-HT, the persistent nociceptive input due to joint abnormalities probably triggers central sensitization in the dorsal horn neurons and causes widespread pain. © 2016 European Pain Federation - EFIC®

  13. Effect of sport massage on pressure pain threshold and tolerance in athletes under eccentric exercise

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    Abdullah Selim KAPLAN

    2014-08-01

    Full Text Available Extensive line of evidence suggest that pain threshold and tolerance alters following exercise, although the mechanisms have not been elucidated yet. In this st udy, we investigated the role of sport massage on pressure pain threshold and tolerance in athletes under eccentric exercise. Ten male athletes aged 23 ± 1 years with 9.67 ± 3.04 years of athletic training were recruited for this study . Following baseline measurements of pressure pain threshold and tolerance from m. biceps brachii and m. triceps brachii muscle and myofascial regions of the dominant upper extremity by using a digital algometer, subjects were underwent an acute bout of eccentric exercise. Par ticipants were completed 4 sets of eccentric exercise each comprising 20 repetitions of lifting 80% of their 1 RM by using a dumbbell. Pressure pain threshold and tolerance tests were repeated 10, 20 and 30 minutes, and 24 and 48 hours following exercise. One week after eccentric exercise, sport massage protocol for 10 minutes was manually administered to the dominant arm immediately after exercise, and all measurements were repeated at the same timeline as eccentric exercise. Results are presented as mean + standart deviation. Data of the same timeline were analyzed by using t test. A level of p<0.05 was accepted statistical significant. Eccentric exercise resulted to increase the pain tolerance from muscle and myofascia regions of m. biceps and triceps br achii, and sport massage was found to decrease the pain tolerance at 10 minutes from muscle regions of m. biceps and triceps brachii, 10, 20 and 30 minutes from myofascial region of biceps brachii, and 20 minutes, 24 and 48 hours from myofascial region of m. triceps brachii following acute bout of eccentric exercise in athletes. We concluded that sport massage reduces the hypoalgesic response during acute and delayed period of recovery after eccentric exercise.

  14. Endogenous pain modulation in response to exercise in patients with rheumatoid arthritis, patients with chronic fatigue syndrome and comorbid fibromyalgia, and healthy controls: a double-blind randomized controlled trial.

    Science.gov (United States)

    Meeus, Mira; Hermans, Linda; Ickmans, Kelly; Struyf, Filip; Van Cauwenbergh, Deborah; Bronckaerts, Laura; De Clerck, Luc S; Moorken, Greta; Hans, Guy; Grosemans, Sofie; Nijs, Jo

    2015-02-01

    Temporal summation (TS) of pain, conditioned pain modulation (CPM), and exercise-induced analgesia (EIA) are often investigated in chronic pain populations as an indicator for enhanced pain facilitation and impaired endogenous pain inhibition, respectively, but interactions are not yet clear both in healthy controls and in chronic pain patients. Therefore, the present double-blind randomized placebo-controlled study evaluates pains cores, TS, and CPM in response to exercise in healthy controls, patients with chronic fatigue syndrome and comorbid fibromyalgia (CFS/FM), and patients with rheumatoid arthritis (RA), both under placebo and paracetamol condition. Fifty-three female volunteers - of which 19 patients with CFS/FM, 16 patients with RA, and 18 healthy controls - underwent a submaximal exercise test on a bicycle ergometer on 2 different occasions (paracetamol vs. placebo), with an interval of 7 days. Before and after exercise, participants rated pain intensity during TS and CPM. Patients with rheumatoid arthritis showed decreased TS after exercise, both after paracetamol and placebo (P < 0.05). In patients with CFS/FM, results were less univocal. A nonsignificant decrease in TS was only observed after taking paracetamol. CPM responses to exercise are inconclusive, but seem to worsen after exercise. No adverse effects were seen. This study evaluates pain scores, TS, and CPM in response to submaximal exercise in 2 different chronic pain populations and healthy controls. In patients with RA, exercise had positive effects on TS, suggesting normal EIA. In patients with CFS/FM, these positive effects were only observed after paracetamol and results were inconsistent. © 2014 World Institute of Pain.

  15. Sensitivity to Pain Traumatization: A Higher-Order Factor Underlying Pain-Related Anxiety, Pain Catastrophizing and Anxiety Sensitivity among Patients Scheduled for Major Surgery

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    Valery Kleiman

    2011-01-01

    Full Text Available BACKGROUND: The present article addresses two related developments in the psychology of pain, and integrates them into a coherent framework to better understand the relationship between pain and trauma. The first is an emerging conceptualization regarding the nature of the hierarchical organization of major pain-related anxiety constructs. The second is the theoretical rationale and empirical evidence linking pain and symptoms of post-traumatic stress disorder.

  16. Safety Analysis of Solar Module under Partial Shading

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    Wei He

    2015-01-01

    Full Text Available Hot spot often occurs in a module when the qualities of solar cells mismatch and bypass diodes are proved to be an efficient alternative to reduce the effect of hot spot. However, these principles choosing a diode are based on the parameters of bypass diodes and PV cells without consideration of the maximum heating power of the shaded cell, which may cause serious consequences. On this basis, this paper presents a new approach to investigate partially shaded cells in different numbers of PV cells and different shading scenarios, including inhomogeneous illumination among solar cells and incomplete shading in one cell, which innovatively combines the same cells or divides one affected cell into many small single cells and then combines the same ones, and analyzes the shaded cell. The results indicate that the maximum power dissipation of the shaded cell occurs at short-circuit conditions. With the number of solar cells increasing, the shaded cell transfers from generating power to dissipating power and there is a maximum point of power dissipation in different shading situations that may lead to severe hot spot. Adding up the heat converted from solar energy, the heating power can be higher. In this case, some improvements about bypass diodes are proposed to reduce hot spot.

  17. Cholinergic transmission underlies modulation of frustration by open field exposure.

    Science.gov (United States)

    Psyrdellis, Mariana; Pautassi, Ricardo Marcos; Mustaca, Alba; Justel, Nadia

    2016-01-01

    Frustration can be defined as an emotional state generated by the omission or devaluation in the quantity or quality of an expected appetitive reward. Thus, reactivity to a reward is affected by prior experience with the different reinforcer values of that reward. This phenomenon is known as incentive relativity, and can be studied by different paradigms. Although methodologically simple, the exploration of a novel open field (OF) is a complex situation that involves several behavioral processes, including stress induction and novelty detection. OF exposure can enhance or block the acquisition of associative and non-associative memories. These experiments evaluated the effect of OF exploration on frustration and the role played by the cholinergic system in this phenomenon. OF exploration before first or second trial of incentive downshift modulated the expression of frustration. This effect of OF was blocked by the administration of scopolamine either before or after OF exploration. These results indicate that the cholinergic system is involved in the acquisition and consolidation of OF information.

  18. A Combined Water Extract of Frankincense and Myrrh Alleviates Neuropathic Pain in Mice via Modulation of TRPV1

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    Danyou Hu

    2017-01-01

    Full Text Available Frankincense and myrrh are widely used in clinics as a pair of herbs to obtain a synergistic effect for relieving pain. To illuminate the analgesia mechanism of frankincense and myrrh, we assessed its effect in a neuropathic pain mouse model. Transient receptor potential vanilloid 1 (TRPV1 plays a crucial role in neuropathic pain and influences the plasticity of neuronal connectivity. We hypothesized that the water extraction of frankincense and myrrh (WFM exerted its analgesia effect by modulating the neuronal function of TRPV1. In our study, WFM was verified by UHPLC-TQ/MS assay. In vivo study showed that nociceptive response in mouse by heat and capsaicin induced were relieved by WFM treatment. Furthermore, thermal hypersensitivity and mechanical allodynia were also alleviated by WFM treatment in a chronic constriction injury (CCI mouse model. CCI resulted in increased TRPV1 expression at both the mRNA and protein levels in predominantly small-to-medium neurons. However, after WFM treatment, TRPV1 expression was reverted in real-time PCR, Western blot, and immunofluorescence experiments. Calcium response to capsaicin was also decreased in cultured DRG neurons from CCI model mouse after WFM treatment. In conclusion, WFM alleviated CCI-induced mechanical allodynia and thermal hypersensitivity via modulating TRPV1.

  19. A + B → C reaction fronts in Hele-Shaw cells under modulated gravitational acceleration.

    Science.gov (United States)

    Eckert, Kerstin; Rongy, Laurence; De Wit, Anne

    2012-05-28

    The dynamics of A + B → C reaction fronts is studied under modulated gravitational acceleration by means of a combination of parabolic flight experiments and numerical simulations. During modulated gravity the front position undergoes periodic modulation with an accelerated front propagation under hyper-gravity together with a slowing down under low gravity. The underlying reason for this is an amplification and a decay, respectively, of the buoyancy-driven double vortex associated with the front propagation under standard gravitational acceleration, as explained by reaction-diffusion-convection simulations of convection around an A + B → C front. Deeper insights into the correlation between grey-value changes in the experimental shadowgraph images and characteristic changes in the concentration profiles are obtained by a numerical simulation of the imaging process.

  20. Effect of transcutaneous electromyostimulation on pressure pain threshold and tolerance in athletes under eccentric exercise

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    Selman Burak UĞURLU

    2014-08-01

    Full Text Available Exercise - induced hypoalgesia typically reported during and / or follow ing exercise. In this study, we investigated the role of transcutaneous electromyostimulation (EMS on pressure pain threshold and tolerance in athletes under eccentric exercise. Eleven male athletes aged 23,125 ± 0,99 years with 10,25 ± 2,66 years of athl etic training were recruited for this study . Following baseline measurements of pressure pain threshold and tolerance from m. biceps brachii and m. triceps brachii muscle and myofascial regions of the dominant upper extremity by using a digital algometer, subjects were underwent an acute bout of eccentric exercise. Participants were completed 4 sets of eccentric exercise each comprising 20 repetitions of lifting 80% of their 1 RM by using a dumbbell. Pressure pain threshold and tolerance tests were repeated 10, 20 and 30 minutes, and 24 and 48 hours following exercise. One week after acute exercise protocol, EMS protocol was applied to the participants immediately following eccentric exercise, and all measurements were repeated at the same timeline as eccent ric exercise. Standard EMS protocol at active recovery mode for 10 minutes was applied to the m. biceps brachii muscle by using surface electrodes. Results are presented as mean + standarts deviation. Data of the same timeline were analyzed by using repeat ed measures of ANOVA followed by Tukey’s post hoc test . A level of p<0.05 was accepted statistical significant. Eccentric exercise resulted to increase the pain tolerence in athletes, and EMS was found to decrease the pain tolerence 10 and 20 minutes at th e muscle region, and 10 and 30 minutes, and 24 hours at the myofascial region of m. biceps brachii, 10 min and 24 hr from muscle region, 10 and 30 min and 24 hr from myofascial region of M. triceps brachii following acute bout of eccentric exercise. We con cluded that EMS at active recovery phase mitigates the the hypoalgesic response following single bout of

  1. Optogenetic dissection reveals multiple rhythmogenic modules underlying locomotion

    DEFF Research Database (Denmark)

    Hägglund, Martin; Dougherty, Kimberly J.; Borgius, Lotta

    2013-01-01

    optogenetics to dissect the excitatory and inhibitory neuronal populations and probe the organization of the mammalian central pattern generator. We find that locomotor-like rhythmic bursting can be induced unilaterally or independently in flexor or extensor networks. Furthermore, we show that individual...... flexor motor neuron pools can be recruited into bursting without any activity in other nearby flexor motor neuron pools. Our experiments differentiate among several proposed models for rhythm generation in the vertebrates and show that the basic structure underlying the locomotor network has...

  2. Social cues modulate the representations underlying cross-situational learning.

    Science.gov (United States)

    MacDonald, Kyle; Yurovsky, Daniel; Frank, Michael C

    2017-05-01

    Because children hear language in environments that contain many things to talk about, learning the meaning of even the simplest word requires making inferences under uncertainty. A cross-situational statistical learner can aggregate across naming events to form stable word-referent mappings, but this approach neglects an important source of information that can reduce referential uncertainty: social cues from speakers (e.g., eye gaze). In four large-scale experiments with adults, we tested the effects of varying referential uncertainty in cross-situational word learning using social cues. Social cues shifted learners away from tracking multiple hypotheses and towards storing only a single hypothesis (Experiments 1 and 2). In addition, learners were sensitive to graded changes in the strength of a social cue, and when it became less reliable, they were more likely to store multiple hypotheses (Experiment 3). Finally, learners stored fewer word-referent mappings in the presence of a social cue even when given the opportunity to visually inspect the objects for the same amount of time (Experiment 4). Taken together, our data suggest that the representations underlying cross-situational word learning of concrete object labels are quite flexible: In conditions of greater uncertainty, learners store a broader range of information. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Plasticity-Related PKMζ Signaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury

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    Jeongsoo Han

    2015-01-01

    Full Text Available The insular cortex (IC is associated with important functions linked with pain and emotions. According to recent reports, neural plasticity in the brain including the IC can be induced by nerve injury and may contribute to chronic pain. Continuous active kinase, protein kinase Mζ (PKMζ, has been known to maintain the long-term potentiation. This study was conducted to determine the role of PKMζ in the IC, which may be involved in the modulation of neuropathic pain. Mechanical allodynia test and immunohistochemistry (IHC of zif268, an activity-dependent transcription factor required for neuronal plasticity, were performed after nerve injury. After ζ-pseudosubstrate inhibitory peptide (ZIP, a selective inhibitor of PKMζ injection, mechanical allodynia test and immunoblotting of PKMζ, phospho-PKMζ (p-PKMζ, and GluR1 and GluR2 were observed. IHC demonstrated that zif268 expression significantly increased in the IC after nerve injury. Mechanical allodynia was significantly decreased by ZIP microinjection into the IC. The analgesic effect lasted for 12 hours. Moreover, the levels of GluR1, GluR2, and p-PKMζ were decreased after ZIP microinjection. These results suggest that peripheral nerve injury induces neural plasticity related to PKMζ and that ZIP has potential applications for relieving chronic pain.

  4. δ-opioid receptor and somatostatin receptor-4 heterodimerization: possible implications in modulation of pain associated signaling.

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    Rishi K Somvanshi

    Full Text Available Pain relief is the principal action of opioids. Somatostatin (SST, a growth hormone inhibitory peptide is also known to alleviate pain even in cases when opioids fail. Recent studies have shown that mice are prone to sustained pain and devoid of analgesic effect in the absence of somatostatin receptor 4 (SSTR4. In the present study, using brain slices, cultured neurons and HEK-293 cells, we showed that SSTR4 and δ-Opioid receptor (δOR exist in a heteromeric complex and function in synergistic manner. SSTR4 and δOR co-expressed in cortical/striatal brain regions and spinal cord. Using cultured neuronal cells, we describe the heterogeneous complex formation of SSTR4 and δOR at neuronal cell body and processes. Cotransfected cells display inhibition of cAMP/PKA and co-activation of SSTR4 and δOR oppose receptor trafficking induced by individual receptor activation. Furthermore, downstream signaling pathways either associated with withdrawal or pain relief are modulated synergistically with a predominant role of SSTR4. Inhibition of cAMP/PKA and activation of ERK1/2 are the possible cellular adaptations to prevent withdrawal induced by chronic morphine use. Our results reveal direct intra-membrane interaction between SSTR4 and δOR and provide insights for the molecular mechanism for the anti-nociceptive property of SST in combination with opioids as a potential therapeutic approach to avoid undesirable withdrawal symptoms.

  5. Neural mechanism underlying autobiographical memory modulated by remoteness and emotion

    Science.gov (United States)

    Ge, Ruiyang; Fu, Yan; Wang, DaHua; Yao, Li; Long, Zhiying

    2012-03-01

    Autobiographical memory is the ability to recollect past events from one's own life. Both emotional tone and memory remoteness can influence autobiographical memory retrieval along the time axis of one's life. Although numerous studies have been performed to investigate brain regions involved in retrieving processes of autobiographical memory, the effect of emotional tone and memory age on autobiographical memory retrieval remains to be clarified. Moreover, whether the involvement of hippocampus in consolidation of autobiographical events is time dependent or independent has been controversial. In this study, we investigated the effect of memory remoteness (factor1: recent and remote) and emotional valence (factor2: positive and negative) on neural correlates underlying autobiographical memory by using functional magnetic resonance imaging (fMRI) technique. Although all four conditions activated some common regions known as "core" regions in autobiographical memory retrieval, there are some other regions showing significantly different activation for recent versus remote and positive versus negative memories. In particular, we found that bilateral hippocampal regions were activated in the four conditions regardless of memory remoteness and emotional valence. Thus, our study confirmed some findings of previous studies and provided further evidence to support the multi-trace theory which believes that the role of hippocampus involved in autobiographical memory retrieval is time-independent and permanent in memory consolidation.

  6. Negative Affectivity, Depression, and Resting Heart Rate Variability (HRV as Possible Moderators of Endogenous Pain Modulation in Functional Somatic Syndromes

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    Maaike Van Den Houte

    2018-03-01

    Full Text Available Background: Several studies have shown that patients with functional somatic syndromes (FSS have, on average, deficient endogenous pain modulation (EPM, as well as elevated levels of negative affectivity (NA and high comorbidity with depression and reduced resting heart rate variability (HRV compared to healthy controls (HC. The goals of this study were (1 to replicate these findings and (2 to investigate the moderating role of NA, depression, and resting HRV in EPM efficiency within a patient group with fibromyalgia and/or chronic fatigue syndrome (CFS. Resting HRV was quantified as the root mean square of successive differences between inter-beat intervals (RMSSD in rest, a vagally mediated time domain measure of HRV.Methods: Seventy-eight patients with fibromyalgia and/or CFS and 33 HC completed a counter-irritation paradigm as a measure of EPM efficiency. Participants rated the painfulness of electrocutaneous stimuli (of individually calibrated intensity on the ankle before (baseline phase, during (counter-irritation phase and after (recovery phase the application of a cold pain stimulus on the forearm. A larger reduction in pain in the counter-irritation phase compared to the baseline phase reflects a more efficient EPM.Results: In contrast to our expectations, there was no difference between pain ratings in the baseline compared to counter-irritation phase for both patients and HC. Therefore, reliable conclusions on the moderating effect of NA, depression, and RMSSD could not be made. Surprisingly, patients reported more pain in the recovery compared to the counter-irritation and baseline phase, while HC did not. This latter effect was more pronounced in patients with comorbid depression, patients who rated the painfulness of the counter-irritation stimulus as high and patients who rated the painfulness of the electrocutaneous stimuli as low. We did not manage to successfully replicate the counter-irritation effect in HC or FSS patients

  7. Cultural modulation of the neural correlates of emotional pain perception: the role of other-focusedness.

    Science.gov (United States)

    Cheon, Bobby K; Im, Dong-Mi; Harada, Tokiko; Kim, Ji-Sook; Mathur, Vani A; Scimeca, Jason M; Parrish, Todd B; Park, Hyunwook; Chiao, Joan Y

    2013-06-01

    Cultures vary in the extent to which they emphasize group members to habitually attend to the needs, perspectives, and internal experiences of others compared to the self. Here we examined the influence that collectivistic and individualistic cultural environments may play on the engagement of the neurobiological processes that underlie the perception and processing of emotional pain. Using cross-cultural fMRI, Korean and Caucasian-American participants passively viewed scenes of others in situations of emotional pain and distress. Regression analyses revealed that the value of other-focusedness was associated with heightened neural response within the affective pain matrix (i.e. anterior cingulate cortex and insula) to a greater extent for Korean relative to Caucasian-American participants. These findings suggest that mindsets promoting attunement to the subjective experience of others may be especially critical for pain-related and potentially empathic processing within collectivistic relative to individualistic cultural environments. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. 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.

  9. Device Loading and Efficiency of Modular Multilevel Converter under Various Modulation Strategies

    DEFF Research Database (Denmark)

    Liu, Hui; Ma, Ke; Blaabjerg, Frede

    2016-01-01

    ), Phase Disposition PWM (PDPWM) and Nearest Level Modulation (NLM), are comprehensively investigated to uncover the desired solution for high transmission efficiency and system reliability. An important part of this paper is also devoted to reveal the impact of modulation schemes on the loading stress...... of the power devices in terms of power loss and thermal profiles, which are critical issues in terms of efficiency and reliability of the MMC. Special attention is given to the performance comparison of MMC under various modulation indexes as well as different switching frequencies when applying those...

  10. Beam steering of the acoustic metasurface under a subwavelength periodic modulation

    Science.gov (United States)

    Cai, Li; Wen, Jihong; Yu, Dianlong; Lu, Zhimiao; Chen, Xing; Zhao, Xiang

    2017-11-01

    In this study, we introduce a subwavelength periodic thin plate array into an acoustic metasurface and investigate the modulation effect on acoustic surface waves. Both anomalous sound refraction and reflection are observed in the metasurface, and an analytic expression is derived to clarify the underlying mechanism. We theoretically prove that flexible beam steering can be realized by phase gradient acoustic metasurfaces with deep subwavelength periodic modulation. This study potentially adds another degree of freedom to controlling sound transmission by using an acoustic metasurface.

  11. Arginine vasopressin induces periaqueductal gray release of enkephalin and endorphin relating to pain modulation in the rat.

    Science.gov (United States)

    Yang, Jun; Yang, Yu; Xu, Hong-Tao; Chen, Jian-Min; Liu, Wen-Yan; Lin, Bao-Cheng

    2007-07-05

    Previous study has proven that microinjection of arginine vasopressin (AVP) into periaqueductal gray (PAG) raises the pain threshold, in which the antinociceptive effect of AVP can be reversed by PAG pretreatment with V2 rather than V1 or opiate receptor antagonist. The present work investigated the AVP effect on endogenous opiate peptides, oxytocin (OXT) and classical neurotransmitters in the rat PAG. The results showed that AVP elevated the concentrations of leucine-enkephalin (L-Ek), methionine-enkephalin (M-Ek) and beta-endorphin (beta-Ep), but did not change the concentrations of dynorphinA(1-13) (DynA(1-13)), OXT, classical neurotransmitters including achetylcholine (Ach), choline (Ch), serotonin (5-HT), gamma-aminobutyric acid (GABA), glutamate (Glu), dopamine (DA), norepinephrine (NE) and epinephrine (E), and their metabolic products in PAG perfusion liquid. Pain stimulation increased the concentrations of AVP, L-EK, M-Ek, beta-Ep, 5-HT and 5-HIAA (5-HT metabolic product), but did not influence the concentrations of DynA(1-13), OXT, the other classical neurotransmitters and their metabolic products. PAG pretreatment with naloxone - an opiate receptor antagonist completely attenuated the pain threshold increase induced by PAG administration of AVP, but local pretreatment of OXT or classical neurotransmitter receptor antagonist did not influence the pain threshold increase induced by PAG administration of AVP. The data suggested that AVP in PAG could induce the local release of enkephalin and endorphin rather than dynophin, OXT and classical neurotransmitters to participate in pain modulation.

  12. Tempol modulates changes in xenobiotic permeability and occludin oligomeric assemblies at the blood-brain barrier during inflammatory pain

    Science.gov (United States)

    Lochhead, Jeffrey J.; McCaffrey, Gwen; Sanchez-Covarrubias, Lucy; Finch, Jessica D.; DeMarco, Kristin M.; Quigley, Colleen E.; Davis, Thomas P.

    2012-01-01

    Our laboratory has shown that λ-carrageenan-induced peripheral inflammatory pain (CIP) can alter tight junction (TJ) protein expression and/or assembly leading to changes in blood-brain barrier xenobiotic permeability. However, the role of reactive oxygen species (ROS) and subsequent oxidative stress during CIP is unknown. ROS (i.e., superoxide) are known to cause cellular damage in response to pain/inflammation. Therefore, we examined oxidative stress-associated effects at the blood-brain barrier (BBB) in CIP rats. During CIP, increased staining of nitrosylated proteins was detected in hind paw tissue and enhanced presence of protein adducts containing 3-nitrotyrosine occurred at two molecular weights (i.e., 85 and 44 kDa) in brain microvessels. Tempol, a pharmacological ROS scavenger, attenuated formation of 3-nitrotyrosine-containing proteins in both the hind paw and in brain microvessels when administered 10 min before footpad injection of λ-carrageenan. Similarly, CIP increased 4-hydroxynoneal staining in brain microvessels and this effect was reduced by tempol. Brain permeability to [14C]sucrose and [3H]codeine was increased, and oligomeric assemblies of occludin, a critical TJ protein, were altered after 3 h CIP. Tempol attenuated both [14C]sucrose and [3H]codeine brain uptake as well as protected occludin oligomers from disruption in CIP animals, suggesting that ROS production/oxidative stress is involved in modulating BBB functional integrity during pain/inflammation. Interestingly, tempol administration reduced codeine analgesia in CIP animals, indicating that oxidative stress during pain/inflammation may affect opioid delivery to the brain and subsequent efficacy. Taken together, our data show for the first time that ROS pharmacological scavenging is a viable approach for maintaining BBB integrity and controlling central nervous system drug delivery during acute inflammatory pain. PMID:22081706

  13. Pain perception and hypnosis: findings from recent functional neuroimaging studies.

    Science.gov (United States)

    Del Casale, Antonio; Ferracuti, Stefano; Rapinesi, Chiara; Serata, Daniele; Caltagirone, Saverio Simone; Savoja, Valeria; Piacentino, Daria; Callovini, Gemma; Manfredi, Giovanni; Sani, Gabriele; Kotzalidis, Georgios D; Girardi, Paolo

    2015-01-01

    Hypnosis modulates pain perception and tolerance by affecting cortical and subcortical activity in brain regions involved in these processes. By reviewing functional neuroimaging studies focusing on pain perception under hypnosis, the authors aimed to identify brain activation-deactivation patterns occurring in hypnosis-modulated pain conditions. Different changes in brain functionality occurred throughout all components of the pain network and other brain areas. The anterior cingulate cortex appears to be central in modulating pain circuitry activity under hypnosis. Most studies also showed that the neural functions of the prefrontal, insular, and somatosensory cortices are consistently modified during hypnosis-modulated pain conditions. Functional neuroimaging studies support the clinical use of hypnosis in the management of pain conditions.

  14. Pain Modulation in Waking and Hypnosis in Women: Event-Related Potentials and Sources of Cortical Activity

    Science.gov (United States)

    De Pascalis, Vilfredo; Varriale, Vincenzo; Cacace, Immacolata

    2015-01-01

    Using a strict subject selection procedure, we tested in High and Low Hypnotizable subjects (HHs and LHs) whether treatments of hypoalgesia and hyperalgesia, as compared to a relaxation-control, differentially affected subjective pain ratings and somatosensory event-related potentials (SERPs) during painful electric stimulation. Treatments were administered in waking and hypnosis conditions. LHs showed little differentiation in pain and distress ratings between hypoalgesia and hyperalgesia treatments, whereas HHs showed a greater spread in the instructed direction. HHs had larger prefrontal N140 and P200 waves of the SERPs during hypnotic hyperalgesia as compared to relaxation-control treatment. Importantly, HHs showed significant smaller frontocentral N140 and frontotemporal P200 waves during hypnotic hypoalgesia. LHs did not show significant differences for these SERP waves among treatments in both waking and hypnosis conditions. Source localization (sLORETA) method revealed significant activations of the bilateral primary somatosensory (BA3), middle frontal gyrus (BA6) and anterior cingulate cortices (BA24). Activity of these contralateral regions significantly correlated with subjective numerical pain scores for control treatment in waking condition. Moreover, multivariate regression analyses distinguished the contralateral BA3 as the only region reflecting a stable pattern of pain coding changes across all treatments in waking and hypnosis conditions. More direct testing showed that hypnosis reduced the strength of the association of pain modulation and brain activity changes at BA3. sLORETA in HHs revealed, for the N140 wave, that during hypnotic hyperalgesia, there was an increased activity within medial, supramarginal and superior frontal gyri, and cingulated gyrus (BA32), while for the P200 wave, activity was increased in the superior (BA22), middle (BA37), inferior temporal (BA19) gyri and superior parietal lobule (BA7). Hypnotic hypoalgesia in HHs, for N

  15. Pain modulation in waking and hypnosis in women: event-related potentials and sources of cortical activity.

    Directory of Open Access Journals (Sweden)

    Vilfredo De Pascalis

    Full Text Available Using a strict subject selection procedure, we tested in High and Low Hypnotizable subjects (HHs and LHs whether treatments of hypoalgesia and hyperalgesia, as compared to a relaxation-control, differentially affected subjective pain ratings and somatosensory event-related potentials (SERPs during painful electric stimulation. Treatments were administered in waking and hypnosis conditions. LHs showed little differentiation in pain and distress ratings between hypoalgesia and hyperalgesia treatments, whereas HHs showed a greater spread in the instructed direction. HHs had larger prefrontal N140 and P200 waves of the SERPs during hypnotic hyperalgesia as compared to relaxation-control treatment. Importantly, HHs showed significant smaller frontocentral N140 and frontotemporal P200 waves during hypnotic hypoalgesia. LHs did not show significant differences for these SERP waves among treatments in both waking and hypnosis conditions. Source localization (sLORETA method revealed significant activations of the bilateral primary somatosensory (BA3, middle frontal gyrus (BA6 and anterior cingulate cortices (BA24. Activity of these contralateral regions significantly correlated with subjective numerical pain scores for control treatment in waking condition. Moreover, multivariate regression analyses distinguished the contralateral BA3 as the only region reflecting a stable pattern of pain coding changes across all treatments in waking and hypnosis conditions. More direct testing showed that hypnosis reduced the strength of the association of pain modulation and brain activity changes at BA3. sLORETA in HHs revealed, for the N140 wave, that during hypnotic hyperalgesia, there was an increased activity within medial, supramarginal and superior frontal gyri, and cingulated gyrus (BA32, while for the P200 wave, activity was increased in the superior (BA22, middle (BA37, inferior temporal (BA19 gyri and superior parietal lobule (BA7. Hypnotic hypoalgesia in

  16. Pain modulation in waking and hypnosis in women: event-related potentials and sources of cortical activity.

    Science.gov (United States)

    De Pascalis, Vilfredo; Varriale, Vincenzo; Cacace, Immacolata

    2015-01-01

    Using a strict subject selection procedure, we tested in High and Low Hypnotizable subjects (HHs and LHs) whether treatments of hypoalgesia and hyperalgesia, as compared to a relaxation-control, differentially affected subjective pain ratings and somatosensory event-related potentials (SERPs) during painful electric stimulation. Treatments were administered in waking and hypnosis conditions. LHs showed little differentiation in pain and distress ratings between hypoalgesia and hyperalgesia treatments, whereas HHs showed a greater spread in the instructed direction. HHs had larger prefrontal N140 and P200 waves of the SERPs during hypnotic hyperalgesia as compared to relaxation-control treatment. Importantly, HHs showed significant smaller frontocentral N140 and frontotemporal P200 waves during hypnotic hypoalgesia. LHs did not show significant differences for these SERP waves among treatments in both waking and hypnosis conditions. Source localization (sLORETA) method revealed significant activations of the bilateral primary somatosensory (BA3), middle frontal gyrus (BA6) and anterior cingulate cortices (BA24). Activity of these contralateral regions significantly correlated with subjective numerical pain scores for control treatment in waking condition. Moreover, multivariate regression analyses distinguished the contralateral BA3 as the only region reflecting a stable pattern of pain coding changes across all treatments in waking and hypnosis conditions. More direct testing showed that hypnosis reduced the strength of the association of pain modulation and brain activity changes at BA3. sLORETA in HHs revealed, for the N140 wave, that during hypnotic hyperalgesia, there was an increased activity within medial, supramarginal and superior frontal gyri, and cingulated gyrus (BA32), while for the P200 wave, activity was increased in the superior (BA22), middle (BA37), inferior temporal (BA19) gyri and superior parietal lobule (BA7). Hypnotic hypoalgesia in HHs, for N

  17. Pain hypersensitivity mechanisms at a glance.

    Science.gov (United States)

    Gangadharan, Vijayan; Kuner, Rohini

    2013-07-01

    There are two basic categories of pain: physiological pain, which serves an important protective function, and pathological pain, which can have a major negative impact on quality of life in the context of human disease. Major progress has been made in understanding the molecular mechanisms that drive sensory transduction, amplification and conduction in peripheral pain-sensing neurons, communication of sensory inputs to spinal second-order neurons, and the eventual modulation of sensory signals by spinal and descending circuits. This poster article endeavors to provide an overview of how molecular and cellular mechanisms underlying nociception in a physiological context undergo plasticity in pathophysiological states, leading to pain hypersensitivity and chronic pain.

  18. Empathy for pain-related dorsolateral prefrontal activity is modulated by angry face perception.

    Science.gov (United States)

    Enzi, Björn; Amirie, Scharbanu; Brüne, Martin

    2016-11-01

    Empathy, i.e., the ability to perceive and share another person's affective state, is associated with activity in a complex neural network, including the anterior insula, the anterior and mid-cingulate cortex, and the lateral prefrontal cortex. Here, we were interested in the question how facial emotions influence the activation of the 'pain network'. In the present study, we used functional magnetic resonance imaging to investigate the neuronal correlates of empathy for pain and its interaction with emotional face recognition in 20 healthy subjects. We identified various brain regions commonly associated with empathy for pain, including the right mid-cingulate cortex, the left anterior insula (AI), and the left dorsolateral prefrontal cortex (dlPFC), with an increased neuronal response in the left dlPFC after the presentation of angry faces. Furthermore, a negative correlation between psychological measures of alexithymia and empathy for pain-related brain activity was observed in the left AI. The dlPFC is an important brain region involved in cognitive reappraisal or in 'top-down' control of the limbic system. Our findings could therefore reflect a regulatory response associated with distancing from negatively valenced stimuli. Moreover, our results underline the involvement of the AI in empathy for pain responses and their relationship to alexithymia.

  19. RESULTS OF DIAGNOSTICAL BLOCK OF LONG DORSAL SACROILIAC LIGAMENT UNDER SONOGRAPHIC CONTROL IN PATIENTS WITH LOW BACK PAIN

    Directory of Open Access Journals (Sweden)

    Yurkovskiy A. M.

    2018-02-01

    Full Text Available Purpose: to improve effectiveness of diagnostic block of long dorsal sacroiliac ligament performed under sonographic control in patients with low back pain caused by pathology of this ligament. Material and methods: the research included 35 patients (average age 46,2±12,5 years with symptoms of low back pain caused by pathology of long dorsal sacroiliac ligament. Diagnostical block of the given ligament was made under ultrasound control. Results: significant pain syndrome reduction was observed in all patients with ligamentopathy of long dorsal sacroiliac ligament. Conclusion: compared to "blind" technique, long dorsal sacroiliac ligament block performed under sonographic control is a more efficient method of verification and treatment for low back pain syndrome in case of long dorsal sacroiliac ligament injury.

  20. The Endocannabinoid System as a Potential Therapeutic Target for Pain Modulation

    Directory of Open Access Journals (Sweden)

    Ahmet Ulugöl

    2014-06-01

    Full Text Available Although cannabis has been used for pain management for millennia, very few approved cannabinoids are indicated for the treatment of pain and other medical symptoms. Cannabinoid therapy re-gained attention only after the discovery of endocannabinoids and fatty acid amide hydrolase (FAAH and monoacylglycerol lipase (MAGL, the enzymes playing a role in endocannabinoid metabolism. Nowadays, research has focused on the inhibition of these degradative enzymes and the elevation of endocannabinoid tonus locally; special emphasis is given on multi-target analgesia compounds, where one of the targets is the endocannabinoid degrading enzyme. In this review, I provide an overview of the current understanding about the processes accounting for the biosynthesis, transport and metabolism of endocannabinoids, and pharmacological approaches and potential therapeutic applications in this area, regarding the use of drugs elevating endocannabinoid levels in pain conditions.

  1. Dry Needling at Myofascial Trigger Spots of Rabbit Skeletal Muscles Modulates the Biochemicals Associated with Pain, Inflammation, and Hypoxia

    Science.gov (United States)

    Hsieh, Yueh-Ling; Yang, Shun-An; Yang, Chen-Chia; Chou, Li-Wei

    2012-01-01

    Background and Purpose. Dry needling is an effective therapy for the treatment of pain associated with myofascial trigger point (MTrP). However, the biochemical effects of dry needling that are associated with pain, inflammation, and hypoxia are unclear. This study investigated the activities of β-endorphin, substance P, TNF-α, COX-2, HIF-1α, iNOS, and VEGF after different dosages of dry needling at the myofascial trigger spots (MTrSs) of a skeletal muscle in rabbit. Materials and Methods. Dry needling was performed either with one dosage (1D) or five dosages (5D) into the biceps femoris with MTrSs in New Zealand rabbits. Biceps femoris, serum, and dorsal root ganglion (DRG) were sampled immediately and 5 d after dry needling for β-endorphin, substance P, TNF-α, COX-2, HIF-1α, iNOS, and VEGF immunoassays. Results. The 1D treatment enhanced the β-endorphin levels in the biceps femoris and serum and reduced substance P in the biceps femoris and DRG. The 5D treatment reversed these effects and was accompanied by increase of TNF-α, COX-2, HIF-1α, iNOS, and VEGF production in the biceps femoris. Moreover, the higher levels of these biochemicals were still maintained 5 d after treatment. Conclusion. Dry needling at the MTrSs modulates various biochemicals associated with pain, inflammation, and hypoxia in a dose-dependent manner. PMID:23346198

  2. Dry Needling at Myofascial Trigger Spots of Rabbit Skeletal Muscles Modulates the Biochemicals Associated with Pain, Inflammation, and Hypoxia

    Directory of Open Access Journals (Sweden)

    Yueh-Ling Hsieh

    2012-01-01

    Full Text Available Background and Purpose. Dry needling is an effective therapy for the treatment of pain associated with myofascial trigger point (MTrP. However, the biochemical effects of dry needling that are associated with pain, inflammation, and hypoxia are unclear. This study investigated the activities of β-endorphin, substance P, TNF-α, COX-2, HIF-1α, iNOS, and VEGF after different dosages of dry needling at the myofascial trigger spots (MTrSs of a skeletal muscle in rabbit. Materials and Methods. Dry needling was performed either with one dosage (1D or five dosages (5D into the biceps femoris with MTrSs in New Zealand rabbits. Biceps femoris, serum, and dorsal root ganglion (DRG were sampled immediately and 5 d after dry needling for β-endorphin, substance P, TNF-α, COX-2, HIF-1α, iNOS, and VEGF immunoassays. Results. The 1D treatment enhanced the β-endorphin levels in the biceps femoris and serum and reduced substance P in the biceps femoris and DRG. The 5D treatment reversed these effects and was accompanied by increase of TNF-α, COX-2, HIF-1α, iNOS, and VEGF production in the biceps femoris. Moreover, the higher levels of these biochemicals were still maintained 5 d after treatment. Conclusion. Dry needling at the MTrSs modulates various biochemicals associated with pain, inflammation, and hypoxia in a dose-dependent manner.

  3. Virtual Visual Effect of Hospital Waiting Room on Pain Modulation in Healthy Subjects and Patients with Chronic Migraine

    Directory of Open Access Journals (Sweden)

    Marina de Tommaso

    2013-01-01

    Full Text Available Environmental context has an important impact on health and well being. We aimed to test the effects of a visual distraction induced by classical hospital waiting room (RH versus an ideal room with a sea view (IH, both represented in virtual reality (VR, on subjective sensation and cortical responses induced by painful laser stimuli (LEPs in healthy volunteers and patients with chronic migraine (CM. Sixteen CM and 16 controls underwent 62 channels LEPs from the right hand, during a fully immersive VR experience, where two types of waiting rooms were simulated. The RH simulated a classical hospital waiting room while the IH represented a room with sea viewing. CM patients showed a reduction of laser pain rating and vertex LEPs during the IH vision. The sLORETA analysis confirmed that in CM patients the two VR simulations induced a different modulation of bilateral parietal cortical areas (precuneus and superior parietal lobe, and superior frontal and cingulate girus, in respect to controls. The architectural context may interfere with pain perception, depending upon the status of subject. Many variables may change patients’ outcome and support the use of VR technology to test the best conditions for their management.

  4. Physical Activity May Be Associated with Conditioned Pain Modulation in Women but Not Men among Healthy Individuals

    Directory of Open Access Journals (Sweden)

    Yukiko Shiro

    2017-01-01

    Full Text Available Background. Conditioned pain modulation (CPM, a phenomenon also known as diffuse noxious inhibitory control, is thought to be affected by various factors, including sex and level of physical activity. However, the involvement of these factors in CPM remains unclear. Methods. Eighty-six healthy young subjects (M/F, 43/43 participated in this study. Participants were assessed on the basis of their mechanical pressure pain threshold (PPT, CPM response, body mass index (BMI, basal metabolic rate (BMR, and duration of moderate-to-vigorous physical activity (MVPA over a week, using a motion counter. Response to CPM was evaluated as PPT during painful cold stimulation relative to baseline PPT. Results. Men showed significantly higher baseline PPT than women; however, this difference was no longer significant after controlling for confounders. Stepwise multiple linear regression analyses revealed BMR to be a significant contributor towards baseline PPT in the entire study population. In contrast, although there were no significant contributors to CPM response among men and in the overall study group, MVPA was positively associated with CPM response among women (β = 0.397. Conclusions. These results suggest that, among healthy young individuals, CPM response may be associated with moderate-to-vigorous physical activity in women but not in men.

  5. Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis

    Directory of Open Access Journals (Sweden)

    Izumi Masashi

    2012-08-01

    Full Text Available Abstract Background Recent data have suggested a relationship between acute arthritic pain and acid sensing ion channel 3 (ASIC3 on primary afferent fibers innervating joints. The purpose of this study was to clarify the role of ASIC3 in a rat model of osteoarthritis (OA which is considered a degenerative rather than an inflammatory disease. Methods We induced OA via intra-articular mono-iodoacetate (MIA injection, and evaluated pain-related behaviors including weight bearing measured with an incapacitance tester and paw withdrawal threshold in a von Frey hair test, histology of affected knee joint, and immunohistochemistry of knee joint afferents. We also assessed the effect of ASIC3 selective peptide blocker (APETx2 on pain behavior, disease progression, and ASIC3 expression in knee joint afferents. Results OA rats showed not only weight-bearing pain but also mechanical hyperalgesia outside the knee joint (secondary hyperalgesia. ASIC3 expression in knee joint afferents was significantly upregulated approximately twofold at Day 14. Continuous intra-articular injections of APETx2 inhibited weight distribution asymmetry and secondary hyperalgesia by attenuating ASIC3 upregulation in knee joint afferents. Histology of ipsilateral knee joint showed APETx2 worked chondroprotectively if administered in the early, but not late phase. Conclusions Local ASIC3 immunoreactive nerve is strongly associated with weight-bearing pain and secondary hyperalgesia in MIA-induced OA model. APETx2 inhibited ASIC3 upregulation in knee joint afferents regardless of the time-point of administration. Furthermore, early administration of APETx2 prevented cartilage damage. APETx2 is a novel, promising drug for OA by relieving pain and inhibiting disease progression.

  6. Efficacy of an acquainted drug in the treatment of inflammatory low back pain: sulfasalazine under investigation

    Directory of Open Access Journals (Sweden)

    Moghimi J

    2016-09-01

    Full Text Available Jamileh Moghimi,1 Ali Asghar Rezaei,2 Raheb Ghorbani,3 Mohammad Reza Razavi,4 Daryoush Pahlevan3 1Department of Rheumatology, Clinical Research Development Unit (CRDU, 2Clinical Research Development Unit (CRDU, Kowsar Hospital, 3Social Determinants of Health Research Center, Department of Community Medicine, Faculty of Medicine; 4Nursing Care Research Center, Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran Abstract: In the current study, the overall prevalence and the main underlying etiologies of inflammatory low back pain (ILBP were determined, and the effectiveness of treatment with sulfasalazine was investigated in patients with inflammatory versus mechanical low back pain (LBP. In a prospective study conducted from July 2013 until August 2015, 1,779 consecutive patients within the age range of 18–50 years with a primary complaint of LBP referring to the rheumatology clinics were included. The patients were classified into two distinct groups: those suffering from ILBP (n=118 and those having mechanical LBP (n=1,661. Patients were followed-up for assessing the response rate to sulfasalazine with a mean follow-up time of 16 months. Results showed that among the total number of participants, 6.6% suffered from ILBP. The main underlying diagnoses of ILBP were undifferentiated spondyloarthropathy (USpA (61.0% and ankylosing spondylitis (24.6%. During the follow-up period, 3.4% of the participants had an appropriate response to only nonsteroidal anti-inflammatory drugs, 57.6% to sulfasalazine, 26.3% to addition of methotrexate to the previous regimen, and 12.7% to biological agents. Multiple logistic regression results showed that the underlying disease had a significant effect on the sulfasalazine response. The odds for response to treatment was 3.53 times higher in USpA patients compared to other patients (odds ratio =3.53, 95% confidence interval: 1.63–7.68, P=0.001. In 69.4% of the participants, the

  7. Predictability of painful stimulation modulates the somatosensory-evoked potential in the rat

    NARCIS (Netherlands)

    Schaap, M.W.H.; van Oostrom, H.; Doornenbal, A.; Baars, A.M.; Arndt, S.S.; Hellebrekers, L.J.

    2013-01-01

    Abstract Somatosensory-evoked potentials (SEPs) are used in humans and animals to increase knowledge about nociception and pain. Since the SEP in humans increases when noxious stimuli are administered unpredictably, predictability potentially influences the SEP in animals as well. To assess the

  8. Too Hard to Control: Compromised Pain Anticipation and Modulation in Mild Traumatic Brain Injury

    Science.gov (United States)

    2014-01-07

    insula activation during pain anticipation in individuals recovered from anorexia nervosa : evidence of interoceptive dysregulation. Int J Eat Disord ...criteria for current mood or anxiety disorder . We found that relative to healthy comparison subjects, after controlling for traumatic and depressive...with rehabilitative care and markedly increase treatment costs.15–18 Psychiatric conditions such as post-traumatic stress disorder (PTSD) and depression

  9. Smooth Pursuit Eye Movement Deficits in Patients With Whiplash and Neck Pain are Modulated by Target Predictability.

    Science.gov (United States)

    Janssen, Malou; Ischebeck, Britta K; de Vries, Jurryt; Kleinrensink, Gert-Jan; Frens, Maarten A; van der Geest, Jos N

    2015-10-01

    This is a cross-sectional study. The purpose of this study is to support and extend previous observations on oculomotor disturbances in patients with neck pain and whiplash-associated disorders (WADs) by systematically investigating the effect of static neck torsion on smooth pursuit in response to both predictably and unpredictably moving targets using video-oculography. Previous studies showed that in patients with neck complaints, for instance due to WAD, extreme static neck torsion deteriorates smooth pursuit eye movements in response to predictably moving targets compared with healthy controls. Eye movements in response to a smoothly moving target were recorded with video-oculography in a heterogeneous group of 55 patients with neck pain (including 11 patients with WAD) and 20 healthy controls. Smooth pursuit performance was determined while the trunk was fixed in 7 static rotations relative to the head (from 45° to the left to 45° to right), using both predictably and unpredictably moving stimuli. Patients had reduced smooth pursuit gains and smooth pursuit gain decreased due to neck torsion. Healthy controls showed higher gains for predictably moving targets compared with unpredictably moving targets, whereas patients with neck pain had similar gains in response to both types of target movements. In 11 patients with WAD, increased neck torsion decreased smooth pursuit performance, but only for predictably moving targets. Smooth pursuit of patients with neck pain is affected. The previously reported WAD-specific decline in smooth pursuit due to increased neck torsion seems to be modulated by the predictability of the movement of the target. The observed oculomotor disturbances in patients with WAD are therefore unlikely to be induced by impaired neck proprioception alone. 3.

  10. E-learning module on chronic low back pain in older adults: evidence of effect on medical student objective structured clinical examination performance.

    Science.gov (United States)

    Weiner, Debra K; Morone, Natalia E; Spallek, Heiko; Karp, Jordan F; Schneider, Michael; Washburn, Carol; Dziabiak, Michael P; Hennon, John G; Elnicki, D Michael

    2014-06-01

    The Institute of Medicine has highlighted the urgent need to close undergraduate and graduate educational gaps in treating pain. Chronic low back pain (CLBP) is one of the most common pain conditions, and older adults are particularly vulnerable to potential morbidities associated with misinformed treatment. An e-learning case-based interactive module was developed at the University of Pittsburgh Center of Excellence in Pain Education, one of 12 National Institutes of Health-designated centers, to teach students important principles for evaluating and managing CLBP in older adults. A team of six experts in education, information technology, pain management, and geriatrics developed the module. Teaching focused on common errors, interactivity, and expert modeling and feedback. The module mimicked a patient encounter using a standardized patient (the older adult with CLBP) and a pain expert (the patient provider). Twenty-eight medical students were not exposed to the module (Group 1) and 27 were exposed (Group 2). Their clinical skills in evaluating CLBP were assessed using an objective structured clinical examination (OSCE). Mean scores were 62.0 ± 8.6 for Group 1 and 79.5 ± 10.4 for Group 2 (P students (60.7%) and 26 of 27 Group 2 students (96.3%) passed. The CLBP OSCE was one of 10 OSCE stations in which students were tested at the end of a Combined Ambulatory Medicine and Pediatrics Clerkship. There were no between-group differences in performance on eight of the other nine OSCE stations. This module significantly improved medical student clinical skills in evaluating CLBP. Additional research is needed to ascertain the effect of e-learning modules on more-advanced learners and on improving the care of older adults with CLBP. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

  11. Does amplitude-modulated frequency have a role in the hypoalgesic response of interferential current on pressure pain sensitivity in healthy subjects? A randomised crossover study.

    Science.gov (United States)

    Fuentes C, Jorge; Armijo-Olivo, Susan; Magee, David J; Gross, Douglas

    2010-03-01

    To investigate the hypoalgesic effect of amplitude-modulated frequency during interferential current therapy using an experimentally induced mechanical pain model in normal subjects. This study examined pain pressure sensitivities achieved when the amplitude-modulated frequency parameter was present (100Hz) and absent (0Hz). Randomised controlled crossover trial with repeated measures. University research laboratory. Forty-six healthy volunteers (23 males, 23 females). Two interferential therapy protocols (with and without amplitude-modulated frequencies) were applied to the lumbar area on two different days. Pressure pain thresholds over the lumbar area were measured before, during and after application of the interferential therapy protocols. A three-way analysis of variance with repeated measures failed to show any statistically significant difference between the two protocols in modifying pressure pain threshold values (mean difference 0.017kg/cm(2), 95% confidence interval -0.384 to 0.350, P=0.93). Statistically significant differences were identified (Pinterferential therapy did not influence mechanical pain sensitivity in healthy subjects. Amplitude-modulated frequency is therefore unlikely to have a physiological hypoalgesic effect.

  12. Motor cortex changes after amputation are modulated by phantom limb motor control rather than pain

    DEFF Research Database (Denmark)

    Raffin, Estelle E.; Pascal, Giraux,; Karen, Reilly,

    Amputation of a limb induces reorganization within the contralateral primary motor cortex (M1-c) (1-3). In the case of hand amputation, M1-c areas evoking movements in the face and the remaining part of the upper-limb expand toward the hand area. Despite this expansion, the amputated hand still...... retains a residual M1-c activity when amputees perform phantom limb movements (4-5). Except a correlation between phantom limb pain and M1-c expansion of the face (2-3), the relationship between the ability to voluntary move the phantom hand, the level of phantom limb pain, the degree of M1-c...... reorganization and the residual M1-c activity of the amputated hand is unknown. This fMRI study aimed to determine this relationship...

  13. Biophysical parameters of erythrocyte membranes and mechanisms of interaction with non-opioid analgesics under acute pain syndrome

    Directory of Open Access Journals (Sweden)

    Yu. I. Gubskyi

    2014-06-01

    Full Text Available Methods of fluorescent probing, spectrophotometry and microcalorimetry were applied to investigate the alterations in biophysical parameters of erythrocytes membranes, and specifically microviscosity, surface charge, molecular organization of lipid bilayer and lipid-protein interactions under conditions of acute pain syndrome produced by experimental chemical lesion. The distinctive features of non-opiod analgesics interactions and binding to the erythrocytes membranes of rats subjected to acute nociceptive pain accompanied with oxidative stress development were investigated. The abilities of analgesics under research, and namely paracetamol, aspirin, phenazone, ketorolac, pyrodazole, ketoprofenum, natrium mefenaminate, indometacin, nimesulide to make up physico-chemical complexes with lipoperoxidation modified erythrocytes surface and protein-lipid bilayer showed marked changes. The significance of oxidative damage of biophase under conditions of acute pain syndrome for analgesics effective pharmacodynamics and pharmacokinetics realization is under consideration.

  14. Does anodal transcranial direct current stimulation modulate sensory perception and pain? A meta-analysis study.

    Science.gov (United States)

    Vaseghi, B; Zoghi, M; Jaberzadeh, S

    2014-09-01

    The primary aim of this systematic review was to evaluate the effects of anodal transcranial direct current stimulation (a-tDCS) on sensory (STh) and pain thresholds (PTh) in healthy individuals and pain levels (PL) in patients with chronic pain. Electronic databases were searched for a-tDCS studies. Methodological quality was examined using the PEDro and Downs and Black (D&B) assessment tools. a-tDCS of the primary motor cortex (M1) increases both STh (P<0.005, with the effect size of 22.19%) and PTh (P<0.001, effect size of 19.28%). In addition, STh was increased by a-tDCS of the primary sensory cortex (S1) (P<0.05 with an effect size of 4.34). Likewise, PL decreased significantly in the patient group following application of a-tDCS to both the M1 and dorsolateral prefrontal cortex (DLPFC). The average decrease in visual analogue score was 14.9% and 19.3% after applying a-tDCS on the M1 and DLPFC. Moreover, meta-analysis showed that in all subgroups (except a-tDCS of S1) active a-tDCS and sham stimulation produced significant differences. This review provides evidence for the effectiveness of a-tDCS in increasing STh/PTh in healthy group and decreasing PL in patients. However, due to small sample sizes in the included studies, our results should be interpreted cautiously. Given the level of blinding did not considered in inclusion criteria, the result of current study should be interpreted with caution. Site of stimulation should have a differential effect over pain relief. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  15. The role of spinal cord vanilloid (TRPV1) receptors in pain modulation

    Czech Academy of Sciences Publication Activity Database

    Špicarová, Diana; Paleček, Jiří

    2008-01-01

    Roč. 57, Suppl.3 (2008), S69-S77 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/06/1115; GA ČR(CZ) GA304/08/0256; GA MŠk(CZ) LC554 Grant - others:EC(XE) LSH-CT-2004-511978 Institutional research plan: CEZ:AV0Z50110509 Keywords : pain * TRPV1 * spinal cord Subject RIV: FH - Neurology Impact factor: 1.653, year: 2008

  16. Central Sensitization Is Modulated Following Trigger Point Anesthetization in Patients with Chronic Pain from Whiplash Trauma. A Double-Blind, Placebo-Controlled, Crossover Study.

    Science.gov (United States)

    Nystrom, N Ake; Freeman, Michael D

    2018-01-01

    Central sensitization (CS) with low peripheral pain thresholds (PPTs) is a common finding among patients with chronic pain after whiplash (CPWI). While it has been proposed that myofascial myofascial trigger points (MTrPs) may act as modulators of central sensitization, previously reported findings are conflicting and inconclusive. The present study was designed to investigate immediate responsiveness of CS to alterations in nociceptive input. Controlled, double-blind, cross-over. Thirty-one patients with chronic pain (trapezius myalgia) and CS after whiplash. Participants were referred by randomization to group A for injection of a single peripheral pain generator (MTrP or other discrete tender point) with local anesthetic or to group B for sham injection and cross-over. Documentation of PPT (Algometer), maximum jaw opening (caliper), and grip strength (Vigorimeter), as well as subjective overall pain (visual analog scale [VAS]), was made before and after each intervention. Statistical analysis of data (Student's t test, analysis of variance) confirmed that peripheral pain thresholds were significantly higher and maximum jaw opening significantly greater after anesthetizing a focal pain generator in the trapezius, but not after a sham injection. In contrast with the objective variables, subjective generalized pain improved (VAS) after not only an injection of local anesthetic, but also, and to a similar extent, after a sham injection. CS, as expressed by lowered PPT, is a rapidly adjusting physiological response to nociceptive stimuli in some patients with chronic pain after whiplash. PPT are likely modulated by myofascial tender points in selected patients with CS. With reference to the present findings, surgical ablation of MTrPs is discussed as a potential treatment modality for CS. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  17. Standard Test Method for Electrical Performance of Concentrator Terrestrial Photovoltaic Modules and Systems Under Natural Sunlight

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2009-01-01

    1.1 This test method covers the determination of the electrical performance of photovoltaic concentrator modules and systems under natural sunlight using a normal incidence pyrheliometer. 1.2 The test method is limited to module assemblies and systems where the geometric concentration ratio specified by the manufacturer is greater than 5. 1.3 This test method applies to concentrators that use passive cooling where the cell temperature is related to the air temperature. 1.4 Measurements under a variety of conditions are allowed; results are reported under a select set of concentrator reporting conditions to facilitate comparison of results. 1.5 This test method applies only to concentrator terrestrial modules and systems. 1.6 This test method assumes that the module or system electrical performance characteristics do not change during the period of test. 1.7 The performance rating determined by this test method applies only at the period of the test, and implies no past or future performance level. 1.8...

  18. Decreased pain perception by unconscious emotional pictures

    Directory of Open Access Journals (Sweden)

    Irene Peláez

    2016-10-01

    Full Text Available Pain perception arises from a complex interaction between a nociceptive stimulus and different emotional and cognitive factors, which appear to be mediated by both automatic and controlled systems. Previous evidence has shown that whereas conscious processing of unpleasant stimuli enhances pain perception, emotional influences on pain under unaware conditions are much less known. The aim of the present study was to investigate the modulation of pain perception by unconscious emotional pictures through an emotional masking paradigm. Two kinds of both somatosensory (painful and non-painful and emotional stimulation (negative and neutral pictures were employed. Fifty pain-free participants were asked to rate the perception of pain they were feeling in response to laser-induced somatosensory stimuli as faster as they can. Data from pain intensity and reaction times were measured. Statistical analyses revealed a significant effect for the interaction between pain and emotional stimulation, but surprisingly this relationship was opposite to expected. In particular, lower pain intensity scores and longer reaction times were found in response to negative images being strengthened this effect for painful stimulation. Present findings suggest a clear pain perception modulation by unconscious emotional contexts. Attentional capture mechanisms triggered by unaware negative stimulation could explain this phenomenon leading to a withdrawal of processing resources from pain.

  19. Analgesic effect of ADX71441, a positive allosteric modulator (PAM) of GABAB receptor in a rat model of bladder pain.

    Science.gov (United States)

    Kannampalli, Pradeep; Poli, Sonia-Maria; Boléa, Christelle; Sengupta, Jyoti N

    2017-11-01

    Therapeutic use of GABA B receptor agonists for conditions like chronic abdominal pain, overactive bladder (OAB) and gastroesophageal reflux disease (GERD) is severely affected by poor blood-brain barrier permeability and potential side effects. ADX71441 is a novel positive allosteric modulator (PAM) of the GABA B receptor that has shown encouraging results in pre-clinical models of anxiety, pain, OAB and alcohol addiction. The present study investigates the analgesic effect of ADX71441 to noxious stimulation of the urinary bladder and colon in rats. In female Sprague-Dawley rats, systemic (i.p), but not intrathecal (i.t), administration of ADX71441 produced a dose-dependent decrease in viscero-motor response (VMR) to graded urinary bladder distension (UBD) and colorectal distension (CRD). Additionally, intra-cerebroventricular (i.c.v.) administration of ADX71441 significantly decreased the VMRs to noxious UBD. In electrophysiology experiments, the drug did not attenuate the responses of UBD-sensitive pelvic nerve afferent (PNA) fibers to UBD. In contrast, ADX71441 significantly decreased the responses of UBD-responsive lumbosacral (LS) spinal neurons in spinal intact rats. However, ADX71441 did not attenuate these LS neurons in cervical (C1-C2) spinal transected rats. During cystometrogram (CMG) recordings, ADX71441 (i.p.) significantly decreased the VMR to slow infusion without affecting the number of voiding contraction. These results indicate that ADX71441 modulate bladder nociception via its effect at the supra-spinal sites without affecting the normal bladder motility and micturition reflex in naïve adult rats. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain

    Directory of Open Access Journals (Sweden)

    Ellis Connie L

    2010-03-01

    Full Text Available Abstract Background Despite the frequency of diabetes mellitus and its relationship to diabetic peripheral neuropathy (DPN and neuropathic pain (NeP, our understanding of underlying mechanisms leading to chronic pain in diabetes remains poor. Recent evidence has demonstated a prominent role of microglial cells in neuropathic pain states. One potential therapeutic option gaining clinical acceptance is the cannabinoids, for which cannabinoid receptors (CB are expressed on neurons and microglia. We studied the accumulation and activation of spinal and thalamic microglia in streptozotocin (STZ-diabetic CD1 mice and the impact of cannabinoid receptor agonism/antagonism during the development of a chronic NeP state. We provided either intranasal or intraperitoneal cannabinoid agonists/antagonists at multiple doses both at the initiation of diabetes as well as after establishment of diabetes and its related NeP state. Results Tactile allodynia and thermal hypersensitivity were observed over 8 months in diabetic mice without intervention. Microglial density increases were seen in the dorsal spinal cord and in thalamic nuclei and were accompanied by elevation of phosphorylated p38 MAPK, a marker of microglial activation. When initiated coincidentally with diabetes, moderate-high doses of intranasal cannabidiol (cannaboid receptor 2 agonist and intraperitoneal cannabidiol attenuated the development of an NeP state, even after their discontinuation and without modification of the diabetic state. Cannabidiol was also associated with restriction in elevation of microglial density in the dorsal spinal cord and elevation in phosphorylated p38 MAPK. When initiated in an established DPN NeP state, both CB1 and CB2 agonists demonstrated an antinociceptive effect until their discontinuation. There were no pronociceptive effects demonstated for either CB1 or CB2 antagonists. Conclusions The prevention of microglial accumulation and activation in the dorsal spinal

  1. Amplitude modulation of sound from wind turbines under various meteorological conditions.

    Science.gov (United States)

    Larsson, Conny; Öhlund, Olof

    2014-01-01

    Wind turbine (WT) sound annoys some people even though the sound levels are relatively low. This could be because of the amplitude modulated "swishing" characteristic of the turbine sound, which is not taken into account by standard procedures for measuring average sound levels. Studies of sound immission from WTs were conducted continually between 19 August 2011 and 19 August 2012 at two sites in Sweden. A method for quantifying the degree and strength of amplitude modulation (AM) is introduced here. The method reveals that AM at the immission points occur under specific meteorological conditions. For WT sound immission, the wind direction and sound speed gradient are crucial for the occurrence of AM. Interference between two or more WTs could probably enhance AM. The mechanisms by which WT sound is amplitude modulated are not fully understood.

  2. TAFA4, a Chemokine-like Protein, Modulates Injury-Induced Mechanical and Chemical Pain Hypersensitivity in Mice

    Directory of Open Access Journals (Sweden)

    Marie-Claire Delfini

    2013-10-01

    Full Text Available C-low-threshold mechanoreceptors (C-LTMRs are unique among C-unmyelinated primary sensory neurons. These neurons convey two opposite aspects of touch sensation: a sensation of pleasantness, and a sensation of injury-induced mechanical pain. Here, we show that TAFA4 is a specific marker of C-LTMRs. Genetic labeling in combination with electrophysiological recordings show that TAFA4+ neurons have intrinsic properties of mechano-nociceptors. TAFA4-null mice exhibit enhanced mechanical and chemical hypersensitivity following inflammation and nerve injury as well as increased excitability of spinal cord lamina IIi neurons, which could be reversed by intrathecal or bath application of recombinant TAFA4 protein. In wild-type C57/Bl6 mice, intrathecal administration of TAFA4 strongly reversed carrageenan-induced mechanical hypersensitivity, suggesting a potent analgesic role of TAFA4 in pain relief. Our data provide insights into how C-LTMR-derived TAFA4 modulates neuronal excitability and controls the threshold of somatic sensation.

  3. Intra-subunit flexibility underlies activation and allosteric modulation of neuronal nicotinic acetylcholine receptors.

    Science.gov (United States)

    Chrisman, Paul A; Podair, Julie I; Jobe, Emily M; Levandoski, Mark M

    2014-04-01

    Allosteric modulation is a general feature of nicotinic acetylcholine receptors, yet the structural components and movements important for conversions among functional states are not well understood. In this study, we examine the communication between the binding sites for agonist and the modulator morantel (Mor) of neuronal α3β2 receptors, measuring evoked currents of receptors expressed in Xenopus oocytes with the two-electrode voltage-clamp method. We hypothesized that movement along an interface of β sheets connecting the agonist and modulator sites is necessary for allosteric modulation. To address this, we created pairs of substituted cysteines that span the cleft formed where the outer β sheet meets the β sheet constituting the (-)-face of the α3 subunit; the three pairs were L158C-A179C, L158C-G181C and L158C-K183C. Employing a disulfide trapping approach in which bonds are formed between neighboring cysteines under oxidation conditions, we found that oxidation treatments decreased the amplitude of currents evoked by either the agonist (ACh) or co-applied agonist and modulator (ACh + Mor), by as much as 51%, consistent with the introduced bond decreasing channel efficacy. Reduction treatment increased evoked currents up to 89%. The magnitude of the oxidation effects depended on whether agonists were present during oxidation and on the cysteine pair. Additionally, the cysteine mutations themselves decreased Mor potentiation, implicating these residues in modulation. Our findings suggest that these β sheets in the α3 subunit move with respect to each other during activation and modulation, and the residues studied highlight the contribution of this intramolecular allosteric pathway to receptor function. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Eugenol reduces acute pain in mice by modulating the glutamatergic and tumor necrosis factor alpha (TNF-α) pathways.

    Science.gov (United States)

    Dal Bó, Wladmir; Luiz, Ana Paula; Martins, Daniel F; Mazzardo-Martins, Leidiane; Santos, Adair R S

    2013-10-01

    Eugenol is utilized together with zinc oxide in odontological clinical for the cementation of temporary prostheses and the temporary restoration of teeth and cavities. This work explored the antinociceptive effects of the eugenol in different models of acute pain in mice and investigated its possible modulation of the inhibitory (opioid) and excitatory (glutamatergic and pro-inflammatory cytokines) pathways of nociceptive signaling. The administration of eugenol (3-300 mg/kg, p.o., 60 min or i.p., 30 min) inhibited 82 ± 10% and 90 ± 6% of the acetic acid-induced nociception, with ID₅₀ values of 51.3 and 50.2 mg/kg, respectively. In the glutamate test, eugenol (0.3-100 mg/kg, i.p.) reduced the response behavior by 62 ± 5% with an ID₅₀ of 5.6 mg/kg. In addition, the antinociceptive effect of eugenol (10 mg/kg, i.p.) in the glutamate test was prevented by the i.p. treatment for mice with naloxone. The pretreatment of mice with eugenol (10 mg/kg, i.p.) was able to inhibit the nociception induced by the intrathecal (i.t.) injection of glutamate (37 ± 9%), kainic (acid kainite) (41 ± 12%), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (55 ± 5%), and substance P (SP) (39 ± 8%). Furthermore, eugenol (10 mg/kg, i.p.) also inhibited biting induced by tumor necrosis factor alpha (TNF-α, 65 ± 8%). These results extend our current knowledge of eugenol and confirm that it promotes significant antinociception against different mouse models of acute pain. The mechanism of action appears to involve the modulation of the opioid system and glutamatergic receptors (i.e., kainate and AMPA), and the inhibition of TNF-α. Thus, eugenol could represent an important compound in the treatment for acute pain. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.

  5. Effects of the carrier frequency of interferential current on pain modulation and central hypersensitivity in people with chronic nonspecific low back pain: A randomized placebo-controlled trial.

    Science.gov (United States)

    Corrêa, J B; Costa, L O P; Oliveira, N T B; Lima, W P; Sluka, K A; Liebano, R E

    2016-11-01

    Interferential current (IFC) is commonly used for pain relief, but the effects of carrier frequency of the current and its action on pain mechanisms remain unclear. This randomized placebo-controlled trial tested the effects of IFC in people with chronic nonspecific low back pain. One hundred and fifty participants were randomly allocated into three groups: 1 kHz, 4 kHz and placebo. The primary outcomes were pain intensity at rest in the first session (immediate effect of the IFC), after 12 sessions, 4 months after randomization (follow-up) and during movement (first and last session). The secondary outcomes were disability, global perceived effect, functional performance, discomfort caused by the IFC, use of analgesics and physiological measures of pain. Only during the first session, there was a significant decrease in pain intensity in the active groups. However, there were no differences in the improvement of pain at rest or during movement in the active groups compared to the placebo group in the remaining sessions. The frequency use of analgesics was significantly decreased in the active groups. For pain physiology measures, there was a significant increase in pressure pain thresholds in both active groups compared to the placebo group and a reduction in the temporal summation in the 1 kHz group compared to the other groups. These results suggest that although the IFC has changed some physiological mechanisms of pain and showed decrease frequency use of pain medication, there was no change in the primary aim, pain intensity. WHAT DOES THIS STUDY ADD?: The interferential current (IFC) presented advantages in the physiological measures of pain and showed decrease frequency use of pain medication. Future studies should investigate analgesic intake with IFC treatment. © 2016 European Pain Federation - EFIC®.

  6. Mechanisms underlying the noradrenergic modulation of longitudinal coordination during swimming in Xenopus laevis tadpoles

    DEFF Research Database (Denmark)

    Merrywest, Simon D; McDearmid, Jonathan R; Kjaerulff, Ole

    2003-01-01

    Noradrenaline (NA) is a potent modulator of locomotion in many vertebrate nervous systems. When Xenopus tadpoles swim, waves of motor neuron activity alternate across the body and propagate along it with a brief rostro-caudal delay (RC-delay) between segments. We have now investigated the mechani......, will preferentially facilitate rebound firing in caudal neurons, advancing their firing relative to more rostral neurons, whilst additionally increasing the networks ability to sustain the longer cycle periods under NA....

  7. The Effect of Subcutaneous Ketamine Infiltration on Postoperative Pain in Elective Cesarean Section under Spinal Anesthesia

    Directory of Open Access Journals (Sweden)

    N. Manouchehrian

    2015-01-01

    Full Text Available Introduction & Objective: Appropriate analgesia after cesarean section helps women feel more comfortable and increase the mobility of the mother's and also their ability to take better care of their newborns. The purpose of this study was to investigate the effects of subcutaneous infiltration of ketamine on postoperative pain reduction and hemodynamic status of patients after elective cesarean section. Materials & Methods: This study was designed as a double blinded prospective, randomized clinical trial and 60 cases of women undergoing elective cesarean section under spinal anes-thesia were randomly assigned into two groups. For 30 cases in the ketamine group, infiltra-tion of subcutaneous ketamine 0.5 mg / kg was administered after closure of surgical inci-sion. 30 patients in the placebo group received subcutaneous infiltration of saline. During the patient's recovery time and after transferring to the ward, the VAS of pain and vital signs were continuously assessed. if VAS ? 3, 100 mg diclofenac suppository was administered and if there were no response, 30 mg intravenous pethidine was also administered. Prescribed number of suppositories and pethidine dosage were compared. The complications, such as hallucination, nystagmus, nausea, vomiting and drowsiness in patients were also recorded and compared. Statistical analysis was performed by SPSS16 software and ?2 and t-test. P< 0.05 was considered statistically significant in all of the cases. Results: In the course of systolic blood pressure, heart rate and arterial blood oxygen satura-tion during the first 24 hours, no significant differences were mentioned between the two groups. At the time of arrival to the recovery room and 30 minutes later, the mean VAS was not significantly different in the groups. However, the mean VAS at 1, 2 , 4 , 6 , 8 and 12 hours after surgery were significantly lower in the ketamine group (0.61±059 than in the sa-line group (3.37±096 (P<0.001. The mean

  8. The efficacy of playing a virtual reality game in modulating pain for children with acute burn injuries: a randomized controlled trial [ISRCTN87413556].

    Science.gov (United States)

    Das, Debashish A; Grimmer, Karen A; Sparnon, Anthony L; McRae, Sarah E; Thomas, Bruce H

    2005-03-03

    The management of burn injuries is reported as painful, distressing and a cause of anxiety in children and their parents. Child's and parents' pain and anxiety, often contributes to extended time required for burns management procedures, in particular the process of changing dressings. The traditional method of pharmacologic analgesia is often insufficient to cover the burnt child's pain, and it can have deleterious side effects 12. Intervention with Virtual Reality (VR) games is based on distraction or interruption in the way current thoughts, including pain, are processed by the brain. Research on adults supports the hypothesis that virtual reality has a positive influence on burns pain modulation. This study investigates whether playing a virtual reality game, decreases procedural pain in children aged 5-18 years with acute burn injuries. The paper reports on the findings of a pilot study, a randomised trial, in which seven children acted as their own controls though a series of 11 trials. Outcomes were pain measured using the self-report Faces Scale and findings of interviews with parent/carer and nurses. The average pain scores (from the Faces Scale) for pharmacological analgesia only was, 4.1 (SD 2.9), while VR coupled with pharmacological analgesia, the average pain score was 1.3 (SD 1.8) The study provides strong evidence supporting VR based games in providing analgesia with minimal side effects and little impact on the physical hospital environment, as well as its reusability and versatility, suggesting another option in the management of children's acute pain.

  9. The efficacy of playing a virtual reality game in modulating pain for children with acute burn injuries: A randomized controlled trial [ISRCTN87413556

    Directory of Open Access Journals (Sweden)

    McRae Sarah E

    2005-03-01

    Full Text Available Abstract Background The management of burn injuries is reported as painful, distressing and a cause of anxiety in children and their parents. Child's and parents' pain and anxiety, often contributes to extended time required for burns management procedures, in particular the process of changing dressings. The traditional method of pharmacologic analgesia is often insufficient to cover the burnt child's pain, and it can have deleterious side effects 12. Intervention with Virtual Reality (VR games is based on distraction or interruption in the way current thoughts, including pain, are processed by the brain. Research on adults supports the hypothesis that virtual reality has a positive influence on burns pain modulation. Methods This study investigates whether playing a virtual reality game, decreases procedural pain in children aged 5–18 years with acute burn injuries. The paper reports on the findings of a pilot study, a randomised trial, in which seven children acted as their own controls though a series of 11 trials. Outcomes were pain measured using the self-report Faces Scale and findings of interviews with parent/carer and nurses. Results The average pain scores (from the Faces Scale for pharmacological analgesia only was, 4.1 (SD 2.9, while VR coupled with pharmacological analgesia, the average pain score was 1.3 (SD 1.8 Conclusion The study provides strong evidence supporting VR based games in providing analgesia with minimal side effects and little impact on the physical hospital environment, as well as its reusability and versatility, suggesting another option in the management of children's acute pain.

  10. Decision framework of photovoltaic module selection under interval-valued intuitionistic fuzzy environment

    International Nuclear Information System (INIS)

    Long, Shengping; Geng, Shuai

    2015-01-01

    Highlights: • The evaluation index system is set by the engineering and supply chain perspectives. • The interval-valued intuitionistic fuzzy set (IVIFS) to express the performances. • The IVIFS entropy weight method is applied to improve the objectivity of weights. - Abstract: The selection of appropriate photovoltaic module is of extremely high importance for the solar power station project; however the comprehensive problem of evaluation index system, the information loss problem and the lack-objectivity problem in the selection process will decrease the reasonability of the selection result. The innovation points of this paper are as follows: first, the comprehensive evaluation index system of photovoltaic module is established from the engineering management and supply chain management perspectives to solve the comprehensive problem; second, the interval-valued intuitionistic fuzzy set (IVIFS) are introduced into the photovoltaic modules selection process to express the alternatives’ performances to solve the information loss problem; third, the IVIFS entropy weight method is applied to improve the objectivity of the criteria’s weights. According to the aforementioned solutions, the decision framework of photovoltaic module selection under interval-valued intuitionistic fuzzy environment are established and used in a case study to demonstrate its effectiveness. Therefore, from the theoretical modeling and empirical demonstration, the decision framework proposed in this paper can effectively handle such a complicated problem and lead to an outstanding result.

  11. Short-term test-retest-reliability of conditioned pain modulation using the cold-heat-pain method in healthy subjects and its correlation to parameters of standardized quantitative sensory testing.

    Science.gov (United States)

    Gehling, Julia; Mainka, Tina; Vollert, Jan; Pogatzki-Zahn, Esther M; Maier, Christoph; Enax-Krumova, Elena K

    2016-08-05

    Conditioned Pain Modulation (CPM) is often used to assess human descending pain inhibition. Nine different studies on the test-retest-reliability of different CPM paradigms have been published, but none of them has investigated the commonly used heat-cold-pain method. The results vary widely and therefore, reliability measures cannot be extrapolated from one CPM paradigm to another. Aim of the present study was to analyse the test-retest-reliability of the common heat-cold-pain method and its correlation to pain thresholds. We tested the short-term test-retest-reliability within 40 ± 19.9 h using a cold-water immersion (10 °C, left hand) as conditioning stimulus (CS) and heat pain (43-49 °C, pain intensity 60 ± 5 on the 101-point numeric rating scale, right forearm) as test stimulus (TS) in 25 healthy right-handed subjects (12females, 31.6 ± 14.1 years). The TS was applied 30s before (TSbefore), during (TSduring) and after (TSafter) the 60s CS. The difference between the pain ratings for TSbefore and TSduring represents the early CPM-effect, between TSbefore and TSafter the late CPM-effect. Quantitative sensory testing (QST, DFNS protocol) was performed on both sessions before the CPM assessment. paired t-tests, Intraclass correlation coefficient (ICC), standard error of measurement (SEM), smallest real difference (SRD), Pearson's correlation, Bland-Altman analysis, significance level p test-retest-reliability of the early CPM-effect using the heat-cold-pain method in healthy subjects achieved satisfying results in terms of the ICC. The SRD of the early CPM effect showed that an individual change of > 20 NRS can be attributed to a real change rather than chance. The late CPM-effect was weaker and not reliable.

  12. Signaling mechanism underlying the histamine-modulated action of hypoglossal motoneurons.

    Science.gov (United States)

    Liu, Zi-Long; Wu, Xu; Luo, Yan-Jia; Wang, Lu; Qu, Wei-Min; Li, Shan-Qun; Huang, Zhi-Li

    2016-04-01

    Histamine, an important modulator of the arousal states of the central nervous system, has been reported to contribute an excitatory drive at the hypoglossal motor nucleus to the genioglossus (GG) muscle, which is involved in the pathogenesis of obstructive sleep apnea. However, the effect of histamine on hypoglossal motoneurons (HMNs) and the underlying signaling mechanisms have remained elusive. Here, whole-cell patch-clamp recordings were conducted using neonatal rat brain sections, which showed that histamine excited HMNs with an inward current under voltage-clamp and a depolarization membrane potential under current-clamp via histamine H1 receptors (H1Rs). The phospholipase C inhibitor U-73122 blocked H1Rs-mediated excitatory effects, but protein kinase A inhibitor and protein kinase C inhibitor did not, indicating that the signal transduction cascades underlying the excitatory action of histamine on HMNs were H1R/Gq/11 /phospholipase C/inositol-1,4,5-trisphosphate (IP3). The effects of histamine were also dependent on extracellular Na(+) and intracellular Ca(2+), which took place via activation of Na(+)-Ca(2+) exchangers. These results identify the signaling molecules associated with the regulatory effect of histamine on HMNs. The findings of this study may provide new insights into therapeutic approaches in obstructive sleep apnea. We proposed the post-synaptic mechanisms underlying the modulation effect of histamine on hypoglossal motoneuron. Histamine activates the H1Rs via PLC and IP3, increases Ca(2+) releases from intracellular stores, promotes Na(+) influx and Ca(2+) efflux via the NCXs, and then produces an inward current and depolarizes the neurons. Histamine modulates the excitability of HMNs with other neuromodulators, such as noradrenaline, serotonin and orexin. We think that these findings should provide an important new direction for drug development for the treatment of obstructive sleep apnea. © 2016 International Society for Neurochemistry.

  13. Shoulder tip pain: an under-reported complication of ventriculoperitoneal shunt.

    LENUS (Irish Health Repository)

    Lim, C

    2012-02-03

    Ventriculoperitoneal (VP) shunt insertion is the commonest form of treatment for hydrocephalus. Shoulder tip pain after VP shunt insertion is unusual and has only recently been reported. We present a case of excruciating shoulder tip pain due to diaphragmatic irritation after VP shunt insertion.

  14. Unexpected Behavior of Some Nitric Oxide Modulators under Cadmium Excess in Plant Tissue

    Science.gov (United States)

    Kováčik, Jozef; Babula, Petr; Klejdus, Bořivoj; Hedbavny, Josef; Jarošová, Markéta

    2014-01-01

    Various nitric oxide modulators (NO donors - SNP, GSNO, DEA NONOate and scavengers – PTIO, cPTIO) were tested to highlight the role of NO under Cd excess in various ontogenetic stages of chamomile (Matricaria chamomilla). Surprisingly, compared to Cd alone, SNP and PTIO elevated Cd uptake (confirmed also by PhenGreen staining) but depleted glutathione (partially ascorbic acid) and phytochelatins PC2 and PC3 in both older plants (cultured hydroponically) and seedlings (cultured in deionised water). Despite these anomalous impacts, fluorescence staining of NO and ROS confirmed predictable assumptions and revealed reciprocal changes (decrease in NO but increase in ROS after PTIO addition and the opposite after SNP application). Subsequent tests using alternative modulators and seedlings confirmed changes to NO and ROS after application of GSNO and DEA NONOate as mentioned above for SNP while cPTIO altered only NO level (depletion). On the contrary to SNP and PTIO, GSNO, DEA NONOate and cPTIO did not elevate Cd content and phytochelatins (PC2, PC3) were rather elevated. These data provide evidence that various NO modulators are useful in terms of NO and ROS manipulation but interactions with intact plants affect metal uptake and must therefore be used with caution. In this view, cPTIO and DEA NONOate revealed the less pronounced side impacts and are recommended as suitable NO scavenger/donor in plant physiological studies under Cd excess. PMID:24626462

  15. [Dialogues with nurses about oncologic pain assessment of patients under palliative care].

    Science.gov (United States)

    Waterkemper, Roberta; Reibnitz, Kenya Schmidt; Monticelli, Marisa

    2010-01-01

    It is an experience report developed next to nurses of a public hospital of Florianópolis-SC, about pain measurement of cancer patient in palliative cares. A total of six nurses had participated of six meeting distributed at three educative moments of this practical. The analysis of undertaken dialogue evidenced that, for the nurses, measurable and objective data are not only enough to measure pain. According to them, it is imperative consider biopsicosociais aspects, valuing integrally the pain that the patient relates. The concluding nurses detach that she has necessity to construct a pain measurement systematization to allow strengthens the importance of pain control to base the practical one, make possible the register of information and the continued education.

  16. The Biochemical Origin of Pain: The origin of all Pain is Inflammation and the Inflammatory Response. PART 2 of 3 –Inflammatory Profile of Pain Syndromes

    Science.gov (United States)

    2009-01-01

    Every pain syndrome has an inflammatory profile consisting of the inflammatory mediators that are present in the pain syndrome. The inflammatory profile may have variations from one person to another and may have variations in the same person at different times. The key to treatment of Pain Syndromes is an understanding of their inflammatory profile. Pain syndromes may be treated medically or surgically. The goal should be inhibition or suppression of production of the inflammatory mediators and inhibition, suppression or modulation of neuronal afferent and efferent (motor) transmission. A successful outcome is one that results in less inflammation and thus less pain. We hereby describe the inflammatory profile for several pain syndromes including arthritis, back pain, neck pain, fibromyalgia, interstitial cystitis, migraine, neuropathic pain, complex regional pain syndrome / reflex sympathetic dystrophy (CRPS/RSD), bursitis, shoulder pain and vulvodynia. These profiles are derived from basic science and clinical research performed in the past by numerous investigators and will be updated in the future by new technologies such as magnetic resonance spectroscopy. Our unifying theory or law of pain states: The origin of all pain is inflammation and the inflammatory response. The biochemical mediators of inflammation include cytokines, neuropeptides, growth factors and neurotransmitters. Irrespective of the type of pain whether it is acute or chronic pain, peripheral or central pain, nociceptive or neuropathic pain, the underlying origin is inflammation and the inflammatory response. Activation of pain receptors, transmission and modulation of pain signals, neuro plasticity and central sensitization are all one continuum of inflammation and the inflammatory response. Irrespective of the characteristic of the pain, whether it is sharp, dull, aching, burning, stabbing, numbing or tingling, all pain arise from inflammation and the inflammatory response. We are proposing

  17. Performance evaluation of the DCMD desalination process under bench scale and large scale module operating conditions

    KAUST Repository

    Francis, Lijo

    2014-04-01

    The flux performance of different hydrophobic microporous flat sheet commercial membranes made of poly tetrafluoroethylene (PTFE) and poly propylene (PP) was tested for Red Sea water desalination using the direct contact membrane distillation (DCMD) process, under bench scale (high δT) and large scale module (low δT) operating conditions. Membranes were characterized for their surface morphology, water contact angle, thickness, porosity, pore size and pore size distribution. The DCMD process performance was optimized using a locally designed and fabricated module aiming to maximize the flux at different levels of operating parameters, mainly feed water and coolant inlet temperatures at different temperature differences across the membrane (δT). Water vapor flux of 88.8kg/m2h was obtained using a PTFE membrane at high δT (60°C). In addition, the flux performance was compared to the first generation of a new locally synthesized and fabricated membrane made of a different class of polymer under the same conditions. A total salt rejection of 99.99% and boron rejection of 99.41% were achieved under extreme operating conditions. On the other hand, a detailed water characterization revealed that low molecular weight non-ionic molecules (ppb level) were transported with the water vapor molecules through the membrane structure. The membrane which provided the highest flux was then tested under large scale module operating conditions. The average flux of the latter study (low δT) was found to be eight times lower than that of the bench scale (high δT) operating conditions.

  18. THE THIOREDOXIN SYSTEM IN REGULATING MCF-7 CELL PROLIFERATION UNDER REDOX STATUS MODULATION

    Directory of Open Access Journals (Sweden)

    E. A. Stepovaya

    2016-01-01

    Full Text Available Introduction. Despite the available data on tumor cell functioning under the conditions of free radical-mediated oxidation, the mechanisms of redox regulation, cell proliferation management and apoptosis avoidance remain understudied.The objective of the study was to identify the role of the thioredoxin system in regulating MCF-7 breast cancer cell proliferation under redox status modulation with 1.4-dithioerythritol.Material and methods. The studies were conducted on the MCF-7 breast cancer cell line, grown in adherent cell culture. Cell redox status was modulated with5 mM N-ethylmaleimide – an SH group and peptide inhibitor and5 mM 1.4-dithioerythritol – a thiol group protector. The cell cycle was evaluated by flow cytometry, the same technique was used to measure the reactive oxygen species concentration. The levels of reduced and oxidized glutathione and the activity of thioredoxin reductase were identified by spectrophotometry. The intracellular concentrations of thioredoxin, cyclin E and cyclin-dependent kinase 2 were determined by Western blot analysis.Results and discussion. The essential role of the thioredoxin system in regulating MCF-7 breast cancer cell proliferation was exhibited. S-phase arrest under the effect of N-ethylmaleimide and G0/G1-phase arrest under the effect of 1.4-dithioerythritol are associated with the changes in the activity of redox-sensitive protein complexes (cyclins and cyclin-dependent kinases that regulate cell proliferation.Conclusion. Redoxdependent modulation of proliferation regulating intracellular protein activity occurs due to the thioredoxin system. This is a promising research area for seeking molecular targets of breast cell malignization. 

  19. Dose escalation by image-guided intensity-modulated radiotherapy leads to an increase in pain relief for spinal metastases: a comparison study with a regimen of 30 Gy in 10 fractions.

    Science.gov (United States)

    He, Jinlan; Xiao, Jianghong; Peng, Xingchen; Duan, Baofeng; Li, Yan; Ai, Ping; Yao, Min; Chen, Nianyong

    2017-12-22

    Under the existing condition that the optimum radiotherapy regimen for spinal metastases is controversial, this study investigates the benefits of dose escalation by image-guided intensity-modulated radiotherapy (IG-IMRT) with 60-66 Gy in 20-30 fractions for spinal metastases. In the dose-escalation group, each D50 of planning gross tumor volume (PGTV) was above 60 Gy and each Dmax of spinal cord planning organ at risk volume (PRV) was below 48 Gy. The median biological effective dose (BED) of Dmax of spinal cord was lower in the dose-escalation group compared with that in the 30-Gy group (69.70 Gy vs. 83.16 Gy, p pain responses were better in the dose-escalation group than those in the 30-Gy group ( p = 0.005 and p = 0.024), and the complete pain relief rates were respectively 73.69% and 34.29% ( p = 0.006), 73.69% and 41.38% ( p = 0.028) in two compared groups. In the dose-escalation group, there is a trend of a longer duration of pain relief, a longer overall survival and a lower incidence of acute radiation toxicities. No late radiation toxicities were observed in both groups. Dosimetric parameters and clinical outcomes, including pain response, duration of pain relief, radiation toxicities and overall survival, were compared among twenty-five metastatic spinal lesions irradiated with the dose-escalation regimen and among forty-four lesions treated with the 30-Gy regimen. Conventionally-fractionated IG-IMRT for spinal metastases could escalate dose to the vertebral lesions while sparing the spinal cord, achieving a better pain relief without increasing radiation complications.

  20. Quality of life under oxycodone/naloxone, oxycodone, or morphine treatment for chronic low back pain in routine clinical practice

    Directory of Open Access Journals (Sweden)

    Ueberall MA

    2016-02-01

    Full Text Available Michael A Ueberall,1 Alice Eberhardt,2 Gerhard HH Mueller-Schwefe3 1Institute for Neurological Sciences, Nuernberg, Germany; 2Mundipharma GmbH, Limburg, Germany; 3Interdisciplinary Center for Pain and Palliative Care Medicine, Goeppingen, Germany Objective: To compare the quality of life of patients with moderate-to-severe chronic low back pain under treatment with the WHO-step III opioids oxycodone/naloxone, oxycodone, or morphine in routine clinical practice. Study design: Prospective, 12-week, randomized, open-label, blinded end-point study in 88 medical centers in Germany. Patients and methods: A total of 901 patients requiring around-the-clock pain treatment with a WHO-step III opioid were randomized to either morphine, oxycodone, or oxycodone/naloxone (1:1:1. Changes from baseline to week 12 in quality of life were assessed using different validated tools (EuroQoL-5 Dimensions [EQ-5D], Short Form 12 [SF-12], quality of life impairment by pain inventory [QLIP]. Results: EQ-5D weighted index scores significantly improved over the 12-week treatment period under all three opioids (P<0.001 with significantly greater improvements under oxycodone/naloxone (65.2% vs 49.6% for oxycodone and 48.2% for morphine, P<0.001. The proportion of patients without EQ-5D complaints was also significantly higher under oxycodone/naloxone (P<0.001. Although quality of life ratings with the QLIP inventory showed significant improvements in all the three treatment arms, improvements were significantly higher under oxycodone/naloxone than under oxycodone and morphine (P<0.001: 90.7% of all oxycodone/naloxone patients achieved ≥30% improvements in quality of life, 72.8% had ≥50%, and 33.2% ≥70% improvements. Similarly, both physical and mental SF-12 component scores showed significantly greater improvements under oxycodone/naloxone with both scores close to the German population norm after 12 weeks. Conclusion: Treatment with morphine, oxycodone, or oxycodone

  1. Manual small incision cataract surgery under topical anesthesia with intracameral lignocaine: Study on pain evaluation and surgical outcome

    Directory of Open Access Journals (Sweden)

    Gupta Sanjiv

    2009-01-01

    Full Text Available The authors here describe manual small incision cataract surgery (MSICS by using topical anesthesia with intracameral 0.5% lignocaine, which eliminates the hazards of local anesthesia, cuts down cost and time taken for the administration of local anesthesia. Aims: To evaluate the patients′ and surgeons′ experience in MSICS using topical anesthesia with intracameral lignocaine in terms of pain, surgical complications, and outcome. Settings and Design: Prospective interventional case series. Materials and Methods: Ninety-six patients of senile cataract were operated by MSICS under topical anesthesia with intracameral lignocaine using "fish hook technique." The patients and the single operating surgeon were given a questionnaire to evaluate their experience in terms of pain, surgical experience, and complications. Statistical Analysis Used: Statistical analysis software "Analyseit." Results: There were 96 patients enrolled in the study. The mean pain score was 0.7 (SD ± 0.97, range 0-5, median 0.0, and mode 0.0. Fifty-one patients (53% had pain score of zero, that is, no pain. Ninety-one patients (~95% had a score of less than 3, that is, mild pain to none. All the surgeries were complication-free except one and the surgeon′s experience was favorable in terms of patient′s cooperation, anterior chamber stability, difficulty, and complications. The ocular movements were not affected, and hence, the eye patch could be removed immediately following the surgery. Conclusions: MSICS can be performed under topical anesthesia with intracameral lignocaine, which makes the surgery patient friendly, without compromising the outcome.

  2. Topiramate modulates trigeminal pain processing in thalamo-cortical networks in humans after single dose administration

    OpenAIRE

    Hebestreit, Julia M.; May, Arne

    2017-01-01

    Migraine is the sixth most common cause of disability in the world. Preventive migraine treatment is used to reduce frequency, severity and duration of attacks and therefore lightens the burden on the patients' quality of life and reduces disability. Topiramate is one of the preventive migraine treatments of proven efficacy. The mechanism of action underlying the preventive effect of topiramate in migraine remains largely unknown. Using functional magnetic resonance imaging (fMRI) we examined...

  3. An E-learning Module on Chronic Low Back Pain in Older Adults: Effect on Medical Resident Attitudes, Confidence, Knowledge, and Clinical Skills.

    Science.gov (United States)

    Jacobs, Zachary G; Elnicki, D Michael; Perera, Subashan; Weiner, Debra K

    2018-01-05

    To determine 1) the feasibility of implementing an e-learning module on chronic low back pain (CLBP) in an older adult into an existing internal medicine residency curriculum and 2) the impact of this module on resident attitudes, confidence, knowledge, and clinical skills relating to CLBP. Participants were assigned to complete either the online module (N = 73) or the Yale Office-based curriculum on CLBP (N = 70). Attitudes, confidence, and knowledge were evaluated pre- and postintervention via survey. A retrospective blinded chart review of resident clinic encounters was conducted, wherein diagnosis codes and physical exam documentation were rated as basic or advanced. There was no improvement in overall knowledge scores in either group (60% average on both metrics). There were tendencies for greater improvements in the intervention group compared with controls for confidence in managing fibromyalgia (2.4 to 2.9 vs 2.5 to 2.5, P = 0.06) and leg length discrepancy (1.8 to 2.5 vs 1.5 to 1.9, P = 0.05). Those exposed to the online module also showed an increase in the percentage of physical exam documentation rated as advanced following the intervention (13% to 32%, P = 0.006), whereas the control group showed no change (14% to 12%, P = 0.68). An online module on CLBP in the older adult was a feasible addition to an existing curriculum for internal medicine residents. The module positively and substantively impacted resident clinical behaviors, as evidenced by enhanced sophistication in physical exam documentation; it also was associated with improved confidence in certain aspects of chronic pain management. © 2018 American Academy of Pain Medicine. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  4. Advanced power cycler with intelligent monitoring strategy of IGBT module under test

    DEFF Research Database (Denmark)

    Choi, U. M.; Blaabjerg, F.; Iannuzzo, F.

    2017-01-01

    and diode, which for the wear-out condition monitoring are presented. This advanced power cycler allows to perform power cycling test cost-effectively under conditions close to real power converter applications. In addition, an intelligent monitoring strategy for the separation of package-related wear......Power cycling (PC) test is one of the important test methods to assess the reliability performance of power device modules related to packaging technology, in respect to temperature stress. In this paper, an advanced power cycler with a real-time VCE_ON and VF measurement circuit for the IGBT...

  5. Two-photon exchange interaction from the Dicke Hamiltonian under parametric modulation

    Science.gov (United States)

    Dodonov, A. V.

    2018-02-01

    We consider the nonstationary circuit QED architecture in which a single-mode cavity interacts with N >1 identical qubits, and some system parameters undergo a weak external perturbation. It is shown that in the dispersive regime one can engineer the two-photon exchange interaction by adjusting the frequency of harmonic modulation to (approximately) 2 | Δ-| , where Δ- is the average atom-field detuning. A closed analytic description is derived for the weak atom-field coupling regime, and the system dynamics under realistic conditions is studied numerically.

  6. Secret Underlying Unexplained Abdominal Pain, Neurological Symptoms and Intermittent Hypertension: Acute Intermittent Porphyria

    Directory of Open Access Journals (Sweden)

    Komac Andac

    2017-06-01

    Full Text Available A 21-year-old female patient with abdominal pain, vomiting and constipation was admitted to the hospital with the possible diagnosis of diabetic ketoacidosis. Due to increased abdominal pain and constipation the patient underwent a surgery with the diagnosis of ileus. However, no pathological findings were found in the abdominal organs apart from serous fluid in the abdominal cavity. The patient became hypertensive, tachycardic and had an episode of seizures postoperatively. Neurological manifestations with unexplained abdominal pain indicated a diagnosis of acute intermittent porphyria (AIP. Acute intermittent porphyria diagnosis is based on elevated urinary δ-aminolevulinic acid (ALA and porphobilinogen (PBG levels as well as hydroxymethylbilane synthase (HMBS IVS13-2 A>G heterozygous mutation. Familial Mediterranean Fever (FMF gene mutations were not confirmed. Porphyria should be considered in the differential diagnosis of patients with recurrent abdominal pain, neurological symptoms and lack of FMF gene polymorphism.

  7. A High Temperature Experimental Characterization Procedure for Oxide-Based Thermoelectric Generator Modules under Transient Conditions

    Directory of Open Access Journals (Sweden)

    Elena Anamaria Man

    2015-11-01

    Full Text Available The purpose of this study is to analyze the steady-state and transient behavior of the electrical and thermal parameters of thermoelectric generators (TEGs. The focus is on the required wait-time between measurements in order to reduce measurement errors which may appear until the system reaches steady-state. By knowing this waiting time, the total characterization time can also be reduced. The experimental characterization process is performed on a test rig known as TEGeta, which can be used to assess the output characteristics of TEG modules under different load values and temperature conditions. The setup offers the possibility to control the hot side temperature up to 1000 °C with a load variation range value between 0.22–8.13 Ω. A total of ten thermocouples are placed in the setup with the purpose of measuring the temperature in specific points between the heater and the heat sink. Based on the readings, the temperature on the hot and cold side of the modules can be extrapolated. This study provides quantitative data on the minimum waiting time of the temperatures in the surrounding system to reach equilibrium. Laboratory tests are performed on a calcium-manganese oxide module at temperatures between 400 and 800 °C to explore the high temperatures features of the setup.

  8. Self-Construal Priming Modulates Self-Evaluation under Social Threat

    Directory of Open Access Journals (Sweden)

    Tianyang Zhang

    2017-10-01

    Full Text Available Previous studies have shown that Westerners evaluate themselves in an especially flattering way when faced with a social-evaluative threat. The current study first investigated whether East Asians also have a similar pattern by recruiting Chinese participants and using social-evaluative threat manipulations in which participants perform self-evaluation tasks while adopting different social-evaluative feedbacks (Experiment 1. Then further examined whether the different response patterns can be modulated by different types of self-construal by using social-evaluative threat manipulations in conjunction with a self-construal priming task (Experiment 2. The results showed that, as opposed to Westerners' pattern, Chinese participants rated themselves as having significantly greater above-average effect only when faced with the nonthreatening feedback but not the social-evaluative threat. More importantly, we found that self-construal modulated the self-evaluation under social-evaluative threat: following independent self-construal priming, participants tended to show a greater above-average effect when faced with a social-evaluative threat. However, this pattern in conjunction with a social threat disappeared after participants received interdependent self-construal priming or neutral priming. These findings suggest that the effects of social-evaluative threat on self-evaluation are not culturally universal and is strongly modulated by self-construal priming.

  9. Modulation Methods for Three-level Neutral-Point-Clamped Inverter Achieving Stress Redistribution under Moderate Modulation Index

    DEFF Research Database (Denmark)

    Ma, Ke; Blaabjerg, Frede

    2016-01-01

    This letter investigates the loss and thermal behaviors of a three-level neutral-point-clamped (3L-NPC) inverter undergoing moderate modulation index, which is typically presented during minor voltage sags of the power grid or speed changes of the electric machines. A series of new space vector...... modulation methods is then proposed to relocate the thermal loading among the power devices. It is concluded that, with some of the proposed modulation methods, the device loading in the 3L-NPC inverter can be effectively modified and optimized, and the junction temperature of the most stressed devices can...

  10. Pain modulation effect of breathing-controlled electrical stimulation (BreEStim) is not likely to be mediated by deep and fast voluntary breathing

    Science.gov (United States)

    Hu, Huijing; Li, Shengai; Li, Sheng

    2015-01-01

    Voluntary breathing-controlled electrical stimulation (BreEStim), a novel non-invasive and non-pharmacological treatment protocol for neuropathic pain management, was reported to selectively reduce the affective component of pain possibly by increasing pain threshold. The underlying mechanisms involved in the analgesic effect of BreEStim were considered to result from combination of multiple internal pain coping mechanisms triggered during BreEStim. Findings from our recent studies have excluded possible roles of acupuncture and aversiveness and habituation of painful electrical stimulation in mediating the analgesia effect of BreEStim. To further investigate the possible role of voluntary breathing during BreEStim, the effectiveness of fast and deep voluntary breathing-only and BreEStim on experimentally induced pain was compared in healthy human subjects. Results showed no change in electrical pain threshold after Breathing-only, but a significant increase in electrical pain threshold after BreEStim. There was no statistically significant change in other thresholds after Breathing-only and BreEStim. The findings suggest that the analgesic effect of BreEStim is not likely attributed to fast and deep voluntary breathing. Possible mechanisms are discussed. PMID:26382644

  11. Effect of Ketofol on Pain and Complication after Caesarean Delivery under Spinal Anaesthesia: A Randomized Double-blind Clinical Trial.

    Science.gov (United States)

    Jaafarpour, Molouk; Vasigh, Aminolah; Khajavikhan, Javaher; Khani, Ali

    2017-03-01

    Pain is the key concern of women after caesarean delivery that may interfere with breastfeeding. The aim of this study was to assess effect of ketofol (ketamine/propofol combination) on pain and complication after caesarean delivery under spinal anaesthesia. In this randomized double-blind clinical trial, 92 parturient scheduled for elective caesarean delivery under spinal anaesthesia were included. The simple random sampling method was used to place subjects in four groups of ketamine (0.25 mg/kg), propofol (0.25 mg/kg), ketofol (25 mg ketamine plus 25 mg propofol) and placebo (saline). The drugs were administered intravenously immediately after clamping the umbilical cord. Visual Analog Scale (VAS) was used to determine the intensity of pain. Complications after surgery including shivering, nausea and vomiting as well as onset of breastfeeding were recorded. The mean score of pain, morphine consumption and time of breastfeeding in the ketofol group were significantly lower than other groups at various intervals (ppain and complication after caesarean delivery indicated that it can be considered as a safe and alternative drug in these patients.

  12. A Novel Application of Thermoelectric Modules in an HVAC System Under Cold Climate Operation

    Science.gov (United States)

    Okuma, Toru; Radermacher, Reinhard; Hwang, Yunho

    2012-06-01

    A vapor compression cycle (VCC) with integrated thermoelectric (TE) modules to boost the heating capacity of the system in an energy-efficient way, especially for cold climate operation, is suggested in this paper. While a baseline heat pump (HP) cycle absorbs heat from a source through an evaporator, the proposed system utilizes TE modules as an intermediate (or third) stage of an otherwise two-stage vapor compression system with a vapor injection compressor. This increases the overall system efficiency and augments the system capacity through the high coefficient of performance (COP) of the TE for small temperature lift conditions. To demonstrate the concept, a prototype refrigerant-to-solid (TE) heat exchanger, consisting of TE modules and microchannel flat tubes, was designed and fabricated so that the whole system could realize an additional 1 kW of heating capacity compared with the baseline system. The TE heat exchanger was integrated into a residential HP unit that uses R-410A as a refrigerant, and the system was tested in a laboratory under the severe condition of -17.8°C, in order to investigate the capacity improvement and the overall COP. Finally, an application of this technique in an automotive heating, ventilating, and air-conditioning system with HFC134a working fluid has been studied for the purpose of providing supplemental heating for electric vehicles and hybrid electric vehicles by establishing a detailed simulation model of a HP system with the TE heat exchanger. Both the laboratory test and the calculation study show that a VCC with integrated TE modules has both reasonable efficiency and increased heating capacity.

  13. Cyclic Sciatica and Back Pain Responds to Treatment of Underlying Endometriosis: Case Illustration.

    Science.gov (United States)

    Uppal, Jaya; Sobotka, Stanislaw; Jenkins, Arthur L

    2017-01-01

    Multiple causes outside the spine can mimic spinal back pain. Endometriosis is an important gynecologic disorder, which commonly affects the lower region of the female pelvis and less frequently the spine and soft tissues. The lumbosacral trunk is vulnerable to pressure from any abdominal mass originating from the uterus and the ovaries. Therefore symptoms of endometriosis include severe reoccurring pain in the pelvic area as well as lower back and abdominal pain. We report on a 39-year-old gymnast with cyclic sciatica and back pain, whose initial presentation initially led to a spinal fusion at L4/5 and L5/S1, but that procedure did not change her symptoms. Her diagnosis of endometriosis was not made until 2 years after her spinal fusion. Ultimately, once diagnosed with endometriosis of the retroperitoneal spinal and neural elements, her back and leg pain responded completely to hormonal therapy and then to a hysterectomy and a bilateral salpingo-oophorectomy. Because her true diagnosis of endometriosis was unknown and she had some degenerative changes in her spine, she underwent a spinal fusion that would probably not have been done if the diagnosis of endometriosis had been suggested. It is critical for any clinician who deals with back pain to at least consider the diagnosis of endometriosis in female patients who have a history of pelvic pain. The diagnosis of endometriosis should be considered in candidate patients by asking whether there is a significant hormonal cyclic nature to the symptoms, to prevent such unnecessary surgical adventures. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Heat transfer and convective structure of evaporating films under pressure-modulated conditions

    Science.gov (United States)

    Gonzalez-Pons, Juan Carlos; Hermanson, James; Allen, Jeffrey

    2014-11-01

    The interfacial stability, convective structure, and evaporation rate of upward-facing, thin liquid films were studied experimentally. Dichloromethane films approximately 2 mm thick were subjected to impulsive, time-varying superheating. The films resided on a temperature controlled, copper surface in a closed, initially degassed test chamber. Superheating was achieved by modulating the pressure of the saturated pure vapor in the test chamber. The dynamic film thickness was measured at multiple points using ultrasound, and the convective structure information was visualized by schlieren imaging. Two distinct raises in heat transfer rate under unsteady conditions were observed. The first transition appears to be associated with conduction within the film only; the second, to a change in the pattern of convection within the film. Different pressure-modulation cycles were studied to capture one or both of the observed rises in heat transfer. The total film thickness change over multiple cycles, as indicated by ultrasound, allowed determination of the total heat rejected into the evaporating films. Results suggest that there are cycle combinations that lead to an elevation in the average rate of heat transfer compared to films undergoing quasi-steady evaporation. This work was sponsored by the National Aeronautics and Space Administration under Cooperative Agreement NNX09AL02G.

  15. Modulating conscious movement intention by noninvasive brain stimulation and the underlying neural mechanisms.

    Science.gov (United States)

    Douglas, Zachary H; Maniscalco, Brian; Hallett, Mark; Wassermann, Eric M; He, Biyu J

    2015-05-06

    Conscious intention is a fundamental aspect of the human experience. Despite long-standing interest in the basis and implications of intention, its underlying neurobiological mechanisms remain poorly understood. Using high-definition transcranial DC stimulation (tDCS), we observed that enhancing spontaneous neuronal excitability in both the angular gyrus and the primary motor cortex caused the reported time of conscious movement intention to be ∼60-70 ms earlier. Slow brain waves recorded ∼2-3 s before movement onset, as well as hundreds of milliseconds after movement onset, independently correlated with the modulation of conscious intention by brain stimulation. These brain activities together accounted for 81% of interindividual variability in the modulation of movement intention by brain stimulation. A computational model using coupled leaky integrator units with biophysically plausible assumptions about the effect of tDCS captured the effects of stimulation on both neural activity and behavior. These results reveal a temporally extended brain process underlying conscious movement intention that spans seconds around movement commencement. Copyright © 2015 Douglas et al.

  16. Gene-to-gene interactions regulate endogenous pain modulation in fibromyalgia patients and healthy controls—antagonistic effects between opioid and serotonin-related genes

    Science.gov (United States)

    Tour, Jeanette; Löfgren, Monika; Mannerkorpi, Kaisa; Gerdle, Björn; Larsson, Anette; Palstam, Annie; Bileviciute-Ljungar, Indre; Bjersing, Jan; Martin, Ingvar; Ernberg, Malin; Schalling, Martin; Kosek, Eva

    2017-01-01

    Abstract Chronic pain is associated with dysfunctional endogenous pain modulation, involving both central opioid and serotonergic (5-HT) signaling. Fibromyalgia (FM) is a chronic pain syndrome, characterized by widespread musculoskeletal pain and reduced exercise-induced hypoalgesia (EIH). In this study, we assessed the effects of 3 functional genetic polymorphisms on EIH in 130 patients with FM and 132 healthy controls. Subjects were genotyped regarding the mu-opioid receptor (OPRM1) gene (rs1799971), the serotonin transporter (5-HTT) gene (5-HTTLPR/rs25531), and the serotonin-1a receptor (5-HT1a) gene (rs6296). The patients with FM had increased pain sensitivity and reduced EIH compared with healthy controls. None of the polymorphisms had an effect on EIH on their own. We found significant gene-to-gene interactions between OPRM1 x 5-HTT and OPRM1 x 5-HT1a regarding activation of EIH, with no statistically significant difference between groups. Better EIH was found in individuals with genetically inferred strong endogenous opioid signaling (OPRM1 G) in combination with weak 5-HT tone (5-HTT low/5-HT1a G), compared with strong 5-HT tone (5-HTT high/5-HT1a CC). Based on the proposed mechanisms of these genetic variants, the findings indicate antagonistic interactions between opioid and serotonergic mechanisms during EIH. Moreover, despite different baseline pain level, similar results were detected in FM and controls, not supporting an altered interaction between opioid and 5-HT mechanisms as the basis for dysfunction of EIH in patients with FM. In summary, our results suggest that, by genetic association, the mu-opioid receptor interacts with 2 major serotonergic structures involved in 5-HT reuptake and release, to modulate EIH. PMID:28282362

  17. Gene-to-gene interactions regulate endogenous pain modulation in fibromyalgia patients and healthy controls-antagonistic effects between opioid and serotonin-related genes.

    Science.gov (United States)

    Tour, Jeanette; Löfgren, Monika; Mannerkorpi, Kaisa; Gerdle, Björn; Larsson, Anette; Palstam, Annie; Bileviciute-Ljungar, Indre; Bjersing, Jan; Martin, Ingvar; Ernberg, Malin; Schalling, Martin; Kosek, Eva

    2017-07-01

    Chronic pain is associated with dysfunctional endogenous pain modulation, involving both central opioid and serotonergic (5-HT) signaling. Fibromyalgia (FM) is a chronic pain syndrome, characterized by widespread musculoskeletal pain and reduced exercise-induced hypoalgesia (EIH). In this study, we assessed the effects of 3 functional genetic polymorphisms on EIH in 130 patients with FM and 132 healthy controls. Subjects were genotyped regarding the mu-opioid receptor (OPRM1) gene (rs1799971), the serotonin transporter (5-HTT) gene (5-HTTLPR/rs25531), and the serotonin-1a receptor (5-HT1a) gene (rs6296). The patients with FM had increased pain sensitivity and reduced EIH compared with healthy controls. None of the polymorphisms had an effect on EIH on their own. We found significant gene-to-gene interactions between OPRM1 x 5-HTT and OPRM1 x 5-HT1a regarding activation of EIH, with no statistically significant difference between groups. Better EIH was found in individuals with genetically inferred strong endogenous opioid signaling (OPRM1 G) in combination with weak 5-HT tone (5-HTT low/5-HT1a G), compared with strong 5-HT tone (5-HTT high/5-HT1a CC). Based on the proposed mechanisms of these genetic variants, the findings indicate antagonistic interactions between opioid and serotonergic mechanisms during EIH. Moreover, despite different baseline pain level, similar results were detected in FM and controls, not supporting an altered interaction between opioid and 5-HT mechanisms as the basis for dysfunction of EIH in patients with FM. In summary, our results suggest that, by genetic association, the mu-opioid receptor interacts with 2 major serotonergic structures involved in 5-HT reuptake and release, to modulate EIH.

  18. Mechanisms Underlying the Analgesic Effect of Moxibustion on Visceral Pain in Irritable Bowel Syndrome: A Review

    Directory of Open Access Journals (Sweden)

    Renjia Huang

    2014-01-01

    Full Text Available Irritable bowel syndrome (IBS is a functional bowel disorder that causes recurrent abdominal (visceral pain. Epidemiological data show that the incidence rate of IBS is as high as 25%. Most of the medications may lead to tolerance, addiction and toxic side effects. Moxibustion is an important component of traditional Chinese medicine and has been used to treat IBS-like abdominal pain for several thousand years in China. As a mild treatment, moxibustion has been widely applied in clinical treatment of visceral pain in IBS. In recent years, it has played an irreplaceable role in alternative medicine. Extensive clinical studies have demonstrated that moxibustion for treatment of visceral pain is simple, convenient, and inexpensive, and it is being accepted by an increasing number of patients. There have not been many studies investigating the analgesic mechanisms of moxibustion. Studies exploring the analgesic mechanisms have mainly focused on visceral hypersensitivity, brain-gut axis neuroendocrine system, and immune system. This paper reviews the latest developments in moxibustion use for treatment of visceral pain in IBS from these perspectives. It also evaluates potential problems in relevant studies on the mechanisms of moxibustion therapy to promote the application of moxibustion in the treatment of IBS.

  19. Distinct effects of reminding mortality and physical pain on the default-mode activity and activity underlying self-reflection.

    Science.gov (United States)

    Shi, Zhenhao; Han, Shihui

    2018-06-01

    Behavioral research suggests that reminding both mortality and negative affect influences self-related thoughts. Using functional magnetic resonance imaging (MRI), we tested the hypothesis that reminders of mortality and physical pain decrease brain activity underlying self-related thoughts. Three groups of adults underwent priming procedures during which they answered questions pertaining to mortality, physical pain, or leisure time, respectively. Before and after priming, participants performed personality trait judgments on oneself or a celebrity, identified the font of words, or passively viewed a fixation. The default-mode activity and neural activity underlying self-reflection were identified by contrasting viewing a fixation vs. font judgment and trait judgments on oneself vs. a celebrity, respectively. The analyses of the pre-priming functional MRI (fMRI) data identified the default-mode activity in the posterior cingulate cortex (PCC), ventral medial prefrontal cortex (MPFC), and parahippocampal gyrus, and the activity underlying instructed self-reflection in both the ventral and dorsal regions of the MPFC. The analyses of the post-priming fMRI data revealed that, relative to leisure time priming, reminding mortality significantly reduced the default-mode PCC activity, and reminding physical pain significantly decreased the dorsal MPFC activity during instructed self-reflection. Our findings suggest distinct neural underpinnings of the effect of reminding morality and aversive emotion on default-mode and instructed self-reflection.

  20. Molecular mechanisms underlying the enhanced analgesic effect of oxycodone compared to morphine in chemotherapy-induced neuropathic pain.

    Directory of Open Access Journals (Sweden)

    Karine Thibault

    Full Text Available Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone.

  1. Molecular mechanisms underlying the enhanced analgesic effect of oxycodone compared to morphine in chemotherapy-induced neuropathic pain.

    Science.gov (United States)

    Thibault, Karine; Calvino, Bernard; Rivals, Isabelle; Marchand, Fabien; Dubacq, Sophie; McMahon, Stephen B; Pezet, Sophie

    2014-01-01

    Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute) anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone.

  2. Facilitated Pronociceptive Pain Mechanisms in Radiating Back Pain Compared With Localized Back Pain

    DEFF Research Database (Denmark)

    Vaegter, Henrik Bjarke; Palsson, Thorvaldur Skuli; Graven-Nielsen, Thomas

    2017-01-01

    pressure pain threshold (cPPT), tolerance (cPTT), temporal summation of pain (TSP: increase in pain scores to ten repeated stimulations at cPTT intensity), and conditioning pain modulation (CPM: increase in cPPT during cuff pain conditioning on the contralateral leg). Heat detection (HDT) and heat pain...

  3. Melatonin Modulates Neuronal Cell Death Induced by Endoplasmic Reticulum Stress under Insulin Resistance Condition.

    Science.gov (United States)

    Song, Juhyun; Kim, Oh Yoen

    2017-06-10

    Insulin resistance (IR) is an important stress factor in the central nervous system, thereby aggravating neuropathogenesis and triggering cognitive decline. Melatonin, which is an antioxidant phytochemical and synthesized by the pineal gland, has multiple functions in cellular responses such as apoptosis and survival against stress. This study investigated whether melatonin modulates the signaling of neuronal cell death induced by endoplasmic reticulum (ER) stress under IR condition using SH-SY5Y neuroblastoma cells. Apoptosis cell death signaling markers (cleaved Poly [ADP-ribose] polymerase 1 (PARP), p53, and Bax) and ER stress markers (phosphorylated eIF2α (p-eIF2α), ATF4, CHOP, p-IRE1 , and spliced XBP1 (sXBP1)) were measured using reverse transcription-PCR, quantitative PCR, and western blottings. Immunofluorescence staining was also performed for p-ASK1 and p-IRE1 . The mRNA or protein expressions of cell death signaling markers and ER stress markers were increased under IR condition, but significantly attenuated by melatonin treatment. Insulin-induced activation of ASK1 ( p-ASK1 ) was also dose dependently attenuated by melatonin treatment. The regulatory effect of melatonin on neuronal cells under IR condition was associated with ASK1 signaling. In conclusion, the result suggested that melatonin may alleviate ER stress under IR condition, thereby regulating neuronal cell death signaling.

  4. Melatonin Modulates Neuronal Cell Death Induced by Endoplasmic Reticulum Stress under Insulin Resistance Condition

    Directory of Open Access Journals (Sweden)

    Juhyun Song

    2017-06-01

    Full Text Available Insulin resistance (IR is an important stress factor in the central nervous system, thereby aggravating neuropathogenesis and triggering cognitive decline. Melatonin, which is an antioxidant phytochemical and synthesized by the pineal gland, has multiple functions in cellular responses such as apoptosis and survival against stress. This study investigated whether melatonin modulates the signaling of neuronal cell death induced by endoplasmic reticulum (ER stress under IR condition using SH-SY5Y neuroblastoma cells. Apoptosis cell death signaling markers (cleaved Poly [ADP-ribose] polymerase 1 (PARP, p53, and Bax and ER stress markers (phosphorylated eIF2α (p-eIF2α, ATF4, CHOP, p-IRE1, and spliced XBP1 (sXBP1 were measured using reverse transcription-PCR, quantitative PCR, and western blottings. Immunofluorescence staining was also performed for p-ASK1 and p-IRE1. The mRNA or protein expressions of cell death signaling markers and ER stress markers were increased under IR condition, but significantly attenuated by melatonin treatment. Insulin-induced activation of ASK1 (p-ASK1 was also dose dependently attenuated by melatonin treatment. The regulatory effect of melatonin on neuronal cells under IR condition was associated with ASK1 signaling. In conclusion, the result suggested that melatonin may alleviate ER stress under IR condition, thereby regulating neuronal cell death signaling.

  5. 40-Gb/s directly-modulated photonic crystal lasers under optical injection-locking.

    Science.gov (United States)

    Chen, Chin-Hui; Takeda, Koji; Shinya, Akihiko; Nozaki, Kengo; Sato, Tomonari; Kawaguchi, Yoshihiro; Notomi, Masaya; Matsuo, Shinji

    2011-08-29

    CMOS integrated circuits (IC) usually requires high data bandwidth for off-chip input/output (I/O) data transport with sufficiently low power consumption in order to overcome pin-count limitation. In order to meet future requirements of photonic network interconnect, we propose an optical output device based on an optical injection-locked photonic crystal (PhC) laser to realize low-power and high-speed off-chip interconnects. This device enables ultralow-power operation and is suitable for highly integrated photonic circuits because of its strong light-matter interaction in the PhC nanocavity and ultra-compact size. High-speed operation is achieved by using the optical injection-locking (OIL) technique, which has been shown as an effective means to enhance modulation bandwidth beyond the relaxation resonance frequency limit. In this paper, we report experimental results of the OIL-PhC laser under various injection conditions and also demonstrate 40-Gb/s large-signal direct modulation with an ultralow energy consumption of 6.6 fJ/bit.

  6. Pain-related mood influences pain perception differently in fibromyalgia and multiple sclerosis

    Science.gov (United States)

    Borg, Céline; Padovan, Catherine; Thomas-Antérion, Catherine; Chanial, Céline; Sanchez, Anaïs; Godot, Marion; Peyron, Roland; De Parisot, Odile; Laurent, Bernard

    2014-01-01

    In patients, the perception of pain intensity may be influenced by the subjective representation of their disease. Although both multiple sclerosis (MS) and fibromyalgia (FM) possibly include chronic pain, they seem to elicit different disease representations because of the difference in their respective etiology, the former presenting evidence of underlying lesions as opposed to the latter. Thus, we investigated whether patients with FM differed from patients with MS with respect to their perception of “own” pain as well as others’ pain. In addition, the psychological concomitant factors associated with chronic pain were considered. Chronic pain patients with FM (n=13) or with MS (n=13) participated in this study. To assess specific pain-related features, they were contrasted with 12 other patients with MS but without chronic pain and 31 controls. A questionnaire describing imaginary painful situations showed that FM patients rated situations applied to themselves as less painful than did the controls. Additionally, pain intensity attributed to facial expressions was estimated as more intense in FM compared with the other groups of participants. There is good evidence that the mood and catastrophizing reactions expressed in FM differentially modulated the perception of pain according to whether it was their own pain or other’s pain. PMID:24489475

  7. The role of circulating sex hormones in menstrual cycle dependent modulation of pain-related brain activation

    Science.gov (United States)

    Veldhuijzen, Dieuwke S.; Keaser, Michael L.; Traub, Deborah S.; Zhuo, Jiachen; Gullapalli, Rao P.; Greenspan, Joel D.

    2013-01-01

    Sex differences in pain sensitivity have been consistently found but the basis for these differences is incompletely understood. The present study assessed how pain-related neural processing varies across the menstrual cycle in normally cycling, healthy females, and whether menstrual cycle effects are based on fluctuating sex hormone levels. Fifteen subjects participated in four test sessions during their menstrual, mid-follicular, ovulatory, and midluteal phases. Brain activity was measured while nonpainful and painful stimuli were applied with a pressure algometer. Serum hormone levels confirmed that scans were performed at appropriate cycle phases in 14 subjects. No significant cycle phase differences were found for pain intensity or unpleasantness ratings of stimuli applied during fMRI scans. However, lower pressure pain thresholds were found for follicular compared to other phases. Pain-specific brain activation was found in several regions traditionally associated with pain processing, including the medial thalamus, anterior and mid-insula, mid-cingulate, primary and secondary somatosensory cortices, cerebellum, and frontal regions. The inferior parietal lobule, occipital gyrus, cerebellum and several frontal regions demonstrated interaction effects between stimulus level and cycle phase, indicating differential processing of pain-related responses across menstrual cycle phases. Correlational analyses indicated that cycle-related changes in pain sensitivity measures and brain activation were only partly explained by varying sex hormone levels. These results show that pain-related cerebral activation varies significantly across the menstrual cycle, even when perceived pain intensity and unpleasantness remain constant. The involved brain regions suggest that cognitive pain or more general bodily awareness systems are most susceptible to menstrual cycle effects. PMID:23528204

  8. In vivo pharmacological interactions between a type II positive allosteric modulator of α7 nicotinic ACh receptors and nicotinic agonists in a murine tonic pain model.

    Science.gov (United States)

    Freitas, K; Negus, S S; Carroll, F I; Damaj, M I

    2013-06-01

    The α7 nicotinic ACh receptor subtype is abundantly expressed in the CNS and in the periphery. Recent evidence suggests that α7 nicotinic ACh receptor (nAChR) subtypes, which can be activated by an endogenous cholinergic tone comprising ACh and the α7 agonist choline, play an important role in chronic pain and inflammation. In this study, we evaluated whether type II α7 positive allosteric modulator PNU-120596 induces antinociception on its own and in combination with choline in the formalin pain model. We assessed the effects of PNU-120596 and choline and the nature of their interactions in the formalin test using an isobolographic analysis. In addition, we evaluated the interaction of PNU-120596 with PHA-54613, an exogenous selective α7 nAChR agonist, in the formalin test. Finally, we assessed the interaction between PNU-120596 and nicotine using acute thermal pain, locomotor activity, body temperature and convulsing activity tests in mice. We found that PNU-120596 dose-dependently attenuated nociceptive behaviour in the formalin test after systemic administration in mice. In addition, mixtures of PNU-120596 and choline synergistically reduced formalin-induced pain. PNU-120596 enhanced the effects of nicotine and α7 agonist PHA-543613 in the same test. In contrast, PNU-120596 failed to enhance nicotine-induced convulsions, hypomotility and antinociception in acute pain models. Surprisingly, it enhanced nicotine-induced hypothermia via activation of α7 nAChRs. Our results demonstrate that type II α7 positive allosteric modulators produce antinociceptive effects in the formalin test through a synergistic interaction with the endogenous α7 agonist choline. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  9. Electronic transport in armchair graphene nanoribbon under double magnetic barrier modulation

    Science.gov (United States)

    Wang, Haiyan; Wu, Chao; Xie, Fang; Zhang, Xiaojiao; Zhou, Guanghui

    2018-03-01

    We present a theoretical investigation of the transport properties and the magnetoresistance effect in armchair graphene nanoribbons (AGNRs) under modulation by two magnetic barriers. The energy levels are found to be degenerate for a metallic AGNR but are not degenerate for a semiconducting AGNR. However, the conductance characteristics show quantized plateaus in both the metallic and semiconducting cases. When the magnetization directions of the barriers change from parallel to antiparallel, the conductance plateau in the metallic AGNR shows a degenerate feature due to matching between the transport modes in different regions. As the barrier height increases, the conductance shows more oscillatory behavior with sharp peaks and troughs. Specifically, the initial position of nonzero conductance for the metallic AGNR system moves towards a higher energy regime, which indicates that an energy gap has been opened. In addition, the magnetoresistance ratio also shows plateau structures in certain specific energy regions. These results may be useful in the design of electron devices based on AGNR nanostructures.

  10. Extended Delivery Time Analysis for Secondary Packet Transmission With Adaptive Modulation Under Interweave Cognitive Implementation

    KAUST Repository

    Wang, Wen-Jing

    2017-05-02

    Cognitive radio communication can opportunistically access underutilized spectrum for emerging wireless applications. With interweave cognitive implementation, a secondary user (SU) transmits only if primary user does not occupy the channel and waits for transmission otherwise. Therefore, secondary packet transmission involves both transmission periods and waiting periods. The resulting extended delivery time (EDT) is critical to the throughput analysis of secondary system. In this paper, we study the EDT of secondary packet transmission with adaptive modulation under interweave implementation to facilitate the delay analysis of such cognitive radio system. In particular, we propose an analytical framework to derive the probability density functions of EDT considering random-length SU transmission and waiting periods. We also present selected numerical results to illustrate the mathematical formulations and to verify our analytical approach.

  11. Band-gap modulation of graphane-like SiC nanoribbons under uniaxial elastic strain

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Ben-Ling, E-mail: jsblgao@gmail.com [Department of Physics, Huaiyin Institute of Technology, Huaian 223003 (China); Department of Physics, Nanjing University, Nanjing 210093 (China); Xu, Qing-Qiang [Department of Physics, Xuzhou Normal University, Xuzhou 221009 (China); Ke, San-Huang, E-mail: shke@tongji.edu.cn [MOE Key Laboratory of Advanced Micro-Structured Materials, School of Physics Science and Engineering, Tongji University, 1239 Siping Road, Shanghai 200092 (China); Beijing Computational Science Research Center, 3 Heqing Road, Beijing 100084 (China); Xu, Ning [Department of Physics, Yancheng Institute of Technology, Yancheng 224051 (China); Hu, Guang; Wang, Yanzong; Liang, Feng; Tang, Yalu [Department of Physics, Huaiyin Institute of Technology, Huaian 223003 (China); Xiong, Shi-Jie [Department of Physics, Nanjing University, Nanjing 210093 (China)

    2014-01-24

    The band-gap modulation of zigzag and armchair graphane-like SiC nanoribbons (GSiCNs) under uniaxial elastic strain is investigated using the density functional theory. The results show that band gap of both structures all decreases when being compressed or tensed. In compression, both zigzag and armchair GSiCNs are semiconductors with a direct band gap. However, in tension, the armchair GSiCNs undergo a direct-to-indirect band-gap transition but the zigzag GSiCNs still have a direct band gap. These results are also proved by HSE06 method. This implies a potential application of the graphane-like SiC nanoribbons in the future pressure sensor and optical electronics nanodevices.

  12. Growth response modulation by putrescine in Indian mustard Brassica juncea L. under multiple stress.

    Science.gov (United States)

    Lakra, Nita; Tomar, Pushpa C; Mishra, S N

    2016-04-01

    Plants, in general, are put to various kinds of stress, biotic and abiotic, both natural and manmade. Infestation by insect pests and diseases, and extreme conditions such as salinity, temperature, etc., as well as heavy metal contamination affect their growth performance. Here, we studied the impact of salinity and heavy metal pollution on the growth performance of Indian Mustard Brassica juncea L. and its amelioration by the diamine, putrescine, a known media supplement. We evaluated the putrescine (Put) modulation potential on multiple stress effect in 7-day old Indian mustard. The germination, seedlings length and photosynthetic pigments decline under salinity and metal (Cd/Pb) stress condition, alone or in combination, were checked by putrescine. The stress induced increase in root-shoot ratio, RNA and total amino acids content, as well as Na⁺/K⁺ ratio in leaf tissues were also comparatively less. The increased endogenous Cd/Pb accumulation in plants exposed to either metal further elevated under salinity was also found decelerated. However, the multiple stressed seedlings showed increase in glutathione content, which was further elevated with putrescine application. The increase in protein contents in leaf under single or combined stresses in the presence of putrescine could be a qualitative change. The differential changes in parameters examined here resulted in improved growth (> 10%) suggests stress mitigation by the putrescine up to an extent.

  13. Kinetin modulates physio-hormonal attributes and isoflavone contents of Soybean grown under salinity stress.

    Science.gov (United States)

    Hamayun, Muhammad; Hussain, Anwar; Khan, Sumera Afzal; Irshad, Muhammad; Khan, Abdul Latif; Waqas, Muhammad; Shahzad, Raheem; Iqbal, Amjad; Ullah, Nazif; Rehman, Gauhar; Kim, Ho-Youn; Lee, In-Jung

    2015-01-01

    Crop productivity continues to decline due to a wide array of biotic and abiotic stresses. Salinity is one of the worst abiotic stresses, as it causes huge losses to crop yield each year. Kinetin (Kn) has been reported as plant growth regulator since long, but its role in improving plant growth and food quality under saline conditions through mediating phytohormonal cross-talk is poorly studied. Current study was designed to evaluate the impact of exogenously applied Kn on growth, isoflovones and endogenous phytohormones of soybean grown under NaCl induced salt stress. Soybean plants were grown in perlite (semi hydroponic), and under controlled green-house conditions. Elevated levels of exogenous Kn significantly mitigated the adverse effect of NaCl and rescued plant growth attributes, i.e., plant height, fresh and dry biomass of soybean plants grown in all treatments. Higher diadzen, glycitin, and genistin contents were observed in plants treated with elevated Kn in the presence or absence of NaCl induce salt stress. The gibberellins (GAs) biosynthesis pathway was up-regulated by Kn as the bioactive GA1 and GA4 contents were significantly higher in Kn treated plants, as compared to control, while GAs level reduced in NaCl treated plants. Contrary to GAs, the abscisic acid contents declined with Kn but promoted in NaCl stressed soybean plants. The endogenous jasmonic acid and salicylic acid contents of soybean enhanced with elevated Kn application, but they showed an antagonistic response under salt stress. Current study supports the active role of Kn to ameliorate the adverse effects of salt stress on the growth and food quality of soybean. The favorable role of Kn toward soybean growth under salt stress may be attributed to its potential to modulate cross-talk between the various phytohormones involved in soybean growth and its resistance to salinity stress.

  14. Power cycling test and failure analysis of molded Intelligent Power IGBT Module under different temperature swing durations

    DEFF Research Database (Denmark)

    Choi, Uimin; Blaabjerg, Frede; Jørgensen, Søren

    2016-01-01

    on the lifetime of 600 V, 30 A, 3-phase molded Intelligent PowerModules (IPM) and their failuremechanismsare investigated. The study is based on the accelerated power cycling test results of 36 samples under 6 different conditions and tests are performed under realistic electrical conditions by an advanced power...

  15. Modulation of leptin, insulin, and growth hormone in obese pony mares under chronic nutritional restriction and supplementation with ractopamine hydrochloride.

    Science.gov (United States)

    Buff, Preston R; Johnson, Philip J; Wiedmeyer, Charles E; Ganjam, Venkataseshu K; Messer Iv, Nat T; Keisler, Duane H

    2006-01-01

    Horses fed beyond their nutritional requirement and that are physically inactive will develop obesity, which is often accompanied by insulin resistance and heightened risk of laminitis. The use of pharmacologic agents in combination with nutritional restriction may promote weight loss in obese horses unable to exercise because of laminitic pain. This study shows that reducing feed intake of brome grass hay to 75% of ad libitum intake in obese pony mares reduces body weight without induced exercise. Additional supplementation of ractopamine hydrochloride for 6 weeks resulted in a tendency for increased weight loss. Subsequent modulation of obesity-associated hormones, leptin and insulin, as a result of caloric restriction was observed.

  16. Effect of Intravenous Infusion of Lidocaine on Pain Reduction after Cesarean Section under General Anesthesia

    Directory of Open Access Journals (Sweden)

    Anahita Hirmanpour

    2018-01-01

    Full Text Available Background: The present study was conducted to evaluate the effect of Lidocaine on pain reduction during and ileus and the need for opioids after caesarean section. Methods: For this randomized double-blind controlled clinical trial, 40 ASA I, II pregnant women who were candidates for caesarean section with general anesthesia, were randomly allocated into two groups of Lidocaine receivers and placebo using randomized block design; the Lidocaine group received 1.5 mg/kg of Lidocaine right before the surgery and then its infusion with a dose of 2 mg/kg.h until the end of the surgery and the placebo group received normal saline with the same volume and application. Patients’ pain intensity was measured using numerical rating scale (NRS, 0 (entering the recovery, 0.5, 1, 4, 12 and 24 hours after the surgery. Results: Lidocaine decreased the systolic and diastolic pressures of the patients only during the first minute after intubation, decreased the mean of arterial blood pressure at the 10th minute after intubation and 40th minute after surgery, and also decreased the mean of patients’ pain intensity, Diclofenac and Pethidine consumption, side effects (nausea and vomiting and reduced the time interval before the first time of tolerating oral liquids; but it had effect on infants’ Apgar score 1 and 5 minutes after delivery. Conclusions: Lidocaine was definitely effective on reducing the intensity of pain, opioid and non-steroidal anti-inflammatory drugs consumption and ileus after surgery with the least occurrence of side effects for mothers and infants.

  17. Representational momentum in dynamic facial expressions is modulated by the level of expressed pain: Amplitude and direction effects.

    Science.gov (United States)

    Prigent, Elise; Amorim, Michel-Ange; de Oliveira, Armando Mónica

    2018-01-01

    Humans have developed a specific capacity to rapidly perceive and anticipate other people's facial expressions so as to get an immediate impression of their emotional state of mind. We carried out two experiments to examine the perceptual and memory dynamics of facial expressions of pain. In the first experiment, we investigated how people estimate other people's levels of pain based on the perception of various dynamic facial expressions; these differ both in terms of the amount and intensity of activated action units. A second experiment used a representational momentum (RM) paradigm to study the emotional anticipation (memory bias) elicited by the same facial expressions of pain studied in Experiment 1. Our results highlighted the relationship between the level of perceived pain (in Experiment 1) and the direction and magnitude of memory bias (in Experiment 2): When perceived pain increases, the memory bias tends to be reduced (if positive) and ultimately becomes negative. Dynamic facial expressions of pain may reenact an "immediate perceptual history" in the perceiver before leading to an emotional anticipation of the agent's upcoming state. Thus, a subtle facial expression of pain (i.e., a low contraction around the eyes) that leads to a significant positive anticipation can be considered an adaptive process-one through which we can swiftly and involuntarily detect other people's pain.

  18. Analysis of output characteristics of PV modules under natural sunlight; Shizen taiyokoka ni okeru taiyo denchi module shutsuryoku tokusei no kaiseki

    Energy Technology Data Exchange (ETDEWEB)

    Murai, Y.; Igari, S. [Japan Quality Assurance of Organization, Tokyo (Japan)

    1997-11-25

    The paper measured current/voltage characteristics of various PV modules under natural light and analyzed various characteristics such as generated output and module power generation efficiency. In the experiment, installing various PV modules at the solar techno center located at north latitude 34.7deg and east longitude 137.6deg, measurement was made by I-V curve tracer, pyranometer, and thermocouple buried on the module back. As a result, the following were confirmed: As to the monthly mean power generation efficiency, the crystalline system is lowest in summer and highest in winter, and the amorphous system highest in summer and lowest in winter. Concerning the power generation efficiency and illuminance, the gap of power generation efficiency between at high illuminance and at low illuminance is large in the crystalline system and small in amorphous system. Relating to the azimuth angle of module installation and the generated output, the installation inclined 15deg angle west in summer and 15deg angle east in fall/winter generates more power in the crystalline system. On the contrary, the installation on the south face generates more power in the amorphous system. 4 refs., 8 figs., 3 tabs.

  19. Prospective estimation of organ dose in CT under tube current modulation

    International Nuclear Information System (INIS)

    Tian, Xiaoyu; Li, Xiang; Segars, W. Paul; Frush, Donald P.; Samei, Ehsan

    2015-01-01

    Purpose: Computed tomography (CT) has been widely used worldwide as a tool for medical diagnosis and imaging. However, despite its significant clinical benefits, CT radiation dose at the population level has become a subject of public attention and concern. In this light, optimizing radiation dose has become a core responsibility for the CT community. As a fundamental step to manage and optimize dose, it may be beneficial to have accurate and prospective knowledge about the radiation dose for an individual patient. In this study, the authors developed a framework to prospectively estimate organ dose for chest and abdominopelvic CT exams under tube current modulation (TCM). Methods: The organ dose is mainly dependent on two key factors: patient anatomy and irradiation field. A prediction process was developed to accurately model both factors. To model the anatomical diversity and complexity in the patient population, the authors used a previously developed library of computational phantoms with broad distributions of sizes, ages, and genders. A selected clinical patient, represented by a computational phantom in the study, was optimally matched with another computational phantom in the library to obtain a representation of the patient’s anatomy. To model the irradiation field, a previously validated Monte Carlo program was used to model CT scanner systems. The tube current profiles were modeled using a ray-tracing program as previously reported that theoretically emulated the variability of modulation profiles from major CT machine manufacturers Li et al., [Phys. Med. Biol. 59, 4525–4548 (2014)]. The prediction of organ dose was achieved using the following process: (1) CTDI vol -normalized-organ dose coefficients (h organ ) for fixed tube current were first estimated as the prediction basis for the computational phantoms; (2) each computation phantom, regarded as a clinical patient, was optimally matched with one computational phantom in the library; (3) to

  20. Continuous Transmission Frequency Modulation Detection under Variable Sonar-Target Speed Conditions

    Directory of Open Access Journals (Sweden)

    Jun Yang

    2013-03-01

    Full Text Available As a ranging sensor, a continuous transmission frequency modulation (CTFM sonar with its ability for range finding and range profile formation works effectively under stationary conditions. When a relative velocity exists between the target and the sonar, the echo signal is Doppler-shifted. This situation causes the output of the sensor to deviate from the actual target range, thus limiting its applications to stationary conditions only. This work presents an approach for correcting such a deviation. By analyzing the Doppler effect during the propagation process, the sensor output can be corrected by a Doppler factor. To obtain this factor, a conventional CTFM system is slightly modified by adding a single tone signal with a frequency that locates out-of-sweep range of the transmitted signal. The Doppler factor can be extracted from the echo. Both verification experiments and performance tests are carried out. Results indicate the validity of the proposed approach. Moreover, ranging precision under different processing setups is discussed. For adjacent multiple targets, the discrimination ability is influenced by displacement and velocity. A discrimination boundary is provided through an analysis.

  1. Salmonella Modulates Metabolism During Growth under Conditions that Induce Expression of Virulence Genes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young-Mo; Schmidt, Brian; Kidwai, Afshan S.; Jones, Marcus B.; Deatherage, Brooke L.; Brewer, Heather M.; Mitchell, Hugh D.; Palsson, Bernhard O.; McDermott, Jason E.; Heffron, Fred; Smith, Richard D.; Peterson, Scott N.; Ansong, Charles; Hyduke, Daniel R.; Metz, Thomas O.; Adkins, Joshua N.

    2013-04-05

    Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative pathogen that uses complex mechanisms to invade and proliferate within mammalian host cells. To investigate possible contributions of metabolic processes in S. Typhimurium grown under conditions known to induce expression of virulence genes, we used a metabolomics-driven systems biology approach coupled with genome scale modeling. First, we identified distinct metabolite profiles associated with bacteria grown in either rich or virulence-inducing media and report the most comprehensive coverage of the S. Typhimurium metabolome to date. Second, we applied an omics-informed genome scale modeling analysis of the functional consequences of adaptive alterations in S. Typhimurium metabolism during growth under our conditions. Excitingly, we observed possible sequestration of metabolites recently suggested to have immune modulating roles. Modeling efforts highlighted a decreased cellular capability to both produce and utilize intracellular amino acids during stationary phase culture in virulence conditions, despite significant abundance increases for these molecules as observed by our metabolomics measurements. Model-guided analysis suggested that alterations in metabolism prioritized other activities necessary for pathogenesis instead, such as lipopolysaccharide biosynthesis.

  2. Modulation of laser-evoked potentials and pain perception by transcutaneous electrical nerve stimulation (TENS): a placebo-controlled study in healthy volunteers.

    Science.gov (United States)

    Vassal, François; Créac'h, C; Convers, Ph; Laurent, B; Garcia-Larrea, L; Peyron, R

    2013-09-01

    To investigate the effects of transcutaneous electrical nerve stimulation (TENS) on brain nociceptive responses (laser-evoked potentials, LEPs) and pain perception. Twenty healthy subjects were included. Nociceptive CO(2)-laser pulses were sequentially delivered to the dorsum of both feet. The amplitude of LEPs and nociceptive thresholds were collected in three consecutive conditions: T1: "sham" TENS (2 Hz/low-intensity) positioned heterotopically, over the left thigh; T2: "active" TENS (120 Hz/low-intensity) applied homotopically, over the left common peroneal nerve; and T3: "sham" TENS (replication of condition T1). Compared with "sham" TENS, "active" TENS significantly decreased the LEPs amplitude. This effect was observed exclusively when "active" TENS was applied ipsilaterally to the painful stimulus. Nociceptive thresholds increased with sessions in both limbs, but the increase observed during the "active" condition of TENS (T2) exceeded significantly that observed during the condition T3 only on the foot ipsilateral to TENS. Compared with a credible placebo TENS, high-frequency TENS induced a significant attenuation of both the acute pain and LEPs induced by noxious stimuli applied on the same dermatome. This modulation of subjective and objective concomitants of pain processing reflects a real neurophysiological TENS-related effect on nociceptive transmission. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  3. Pain relief in a young woman with adhesive capsulitis after manual manipulation of the acromioclavicular joint for remaining symptoms after mobilisation under anaesthesia.

    Science.gov (United States)

    Lilje, Stina; Genberg, Madeleine; Aldudjaili, Hassan; Skillgate, Eva

    2014-11-09

    Adhesive capsulitis is a painful condition with a prevalence of 2-5%. There is a lack of evidence for its aetiology and for conventional treatment and cost effects. This study describes the treatment effects of manual manipulation of the acromioclavicular joint for adhesive capsulitis in a young woman for persisting pain after mobilisation of the glenohumeral joint under anaesthesia. Primary outcomes were pain and physical function, measured by a visual analogue scale and the SF36 health survey. Secondary outcomes were sleep pattern, medication and perceived recovery. The mobility after manipulation under anaesthesia: elevation 55° and no improvement in pain. After manual manipulation: unrestricted elevation and significant pain relief. The patient no longer suffered from sleeping disorders and ceased all medication. Considering the lack of knowledge in aetiology and treatment, specialised manual examination of the acromioclavicular joint should be considered early in patients diagnosed with adhesive capsulitis. 2014 BMJ Publishing Group Ltd.

  4. Progesterone analogues reduce plasma Epstein–Barr virus DNA load and improve pain control in recurrent/metastatic nasopharyngeal carcinoma patients under supportive care

    Directory of Open Access Journals (Sweden)

    Chia-Yen Hung

    2017-08-01

    Conclusion: Progesterone analogues improve quality of life in terms of performance status, pain control, and plasma EBV DNA load in patients with locally recurrent/metastatic NPC under palliative care.

  5. Common modulation of limbic network activation underlies musical emotions as they unfold.

    Science.gov (United States)

    Singer, Neomi; Jacoby, Nori; Lin, Tamar; Raz, Gal; Shpigelman, Lavi; Gilam, Gadi; Granot, Roni Y; Hendler, Talma

    2016-11-01

    Music is a powerful means for communicating emotions among individuals. Here we reveal that this continuous stream of affective information is commonly represented in the brains of different listeners and that particular musical attributes mediate this link. We examined participants' brain responses to two naturalistic musical pieces using functional Magnetic Resonance imaging (fMRI). Following scanning, as participants listened to the musical pieces for a second time, they continuously indicated their emotional experience on scales of valence and arousal. These continuous reports were used along with a detailed annotation of the musical features, to predict a novel index of Dynamic Common Activation (DCA) derived from ten large-scale data-driven functional networks. We found an association between the unfolding music-induced emotionality and the DCA modulation within a vast network of limbic regions. The limbic-DCA modulation further corresponded with continuous changes in two temporal musical features: beat-strength and tempo. Remarkably, this "collective limbic sensitivity" to temporal features was found to mediate the link between limbic-DCA and the reported emotionality. An additional association with the emotional experience was found in a left fronto-parietal network, but only among a sub-group of participants with a high level of musical experience (>5years). These findings may indicate two processing-levels underlying the unfolding of common music emotionality; (1) a widely shared core-affective process that is confined to a limbic network and mediated by temporal regularities in music and (2) an experience based process that is rooted in a left fronto-parietal network that may involve functioning of the 'mirror-neuron system'. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Neural Habituation to Painful Stimuli Is Modulated by Dopamine: Evidence from a Pharmacological fMRI Study

    Directory of Open Access Journals (Sweden)

    Eva M. Bauch

    2017-12-01

    Full Text Available In constantly changing environments, it is crucial to adaptively respond to threatening events. In particular, painful stimuli are not only processed in terms of their absolute intensity, but also with respect to their context. While contextual pain processing can simply entail the repeated processing of information (i.e., habituation, it can, in a more complex form, be expressed through predictions of magnitude before the delivery of nociceptive information (i.e., adaptive coding. Here, we investigated the brain regions involved in the adaptation to nociceptive electrical stimulation as well as their link to dopaminergic neurotransmission (placebo/haloperidol. The main finding is that haloperidol changed the habituation to the absolute pain intensity over time. More precisely, in the placebo condition, activity in left postcentral gyrus and midcingulate cortex increased linearly with pain intensity only in the beginning of the experiment and subsequently habituated. In contrast, when the dopaminergic system was blocked by haloperidol, a linear increase with pain intensity was present throughout the entire experiment. Finally, there were no adaptive coding effects in any brain regions. Together, our findings provide novel insights into the nature of pain processing by suggesting that dopaminergic neurotransmission plays a specific role for the habituation to painful stimuli over time.

  7. The chemokine Bv8/prokineticin 2 is up-regulated in inflammatory granulocytes and modulates inflammatory pain

    OpenAIRE

    Giannini, Elisa; Lattanzi, Roberta; Nicotra, Annalisa; Campese, Antonio F.; Grazioli, Paola; Screpanti, Isabella; Balboni, Gianfranco; Salvadori, Severo; Sacerdote, Paola; Negri, Lucia

    2009-01-01

    Neutrophil migration into injured tissues is invariably accompanied by pain. Bv8/prokineticin 2 (PK2), a chemokine characterized by a unique structural motif comprising five disulfide bonds, is highly expressed in inflamed tissues associated to infiltrating cells. Here, we demonstrate the fundamental role of granulocyte-derived PK2 (GrPK2) in initiating inflammatory pain and driving peripheral sensitization. In animal models of complete Freund's adjuvant-induced paw inflammation the developme...

  8. The role of nicotinic acetylcholine and opioid systems of the ventral orbital cortex in modulation of formalin-induced orofacial pain in rats.

    Science.gov (United States)

    Yousofizadeh, Shahnaz; Tamaddonfard, Esmaeal; Farshid, Amir Abbas

    2015-07-05

    Nicotinic acetylcholine and opioid receptors are involved in modulation of pain. In the present study, we investigated the effects of microinjection of nicotinic acetylcholine and opioid compounds into the ventral orbital cortex (VOC) on the formalin-induced orofacial pain in rats. For this purpose, two guide cannulas were placed into the left and right sides of the VOC of the brain. Orofacial pain was induced by subcutaneous injection of a diluted formalin solution (50μl, 1.5%) into the right vibrissa pad and face rubbing durations were recorded at 3-min blocks for 45min. Formalin produced a marked biphasic pain response (first phase: 0-3min and second phase: 15-33min). Epibatidine (a nicotinic receptor agonist) at doses of 0.05, 0.1 and 0.2μg/site, morphine (an opioid receptor agonist) at doses of 0.5, 1 and 2μg/site and their sub-analgesic doses (0.025μg/site epibatidine with 0.25μg/site morphine) combination treatment suppressed the second phase of pain. The antinociceptive effect induced by 0.2μg/site of epibatidine, but not morphine (2μg/site), was prevented by 2μg/site of mecamylamine (a nicotinic receptor antagonist). Naloxone (an opioid receptor antagonist) at a dose of 2μg/site prevented the antinociceptive effects induced by 2μg/site of morphine and 0.2μg/site of epibatidine. No above-mentioned chemical compounds affected locomotor activity. These results showed that at the VOC level, epibatidine and morphine produced antinociception. In addition, opioid receptor might be involved in epibatidine-induced antinociception, but the antinociception induced by morphine was not mediated through nicotinic acetylcholine receptor. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Homogenized modeling methodology for 18650 lithium-ion battery module under large deformation

    Science.gov (United States)

    Tang, Liang; Cheng, Pengle

    2017-01-01

    Effective lithium-ion battery module modeling has become a bottleneck for full-size electric vehicle crash safety numerical simulation. Modeling every single cell in detail would be costly. However, computational accuracy could be lost if the module is modeled by using a simple bulk material or rigid body. To solve this critical engineering problem, a general method to establish a computational homogenized model for the cylindrical battery module is proposed. A single battery cell model is developed and validated through radial compression and bending experiments. To analyze the homogenized mechanical properties of the module, a representative unit cell (RUC) is extracted with the periodic boundary condition applied on it. An elastic–plastic constitutive model is established to describe the computational homogenized model for the module. Two typical packing modes, i.e., cubic dense packing and hexagonal packing for the homogenized equivalent battery module (EBM) model, are targeted for validation compression tests, as well as the models with detailed single cell description. Further, the homogenized EBM model is confirmed to agree reasonably well with the detailed battery module (DBM) model for different packing modes with a length scale of up to 15 × 15 cells and 12% deformation where the short circuit takes place. The suggested homogenized model for battery module makes way for battery module and pack safety evaluation for full-size electric vehicle crashworthiness analysis. PMID:28746390

  10. Homogenized modeling methodology for 18650 lithium-ion battery module under large deformation.

    Directory of Open Access Journals (Sweden)

    Liang Tang

    Full Text Available Effective lithium-ion battery module modeling has become a bottleneck for full-size electric vehicle crash safety numerical simulation. Modeling every single cell in detail would be costly. However, computational accuracy could be lost if the module is modeled by using a simple bulk material or rigid body. To solve this critical engineering problem, a general method to establish a computational homogenized model for the cylindrical battery module is proposed. A single battery cell model is developed and validated through radial compression and bending experiments. To analyze the homogenized mechanical properties of the module, a representative unit cell (RUC is extracted with the periodic boundary condition applied on it. An elastic-plastic constitutive model is established to describe the computational homogenized model for the module. Two typical packing modes, i.e., cubic dense packing and hexagonal packing for the homogenized equivalent battery module (EBM model, are targeted for validation compression tests, as well as the models with detailed single cell description. Further, the homogenized EBM model is confirmed to agree reasonably well with the detailed battery module (DBM model for different packing modes with a length scale of up to 15 × 15 cells and 12% deformation where the short circuit takes place. The suggested homogenized model for battery module makes way for battery module and pack safety evaluation for full-size electric vehicle crashworthiness analysis.

  11. Discovery of microRNA-target modules of African rice (Oryza glaberrima) under salinity stress.

    Science.gov (United States)

    Mondal, Tapan Kumar; Panda, Alok Kumar; Rawal, Hukam C; Sharma, Tilak Raj

    2018-01-12

    Oryza glaberrima is the second edible rice in the genus Oryza. It is grown in the African countries. miRNAs are regulatory molecules that are involved in every domains of gene expression including salinity stress response. Although several miRNAs have been reported from various species of Oryza, yet none of them are from this species. Salt treated (200 mM NaCl for 48 h) and control smallRNA libraries of RAM-100, a salt tolerant genotype, each with 2 replications generated 150 conserve and 348 novel miRNAs. We also used smallRNAseq data of NCBI of O. glaberrima to discover additional 246 known miRNAs. Totally, 29 known and 32 novel miRNAs were differentially regulated under salinity stress. Gene ontology and KEGG analysis indicated several targets were involved in vital biological pathways of salinity stress tolerance. Expression of selected miRNAs as indicated by Illumina data were found to be coherent with real time-PCR analysis. However, target gene expression was inversely correlated with their corresponding miRNAs. Finally based upon present results as well as existing knowledge of literature, we proposed the miRNA-target modules that were induced by salinity stress. Therefore, the present findings provide valuable information about miRNA-target networks in salinity adaption of O. glaberrima.

  12. Cross-layer combining of adaptive modulation and truncated ARQ under cognitive radio resource requirements

    KAUST Repository

    Yang, Yuli

    2012-11-01

    In addressing the issue of taking full advantage of the shared spectrum under imposed limitations in a cognitive radio (CR) network, we exploit a cross-layer design for the communications of secondary users (SUs), which combines adaptive modulation and coding (AMC) at the physical layer with truncated automatic repeat request (ARQ) protocol at the data link layer. To achieve high spectral efficiency (SE) while maintaining a target packet loss probability (PLP), switching among different transmission modes is performed to match the time-varying propagation conditions pertaining to the secondary link. Herein, by minimizing the SU\\'s packet error rate (PER) with each transmission mode subject to the spectrum-sharing constraints, we obtain the optimal power allocation at the secondary transmitter (ST) and then derive the probability density function (pdf) of the received SNR at the secondary receiver (SR). Based on these statistics, the SU\\'s packet loss rate and average SE are obtained in closed form, considering transmissions over block-fading channels with different distributions. Our results quantify the relation between the performance of a secondary link exploiting the cross-layer-designed adaptive transmission and the interference inflicted on the primary user (PU) in CR networks. © 1967-2012 IEEE.

  13. Local and regional heterogeneity underlying hippocampal modulation of cognition and mood

    Directory of Open Access Journals (Sweden)

    Lindsay eTannenholz

    2014-05-01

    Full Text Available While the hippocampus (HPC has been classically studied for its role in learning and memory, there is significant support for a role of the HPC in regulating emotional behavior. Emerging research suggests these functions may be segregated along the dorsoventral (DV axis of the HPC. In addition to this regional heterogeneity, within the HPC, the dentate gyrus (DG is one of two areas in the adult brain where stem cells continuously give rise to new neurons. This process can influence and be modulated by the emotional state of the animal, suggesting that adult neurogenesis within the DG may contribute to psychiatric disorders and cognitive abilities. Yet, the exact mechanism by which these newborn neurons influence behavior remains unknown. Here, we will examine the contribution of hippocampal neurogenesis to the output of the HPC, and suggest that the role of neurogenesis may vary along the DV axis. Next, we will review literature indicating that anatomical connectivity varies along the DV axis of the HPC, and that this underlies the functional segregation along this axis. This analysis will allow us to synthesize novel hypotheses for the differential contribution of the HPC to cognition and mood.

  14. Multiphoton-resonance-induced fluorescence of a strongly driven two-level system under frequency modulation

    Science.gov (United States)

    Yan, Yiying; Lü, Zhiguo; Luo, JunYan; Zheng, Hang

    2018-03-01

    We study the fluorescence spectrum of a strongly driven two-level system (TLS) with modulated transition frequency, which is a bichromatically driven TLS and has multiple resonance frequencies. We are aiming to provide a reliable description of the fluorescence in a regime that is difficult to tackle with perturbation theory and the rotating-wave approximation (RWA), and illustrate the spectral features of the fluorescence under off- and multiphoton-resonance conditions. To go beyond the RWA, we use a semianalytical counter-rotating-hybridized rotating-wave method that combines a unitary transformation and Floquet theory to calculate the two-mode Floquet states and quasienergies for the bichromatically driven TLS. We then solve the master equation accounting for the spontaneous decay in the bases of the two-mode Floquet states, and derive a physically transparent fluorescence spectrum. In comparison with the numerically exact spectrum from the generalized Floquet-Liouville approach, the present spectrum is found to be applicable in a wide range of the parameters where the RWA and the secular approximation may break down. We find that the counter-rotating (CR) terms of the transverse field omitted in the RWA have non-negligible contributions to the spectrum under certain conditions. Particularly, at the multiphoton resonance the width of which is comparable with the Bloch-Siegert shift, the RWA and non-RWA spectra markedly differ from each other because of the CR-induced shift. We also analyze the symmetry of the spectrum in terms of the transition matrix elements between the two-mode Floquet states. We show that the strict symmetry of the spectrum cannot be expected without the RWA but the almost symmetric spectrum can be obtained at the single-photon resonance that takes the Bloch-Siegert shift into account if the driving is moderately strong and at the multiphoton resonance with a sufficiently weak transverse field.

  15. Post-error action control is neurobehaviorally modulated under conditions of constant speeded response

    Directory of Open Access Journals (Sweden)

    Takahiro eSoshi

    2015-01-01

    Full Text Available Post-error slowing is an error recovery strategy that contributes to action control, and occurs after errors in order to prevent future behavioral flaws. Error recovery often malfunctions in clinical populations, but the relationship between behavioral traits and recovery from error is unclear in healthy populations. The present study investigated the relationship between impulsivity and error recovery by simulating a speeded response situation using a Go/No-go paradigm that forced the participants to constantly make accelerated responses prior to stimuli disappearance (stimulus duration: 250 ms. Neural correlates of post-error processing were examined using event-related potentials (ERPs. Impulsivity traits were measured with self-report questionnaires (BIS-11, BIS/BAS. Behavioral results demonstrated that the commission error for No-go trials was 15%, but post-error slowing did not take place immediately. Delayed post-error slowing was negatively correlated with error rates and impulsivity traits, showing that response slowing was associated with reduced error rates and changed with impulsivity. Response-locked error ERPs were clearly observed for the error trials. Contrary to previous studies, error ERPs were not significantly related to post-error slowing. Stimulus-locked N2 was negatively correlated with post-error slowing and positively correlated with impulsivity traits at the second post-error Go trial: larger N2 activity was associated with greater post-error slowing and less impulsivity. In summary, under constant speeded conditions, error monitoring was dissociated from post-error action control, and post-error slowing did not occur quickly. Furthermore, post-error slowing and its neural correlate (N2 were modulated by impulsivity traits. These findings suggest that there may be clinical and practical efficacy of maintaining cognitive control of actions during error recovery under common daily environments that frequently evoke

  16. Post-error action control is neurobehaviorally modulated under conditions of constant speeded response.

    Science.gov (United States)

    Soshi, Takahiro; Ando, Kumiko; Noda, Takamasa; Nakazawa, Kanako; Tsumura, Hideki; Okada, Takayuki

    2014-01-01

    Post-error slowing (PES) is an error recovery strategy that contributes to action control, and occurs after errors in order to prevent future behavioral flaws. Error recovery often malfunctions in clinical populations, but the relationship between behavioral traits and recovery from error is unclear in healthy populations. The present study investigated the relationship between impulsivity and error recovery by simulating a speeded response situation using a Go/No-go paradigm that forced the participants to constantly make accelerated responses prior to stimuli disappearance (stimulus duration: 250 ms). Neural correlates of post-error processing were examined using event-related potentials (ERPs). Impulsivity traits were measured with self-report questionnaires (BIS-11, BIS/BAS). Behavioral results demonstrated that the commission error for No-go trials was 15%, but PES did not take place immediately. Delayed PES was negatively correlated with error rates and impulsivity traits, showing that response slowing was associated with reduced error rates and changed with impulsivity. Response-locked error ERPs were clearly observed for the error trials. Contrary to previous studies, error ERPs were not significantly related to PES. Stimulus-locked N2 was negatively correlated with PES and positively correlated with impulsivity traits at the second post-error Go trial: larger N2 activity was associated with greater PES and less impulsivity. In summary, under constant speeded conditions, error monitoring was dissociated from post-error action control, and PES did not occur quickly. Furthermore, PES and its neural correlate (N2) were modulated by impulsivity traits. These findings suggest that there may be clinical and practical efficacy of maintaining cognitive control of actions during error recovery under common daily environments that frequently evoke impulsive behaviors.

  17. Comparative study of the energy potential of cyanide waters using two osmotic membrane modules under dead-end flow

    Science.gov (United States)

    García-Díaz, Y.; Quiñones-Bolaños, E.; Bustos-Blanco, C.; Vives-Pérez, L.; Bustillo-Lecompte, C.; Saba, M.

    2017-12-01

    The energy potential of the osmotic pressure gradient of cyanide waters is evaluated using two membrane modules, horizontal and vertical, operated under dead-end flow. The membrane was characterized using Scanning Electron Microscopy (SEM) with Energy Dispersive X-ray Spectroscopy (EDS). The membrane is mainly composed of carbon, oxygen, and sulphur. The properties of the membrane were unchanged and had no pore clogging after exposure to the cyanide waters. Potentials of 1.78×10-4 and 6.36×10-5Wm-2 were found for the horizontal and vertical modules, respectively, using the Van’t Hoff equation. Likewise, the permeability coefficient of the membrane was higher in the vertical module. Although the energy potential is low under the studied conditions the vertical configuration has a greater potential due to the action of gravity and the homogenous contact of the fluid with the membrane.

  18. Local and Generalized Endogenous Pain Modulation in Healthy Men: Effects of Exercise and Exercise-Induced Muscle Damage.

    Science.gov (United States)

    Black, Christopher D; Tynes, Brandon K; Gonglach, Alexander R; Waddell, Dwight E

    2016-12-01

    Isometric exercise has been shown to activate endogenous pain inhibitory pathways in healthy adults, but not in some clinical pain populations.  Exercise-induced muscle damage (EIMD) and the associated delayed-onset muscle soreness (DOMS) are a model for studying clinical pain; thus, our purpose was to examine the effects of isometric exercise on pressure pain threshold (PPT) in the presence and absence of DOMS.  Data were collected on 23 males (22.8 ± 2.5 yrs). PPT was assessed in the right (exercising) and left (resting) quadriceps prior to, every 30 seconds during, and 2 and 15 minutes following an isometric contraction of the right quadriceps at 25% of maximal voluntary contraction (MVC) held until fatigue. Unilateral eccentric exercise was performed to induce DOMS in the exercising leg and testing was repeated 48 hours later.  DOMS increased (P exercise in the exercising (P ≤ 0.002) and resting (P ≤ 0.002) quadriceps but did not differ between the control and EIMD conditions in either leg (P ≤ 0.61). PPT remained elevated 2 and 15 minutes postexercise (P exercised quadriceps in both conditions, but values returned to baseline at 2 (P = 0.91) and 15 minutes (P = 0.28) postisometric exercise in the resting quadriceps.  Unlike clinical pain, DOMS had no effect on the PPT response during exercise in either the exercising or resting quadriceps. The fact that exercise altered PPT in both quadriceps during exercise suggests a generalized pain inhibitory mechanism was activated. However, the restriction of postexercise effects to the exercised limb suggests localized inhibitory mechanism(s) were activated after exercise. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Individuals with chronic low back pain do not modulate the level of transversus abdominis muscle contraction across different postures.

    Science.gov (United States)

    Miura, Takuya; Yamanaka, Masanori; Ukishiro, Kengo; Tohyama, Harukazu; Saito, Hiroshi; Samukawa, Mina; Kobayashi, Takumi; Ino, Takumi; Takeda, Naoki

    2014-12-01

    The aim of this study was to evaluate the thickness of the transversus abdominis (TrA) muscle in three basic postures in subjects with and without chronic low back pain. Subjects were classified into a chronic low back pain group (n = 27) and a healthy control group (n = 23). The thickness of the TrA muscle was measured at rest and during the abdominal drawing-in manoeuvre (ADIM) in supine, sitting and standing postures using B-mode ultrasound imaging. Contraction ratio (TrA thickness during the ADIM/TrA thickness at rest) was calculated for each posture. At rest, the TrA thickness in the sitting and standing postures was significantly greater than in the supine posture (p low back pain group. TrA thickness was similar in the low back pain and control group in all three postures. During the ADIM, TrA thickness was significantly greater in the control group than in the chronic low back pain group in all three postures. The contraction ratio was also significantly higher in the control group than in the chronic low back pain group in all three postures. These results indicate that the automatic postural contraction of the TrA observed in the control subjects in the sitting and standing postures was not demonstrated in subjects with chronic low back pain. The present study revealed the one aspect of different response of the TrA muscle to changing posture between two groups. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Signaling pathway underlying the octopaminergic modulation of myogenic contraction in the cricket lateral oviduct.

    Science.gov (United States)

    Tamashiro, Hirotake; Yoshino, Masami

    2014-12-01

    Octopamine (OA), a biogenic monoamine, is a neurotransmitter and neuromodulator in invertebrates. Here, we report the effect of OA on the spontaneous rhythmic contractions (SRCs) of the lateral oviduct of the cricket Gryllus bimaculatus and the possible signaling pathway involved. Application of OA increased both the frequency and amplitude of SRCs in a dose-dependent manner. The effect of OA was inhibited by subsequent application of the OA receptor antagonist epinastine, indicating that the action of OA is mediated by OA receptor. To investigate the predominant signaling pathway underlying the action of OA, we first examined a possible involvement of the cAMP/cAMP-dependent protein kinase A (PKA) signaling pathway. Application of the membrane-permeable cAMP analog 8-Br-cAMP had little effect on SRCs and the effect of OA was not influenced by subsequent application of the PKA inhibitor H89, indicating that the cAMP/PKA signaling pathway is not the predominant pathway in the action of OA. Next, we examined a possible involvement of the second messenger inositol 1,4,5-trisphosphate in the action of OA. The effect of OA on SRCs was inhibited by subsequent application of the phosphoinositide-specific phospholipase C (PLC) inhibitor U73122, indicating that the PLC pathway is involved in the action of OA. The OA-induced increase in the frequency of SRCs was inhibited by pretreatment of the cell with the ryanodine receptor antagonist tetracaine but was not significantly affected by the IP3 receptor antagonist 2-aminoethoxydiphenyl borate (2-APB). On the other hand, the OA-induced increase in the amplitude of SRCs was inhibited by pretreatment of the cells with 2-APB but was not significantly affected by tetracaine. Taken together, these results suggest that the OA-induced excitatory effect on SRCs is mediated by the PLC signaling pathway: Ca2+ release from IP3 receptors may contribute to the modulation of the amplitude of SRCs, whereas Ca2+ release from ryanodine

  1. Central pain processing is altered in people with Achilles tendinopathy.

    Science.gov (United States)

    Tompra, Nefeli; van Dieën, Jaap H; Coppieters, Michel W

    2016-08-01

    Tendinopathy is often a chronic condition. The mechanisms behind persistent tendon pain are not yet fully understood. It is unknown whether, similar to other persistent pain states, central pain mechanisms contribute to ongoing tendon pain. We investigated the presence of altered central pain processing in Achilles tendinopathy by assessing the conditioned pain modulation (CPM) effect in people with and without Achilles tendinopathy. 20 people with Achilles tendinopathy and 23 healthy volunteers participated in this cross-sectional study. CPM was assessed by the cold pressor test. The pressure pain threshold (PPT) was recorded over the Achilles tendon before and during immersion of the participant's hand into cold water. The CPM effect was quantified as the absolute difference in PPT before and during the cold pressor test. An increase in PPT was observed in the Achilles tendinopathy and control group during the cold pressor test (ptendinopathy group (mean difference=36.4 kPa, SD=68.1 kPa; ptendinopathy compared to people without Achilles tendinopathy. A reduced conditioned pain modulation effect reflects altered central pain processing which is believed to contribute to the persistence of pain in other conditions. Altered central pain processing may also be an important factor in persistent tendon pain that has traditionally been regarded to be dominated by peripheral mechanisms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  2. Mechanisms underlying ectopic persistent tooth-pulp pain following pulpal inflammation.

    Science.gov (United States)

    Matsuura, Shingo; Shimizu, Kohei; Shinoda, Masamichi; Ohara, Kinuyo; Ogiso, Bunnai; Honda, Kuniya; Katagiri, Ayano; Sessle, Barry J; Urata, Kentaro; Iwata, Koichi

    2013-01-01

    In order to clarify the peripheral mechanisms of ectopic persistent pain in a tooth pulp following pulpal inflammation of an adjacent tooth, masseter muscle activity, phosphorylated extracellular signal-regulated protein kinase (pERK) and TRPV1 immunohistochemistries and satellite cell activation using glial fibrillary acidic protein (GFAP) immunohistochemistry in the trigeminal ganglion (TG) were studied in the rats with molar tooth-pulp inflammation. And, Fluorogold (FG) and DiI were also used in a neuronal tracing study to analyze if some TG neurons innervate more than one tooth pulp. Complete Freund's adjuvant (CFA) or saline was applied into the upper first molar tooth pulp (M1) in pentobarbital-anesthetized rats, and capsaicin was applied into the upper second molar tooth pulp (M2) on day 3 after the CFA or saline application. Mean EMG activity elicited in the masseter muscle by capsaicin application to M2 was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats. The mean number of pERK-immunoreactive (IR) TG cells was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats. Application of the satellite cell inhibitor fluorocitrate (FC) into TG caused a significant depression of capsaicin-induced masseter muscle activity and a significant reduction of satellite cell activation. The number of TRPV1-IR TG cells innervating M2 was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats, and that was decreased following FC injection into TG. Furthermore, 6% of TG neurons innervating M1 and/or M2 innervated both M1 and M2. These findings suggest that satellite cell activation following tooth pulp inflammation and innervation of multiple tooth pulps by single TG neurons may be involved in the enhancement of the activity of TG neurons innervating adjacent non-inflamed teeth that also show enhancement of TRPV1 expression in TG neurons, resulting in the ectopic persistent tooth-pulp pain

  3. Mechanisms underlying ectopic persistent tooth-pulp pain following pulpal inflammation.

    Directory of Open Access Journals (Sweden)

    Shingo Matsuura

    Full Text Available In order to clarify the peripheral mechanisms of ectopic persistent pain in a tooth pulp following pulpal inflammation of an adjacent tooth, masseter muscle activity, phosphorylated extracellular signal-regulated protein kinase (pERK and TRPV1 immunohistochemistries and satellite cell activation using glial fibrillary acidic protein (GFAP immunohistochemistry in the trigeminal ganglion (TG were studied in the rats with molar tooth-pulp inflammation. And, Fluorogold (FG and DiI were also used in a neuronal tracing study to analyze if some TG neurons innervate more than one tooth pulp. Complete Freund's adjuvant (CFA or saline was applied into the upper first molar tooth pulp (M1 in pentobarbital-anesthetized rats, and capsaicin was applied into the upper second molar tooth pulp (M2 on day 3 after the CFA or saline application. Mean EMG activity elicited in the masseter muscle by capsaicin application to M2 was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats. The mean number of pERK-immunoreactive (IR TG cells was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats. Application of the satellite cell inhibitor fluorocitrate (FC into TG caused a significant depression of capsaicin-induced masseter muscle activity and a significant reduction of satellite cell activation. The number of TRPV1-IR TG cells innervating M2 was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats, and that was decreased following FC injection into TG. Furthermore, 6% of TG neurons innervating M1 and/or M2 innervated both M1 and M2. These findings suggest that satellite cell activation following tooth pulp inflammation and innervation of multiple tooth pulps by single TG neurons may be involved in the enhancement of the activity of TG neurons innervating adjacent non-inflamed teeth that also show enhancement of TRPV1 expression in TG neurons, resulting in the ectopic persistent tooth

  4. PREEMPTIVE SINGLE-DOSE PREGABALIN IN MODULATION OF POSTOPERATIVE PAIN AND OPIOID REQUIREMENT AFTER LAPAROSCOPIC CHOLECYSTECTOMY- A RANDOMIZED CLINICAL STUDY

    Directory of Open Access Journals (Sweden)

    Rajib Hazarika

    2018-01-01

    Full Text Available BACKGROUND With the enormous advancement in the field of laparoscopic cholecystectomy, postoperative pain has substantially reduced as compared to open procedures. However, postoperative pain is still the most frequent complaint, which can hamper recovery, mandate inpatient admission and thereby increase the cost of such care. Preemptive analgesia attenuates sensitisation of pain before surgery so as to reduce postoperative hyperalgesia and allodynia. Pregabalin is a structural analog of γ-aminobutyric acid, which shows analgesic, anticonvulsant, and anxiolytic effects. The aim of the present study was to evaluate the effectiveness of preemptive oral pregabalin on postoperative pain and opioid consumption in patients undergoing laparoscopic cholecystectomy. MATERIALS AND METHODS Eighty adult patients of ASA I and II undergoing laparoscopic cholecystectomy were randomly divided into two groups to receive either pregabalin 150 mg capsule or a matching placebo (vitamin B complex capsule 1 hour before surgery. Anaesthesia technique was standardised in both the groups. Postoperative pain was assessed at 0, 1, 2, 3, 6, 9, 12, 18 and 24 hours period postoperatively by a 10 cm visual analogue scale, where 0, no pain; 10, worst imaginable pain. Subjects received Inj. Tramadol hydrochloride (1 mg/kg IV as a rescue analgesic whenever VAS score was ≥4. Occurrence of any side effects like nausea, vomiting, sedation, headache and dizziness was also noted. Statistical Analysis Used- Data analysis was done using PASW 18.0 software. Results were analysed by Mann-Whitney U-test, large sample difference in proportion test and Fisher’s Exact test. RESULTS Patients in the pregabalin group had significantly lower pain scores at all the time intervals in comparison to placebo group (p<0.05. Total postoperative tramadol consumption in the pregabalin group was statistically significantly lower than in the control group (p<0.05 and also time to first request for

  5. A High Temperature Experimental Characterization Procedure for Oxide-Based Thermoelectric Generator Modules under Transient Conditions

    DEFF Research Database (Denmark)

    Man, Elena Anamaria; Schaltz, Erik; Rosendahl, Lasse

    2015-01-01

    Characterization methods for thermoelectric generator (TEG) modules play an important role in studying their behavior and in enhancing the performance and simulation of TEG systems also. The purpose of this study is to analyze the behavior in transient and steady-state of the temperature applied...... is of experimental nature, it includes modules of different leg lengths and it is performed on a test rig known as TEGeta, which can be used to assess the output characteristics of TEG modules at different load values and temperature conditions. The setup offers the possibility to control the hot side temperature up...

  6. Periarticular Morphine-Induced Sphincter of Oddi Spasm Causing Severe Pain and Bradycardia in an Awake Patient Under Spinal Anesthesia: An Important Diagnostic Consideration.

    Science.gov (United States)

    Koumpan, Yuri; Engen, Dale; Tanzola, Robert; Saha, Tarit

    2016-10-01

    Sphincter of Oddi spasm from opioids has been documented, presenting as severe epigastric pain and potentially overlooked in a differential diagnosis. We present a case of sphincter of Oddi spasm from periarticular morphine in a patient under spinal anesthesia, causing severe distress and treated effectively with glucagon. It is important for anesthesiologists using opioids to consider it as a cause of perioperative pain and be familiar with treatment as it may be refractory by conventional use of opioids for pain relief. It is also important to consider the systemic effects of periarticular absorption, as evident by our case.

  7. The Biochemical Origin of Pain – Proposing a new law of Pain: The origin of all Pain is Inflammation and the Inflammatory Response PART 1 of 3 – A unifying law of pain

    Science.gov (United States)

    2009-01-01

    We are proposing a unifying theory or law of pain, which states: The origin of all pain is inflammation and the inflammatory response. The biochemical mediators of inflammation include cytokines, neuropeptides, growth factors and neurotransmitters. Irrespective of the type of pain whether it is acute or chronic pain, peripheral or central pain, nociceptive or neuropathic pain, the underlying origin is inflammation and the inflammatory response. Activation of pain receptors, transmission and modulation of pain signals, neuro plasticity and central sensitization are all one continuum of inflammation and the inflammatory response. Irrespective of the characteristic of the pain, whether it is sharp, dull, aching, burning, stabbing, numbing or tingling, all pain arise from inflammation and the inflammatory response. We are proposing a re-classification and treatment of pain syndromes based upon their inflammatory profile. Treatment of pain syndromes should be based on these principles: Determination of the inflammatory profile of the pain syndromeInhibition or suppression of production of the appropriate inflammatory mediators e.g. with inflammatory mediator blockers or surgical intervention where appropriateInhibition or suppression of neuronal afferent and efferent (motor) transmission e.g. with anti-seizure drugs or local anesthetic blocksModulation of neuronal transmission e.g. with opioid medication At the L.A. Pain Clinic, we have successfully treated a variety of pain syndromes by utilizing these principles. This theory of the biochemical origin of pain is compatible with, inclusive of, and unifies existing theories and knowledge of the mechanism of pain including the gate control theory, and theories of pre-emptive analgesia, windup and central sensitization. PMID:17240081

  8. Degradation analysis of thin film photovoltaic modules under outdoor long term exposure in Spanish continental climate conditions.

    OpenAIRE

    Silvestre Bergés, Santiago; Kichou, Sofiane; Guglielminotti, Letizia; Nofuentes Garrido, Gustavo; Alonso Abella, Miquel

    2016-01-01

    The present study analyses the degradation of thin film photovoltaic modules corresponding to four technologies: a-Si:H, a-Si:H/µc-Si:H, CIS and CdTe, under 5 years of outdoor long term exposure in Leganés, Spain. The period of outdoor exposure ranges from January 2011 to December 2015. The degradation rate and the stabilization period are analysed by using two different techniques. Moreover, the evolution of the fill factor and performance ratio is assessed. The CdTe module was found to hav...

  9. The comparison of intraincisional injection tramadol, pethidine and bupivacaine on postcesarean section pain relief under spinal anesthesia

    Directory of Open Access Journals (Sweden)

    Mitra Jabalameli

    2012-01-01

    Full Text Available Background: Bupivacaine, tramadol, and pethidine has local anesthetic effect. The aim of this study was to compare effect of subcutaneous (SC infiltration of tramadol, pethidine, and bupivacaine on postoperative pain relief after cesarean delivery. Materials and Methods: 120 patient, scheduled for elective cesarean section under spinal anesthesia, were randomly allocated to 1 of the 4 groups according to the drugs used for postoperative analgesia: Group P (Pethidine 50 mg ,Group T (Tramadol 40 mg, Group B (Bupivacaine 0.25% 0.7 mg/kg, and Group C (control 20CC normal saline injection in incision site of surgery. Pain intensity (VAS = visual analogous scale at rest and on coughing and opioid consumption were assessed on arrival in the recovery room, and then 15, 30, 60 minutes and 2, 6, 12, 24 hours after that. Results: VAS scores were significantly lower in groups T and P compared with groups B and C except for 24 hours (VAS rest and 6 hours (VAS on coughing postoperatively (P < 0.05. The number of patients requiring morphine were significantly different between the groups (105 doses vs. 87, 56, 46, doses for group C, B, T and P, respectively, P < 0.05 in all the times, except for 2 and 6 hours postoperatively. Conclusions: The administration of subcutaneous pethidine or tramadol after cesarean section improves analgesia and has a significant morphine-sparing effect compared with bupivacaine and control groups.

  10. Neurokinin-1 (NK-1 receptor and brain-derived neurotrophic factor (BDNF gene expression is differentially modulated in the rat spinal dorsal horn and hippocampus during inflammatory pain

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    McCarson Kenneth E

    2007-10-01

    Full Text Available Abstract Persistent pain produces complex alterations in sensory pathways of the central nervous system (CNS through activation of various nociceptive mechanisms. However, the effects of pain on higher brain centers, particularly the influence of the stressful component of pain on the limbic system, are poorly understood. Neurokinin-1 (NK-1 receptors and brain-derived neurotrophic factor (BDNF, known neuromediators of hyperalgesia and spinal central sensitization, have also been implicated in the plasticity and neurodegeneration occurring in the hippocampal formation during exposures to various stressors. Results of this study showed that injections of complete Freund's adjuvant (CFA into the hind paw increased NK-1 receptor and BDNF mRNA levels in the ipsilateral dorsal horn, supporting an important role for these nociceptive mediators in the amplification of ascending pain signaling. An opposite effect was observed in the hippocampus, where CFA down-regulated NK-1 receptor and BDNF gene expression, phenomena previously observed in immobilization models of stress and depression. Western blot analyses demonstrated that in the spinal cord, CFA also increased levels of phosphorylated cAMP response element-binding protein (CREB, while in the hippocampus the activation of this transcription factor was significantly reduced, further suggesting that tissue specific transcription of either NK-1 or BDNF genes may be partially regulated by common intracellular transduction mechanisms mediated through activation of CREB. These findings suggest that persistent nociception induces differential regional regulation of NK-1 receptor and BDNF gene expression and CREB activation in the CNS, potentially reflecting varied roles of these neuromodulators in the spinal cord during persistent sensory activation vs. modulation of the higher brain structures such as the hippocampus.

  11. Bone pain

    DEFF Research Database (Denmark)

    Frost, Charlotte Ørsted; Hansen, Rikke Rie; Heegaard, Anne-Marie

    2016-01-01

    Skeletal conditions are common causes of chronic pain and there is an unmet medical need for improved treatment options. Bone pain is currently managed with disease modifying agents and/or analgesics depending on the condition. Disease modifying agents affect the underlying pathophysiology...... of the disease and reduce as a secondary effect bone pain. Antiresorptive and anabolic agents, such as bisphosphonates and intermittent parathyroid hormone (1-34), respectively, have proven effective as pain relieving agents. Cathepsin K inhibitors and anti-sclerostin antibodies hold, due to their disease...... modifying effects, promise of a pain relieving effect. NSAIDs and opioids are widely employed in the treatment of bone pain. However, recent preclinical findings demonstrating a unique neuronal innervation of bone tissue and sprouting of sensory nerve fibers open for new treatment possibilities....

  12. [Clinical practice data regarding tapentadol prolonged release treatment for severe chronic pain - improvement of analgesia, functional competence and quality of life in particular under tapentadol monotherapy].

    Science.gov (United States)

    Lange, Thomas; Krings, Doris; Waldmann-Rex, Susanne

    2015-04-01

    To assess effectiveness and tolerability of tapentadol prolonged release (PR, Palexia® retard) for the treatment of severe chronic pain under routine clinical practice conditions in Germany. In this prospective non-interventional study, data regarding previous and concomitant analgesic treatment, tapentadol dosage, pain intensity, functionality, quality of life, and tolerability of tapentadol PR were collected over a 3-month observation period. A total of 5,002 patients were included in the effectiveness analysis; a subgroup analysis assessed effectiveness for all patients receiving tapentadol monotherapy (n = 1476). Nearly all patients of the total study population (95.9%) had already received analgesic long-term treatment (31.7% strong opioids) prior to the start of the study. Treatment with tapentadol PR (mean daily dose 216 ± 103 mg at end of observation) resulted in a reduction in pain intensity of 3.9 points from 7.2 ± 1.4 at baseline (95%CI -3.93; -3.83; p ≤ 0.001; NRS-11); clinically relevant pain relief ≥ 50% was documented for 65.1% of the patients. All 4 evaluated aspects regarding pain-related functionality, and quality of life of the patients also improved significantly. Compared to the total patient population, pain relief was greater in the subgroup receiving tapentadol monotherapy; baseline pain intensity was comparable between the groups. Pain-related functional impairment also declined to a slightly greater extent, and quality of life was rated more positively at end of observation. Analgesic treatment with tapentadol PR in routine clinical practice resulted in a marked reduction of severe chronic pain with significant improvements of functionality and quality of life. On the basis of these results and the favourable safety profile, tapentadol PR can thus be considered an alternative to classical opioids in the treatment of severe chronic pain.

  13. Deconstructing the sensation of pain: The influence of cognitive processes on pain perception.

    Science.gov (United States)

    Wiech, Katja

    2016-11-04

    Phenomena such as placebo analgesia or pain relief through distraction highlight the powerful influence cognitive processes and learning mechanisms have on the way we perceive pain. Although contemporary models of pain acknowledge that pain is not a direct readout of nociceptive input, the neuronal processes underlying cognitive modulation are not yet fully understood. Modern concepts of perception-which include computational modeling to quantify the influence of cognitive processes-suggest that perception is critically determined by expectations and their modification through learning. Research on pain has just begun to embrace this view. Insights into these processes promise to open up new avenues to pain prevention and treatment by harnessing the power of the mind. Copyright © 2016, American Association for the Advancement of Science.

  14. Identifying the Neural Correlates Underlying Social Pain: Implications for Developmental Processes

    Science.gov (United States)

    Eisenberger, Naomi I.

    2006-01-01

    Although the need for social connection is critical for early social development as well as for psychological well-being throughout the lifespan, relatively little is known about the neural processes involved in maintaining social connections. The following review summarizes what is known regarding the neural correlates underlying feeling of…

  15. 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 ) ...

  16. Motor Planning under Unpredictable Reward: Modulations of Movement Vigor and Primate Striatum Activity

    Directory of Open Access Journals (Sweden)

    Ioan eOpris

    2011-05-01

    Full Text Available Although reward probability is an important factor that shapes animal behavior, it is not well understood however, how the primate brain translates reward expectation into the vigor of movement (reaction time and speed. To address this question, we trained two monkeys in a reaction time task that required wrist movements in response to vibrotactile and visual stimuli, with a variable reward schedule. Correct performance was rewarded in 75 % of the trials. Monkeys were certain that they would be rewarded only in the trials immediately following withheld rewards. In these trials, the animals responded sooner and moved faster. Single-unit recordings from the dorsal striatum revealed that modulations in striatal neurons reflected such modulations of movement vigor. First, in the trials with certain rewards, striatal neurons modulated their firing rates earlier. Second, magnitudes of changes in neuronal firing rates depended on whether or not monkeys were certain about the reward. Third, these modulations depended on the sensory modality of the cue (visual vs. vibratory and/or movement direction (flexions vs. extensions. We conclude that dorsal striatum may be a part of the mechanism responsible for the modulation of movement vigor in response to changes of reward predictability.

  17. Topical Treatment with Xiaozheng Zhitong Paste (XZP Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL/RANK/OPG Signaling

    Directory of Open Access Journals (Sweden)

    Yanju Bao

    2015-01-01

    Full Text Available To explore the effects and mechanisms of Xiaozheng Zhitong Paste (XZP on bone cancer pain, Wistar rats were inoculated with vehicle or prostate cancer PC-3 into the tibia bone and treated topically with inert paste, XZP at 15.75, 31.5, or 63 g/kg twice per day for 21 days. Their bone structural damage, nociceptive behaviors, bone osteoclast and osteoblast activity, and the levels of OPG, RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were examined. In comparison with that in the placebo group, significantly reduced numbers of invaded cancer cells, decreased levels of bone damage and mechanical threshold and paw withdrawal latency, lower levels of serum TRACP5b, ICTP, PINP, and BAP, and less levels of bone osteoblast and osteoclast activity were detected in the XZP-treated rats (P<0.05. Moreover, significantly increased levels of bone OPG but significantly decreased levels of RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were detected in the XZP-treated rats (P<0.05 for all. Together, XZP treatment significantly mitigated the cancer-induced bone damage and bone osteoclast and osteoblast activity and alleviated prostate cancer-induced bone pain by modulating the RANKL/RANK/OPG pathway and bone cancer-related inflammation in rats.

  18. Mas-Related Gene (Mrg C Activation Attenuates Bone Cancer Pain via Modulating Gi and NR2B.

    Directory of Open Access Journals (Sweden)

    Yu'e Sun

    Full Text Available This study is to investigate the role of Mas-related gene (Mrg C in the pathogenesis and treatment of bone cancer pain (BCP.BCP mouse model was established by osteosarcoma cell inoculation. Pain-related behaviors were assessed with the spontaneous lifting behavior test and mechanical allodynia test. Expression levels of MrgC, Gi, and NR2B in the spinal cord were detected with Western blot analysis and immunohistochemistry.Pain-related behavior tests showed significantly increased spontaneous flinches (NSF and decreased paw withdrawal mechanical threshold (PWMT in mouse models of BCP. Western blot analysis showed that, compared with the control group and before modeling, all the expression levels of MrgC, Gi, and NR2B in the spinal cord of BCP mice were dramatically elevated, which were especially increased at day 7 after operation and thereafter, in a time-dependent manner. Moreover, the treatment of MrgC agonist BAM8-22 significantly up-regulated Gi and down-regulated NR2B expression levels, in the spinal cord of BCP mice, in a time-dependent manner. On the other hand, anti-MrgC significantly down-regulated Gi expression, while dramatically up-regulated NR2B expression, in the BCP mice. Similar results were obtained from the immunohistochemical detection. Importantly, BAM8-22 significantly attenuated the nociceptive behaviors in the BCP mice.Our results indicated the MrgC-mediated Gi and NR2B expression alterations in the BCP mice, which might contribute to the pain hypersensitivity. These findings may provide a novel strategy for the treatment of BCP in clinic.

  19. Fracture mechanics in new designed power module under thermo-mechanical loads

    Directory of Open Access Journals (Sweden)

    Durand Camille

    2014-06-01

    Full Text Available Thermo-mechanically induced failure is a major reliability issue in the microelectronic industry. On this account, a new type of Assembly Interconnected Technology used to connect MOSFETs in power modules has been developed. The reliability is increased by using a copper clip soldered on the top side of the chip, avoiding the use of aluminium wire bonds, often responsible for the failure of the device. Thus the new designed MOSFET package does not follow the same failure mechanisms as standard modules. Thermal and power cycling tests were performed on these new packages and resulting failures were analyzed. Thermo-mechanical simulations including cracks in the aluminium metallization and intermetallics (IMC were performed using Finite Element Analysis in order to better understand crack propagation and module behaviour.

  20. [The dimethyl sulfoxide under general anesthesia: An alternative after failure without anesthesia in the painful bladder syndrome/interstitial cystitis?

    Science.gov (United States)

    Gaullier, M; Tricard, T; Mouracade, P; Saussine, C

    2018-03-08

    The intravesical instillation of dimethyl sulfoxide (iDMSO), performed without anesthestic, is a therapeutic option for the painful bladder syndrome/interstial cystitis (PBS/IC). Some patients are against those iDMSO because of bad tolerance. Our study evaluates the tolerance and the outcome of the iDMSO under general anesthetic (GA) after the failure of the iDMSO without anesthetic. From May 2013 to April 2016, 11 patients with a PBS, 9 women (81.8 %), have been treated by iDMSO without anesthetic, without improvement because of bad tolerance and no possibility to have a one hour contact between the bladder and the DMSO. The 11 patients were evaluated by mictional calendar and Sant O'Leary score. All the patients had a hydrodistension and a per os treatment without improvement. Six new iDMSO were performed under general anesthetic in ambulatory surgery with good tolerance for the 11 patients. The frequency and the nocturia before iDMSO without anesthetic and after iDMSO under general anesthetic were 32.2minutes [15; 60] and 6.3 per night [3; 10] and 126.9minutes [25; 240] and 3 per night [2; 6], so a variation respectively of 96.4minutes [0; 180] and of 3.75 per night [2; 6]. The symptom score and the problem index were 17.5 [13; 20] and 15.5 [13; 16] before and 13.5 [4; 20] and 12 [1; 16] after iDMSO under general anesthetic; a variation of 3.2 [0; 9] and 4 [0; 12]. The iDMSO under general anesthetic seems to improve objectively and subjectively the patients who are not improved by the instillations without anesthetic because of bad tolerance. 4. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  1. Electromagnetic field in control tissue regeneration, pelvic pain, neuro-inflammation and modulation of non-neuronal cells.

    Science.gov (United States)

    Aragona, S E; Mereghetti, G; Lotti, J; Vosa, A; Lotti, T; Canavesi, E

    In scientific literature, magnetic fields are used both in basic science and clinical research. They are often used to treat pain and neuro-inflammation disorders thanks to their influence on cellular responses. Our project was born from the regenerative support that we wanted to give to those diseases characterized by neuro-inflammation, nerve lesion, muscles and tissues disorders that can transform the symptom (e.g. neuropathic pelvic pain) in disease. In this study, we examined the action of pulsed electromagnetic fields (PEMFs) on skin lesion regeneration and the repetitive trans-pelvic magnetic stimulation (rTPMS) on patients affected by incontinence and post-surgical problems, sexual dysfunction, and pelvic pain. In rTPMS for post-surgery urinary incontinence, 40 patients affected by post-surgery urinary incontinence were enrolled. Twenty patients (post-prostatectomy) were treated with rTPMS and 20 with conventional therapies. In PEMF for the regeneration of skin tissue, 50 patients affected by various types of skin lesions (70% low legs vascular lesions) were treated with pulsed electromagnetic fields (PEMFs) twice per week and subsequently with home treatment (Home Care device) twice per day. In rTPMS study, results were evaluated after 3 months. In 10 patients (7 post prostatectomy, 3 cystourethrocele) which were submitted to 18 sessions, twice a week, an improvement of incontinence in 75% of cases with patient compliance was recorded and the quality of life up to 100% also improved. Utilizing PEMFs for the regeneration of skin tissue, following 3 months of AIMED protocol treatment, we reached a reduction of 50% of lesion area in the 60% of cases; 35% of cases healed completely. The use of rTPMS allows training muscles to adequately respond to inflammatory stimulus that causes muscle accommodation deficits with altered contractility or spastic painful contracture in pelvic district. It also stimulates a series of regenerative phenomena due to the action of

  2. 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......, and EMG activity in the VM and VL muscles was reduced. Compressive forces, adduction moments, knee joint kinematics, and hamstring EMG activity were unaffected by pain. Interestingly, the observed changes persisted when the pain had vanished. The results demonstrate that muscle pain modulated the function...

  3. Facing the experience of pain: A neuropsychological perspective

    Science.gov (United States)

    Fabbro, Franco; Crescentini, Cristiano

    2014-09-01

    Pain is an experience that none of us would like to have but that each one of us is destined to experience in our lives. Despite its pervasiveness, the experience of pain remains problematic and complex in its depth. Pain is a multidimensional experience that involves nociception as well as emotional and cognitive aspects that can modulate its perception. Following a brief discussion of the neurobiological mechanisms underlying pain, the purpose of this review is to discuss the main psychological, neuropsychological, cultural, and existential aspects which are the basis of diverse forms of pain, like the pain of separation from caregivers or from ourselves (e.g., connected to the thought of our death), the suffering that we experience observing other people's pain, the pain of change and the existential pain connected to the temporal dimension of the mind. Finally, after a discussion of how the mind is able to not only create but also alleviate the pain, through mechanisms such as the expectation of the treatment and the hope of healing, we conclude by discussing neuropsychological research data and the attitude promoted by mindfulness meditation in relation to the pain. An attitude in which, instead to avoid and reject the pain, one learns to face mindfully the experience of pain.

  4. The Role of the Periaqueductal Gray in the Modulation of Pain in Males and Females: Are the Anatomy and Physiology Really that Different?

    Directory of Open Access Journals (Sweden)

    Dayna R. Loyd

    2009-01-01

    Full Text Available Anatomical and physiological studies conducted in the 1960s identified the periaqueductal gray (PAG and its descending projections to the rostral ventromedial medulla (RVM and spinal cord dorsal horn, as a primary anatomical pathway mediating opioid-based analgesia. Since these initial studies, the PAG-RVM-spinal cord pathway has been characterized anatomically and physiologically in a wide range of vertebrate species. Remarkably, the majority of these studies were conducted exclusively in males with the implicit assumption that the anatomy and physiology of this circuit were the same in females; however, this is not the case. It is well established that morphine administration produces greater antinociception in males compared to females. Recent studies indicate that the PAG-RVM pathway contributes to the sexually dimorphic actions of morphine. This manuscript will review our anatomical, physiological, and behavioral data identifying sex differences in the PAG-RVM pathway, focusing on its role in pain modulation and morphine analgesia.

  5. Grid Voltage Modulated Control of Grid-Connected Voltage Source Inverters under Unbalanced Grid Conditions

    DEFF Research Database (Denmark)

    Li, Mingshen; Gui, Yonghao; Quintero, Juan Carlos Vasquez

    2017-01-01

    In this paper, an improved grid voltage modulated control (GVM) with power compensation is proposed for grid-connected voltage inverters when the grid voltage is unbalanced. The objective of the proposed control is to remove the power ripple and to improve current quality. Three power compensation...

  6. A Comparison of the 2/3/5 Selective Positive Allosteric Modulators L-838,417 and TPA023 in Preclinical Models of Inflammatory and Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Sarah Nickolls

    2011-01-01

    Full Text Available GABAA receptors containing α2/3 subunits are current targets in the battle to develop new pain medications, as they are expressed in the spinal cord where increasing inhibitory drive should result in analgesia. However, this approach is prone to a range of side effects including sedation, cognitive impairment, and abuse as a consequence of the widespread influence of GABA. The ability to make subtype selective low-efficacy benzodiazepine compounds, which potentiate the action of GABA at specific α subunits, has the potential to reduce this side effect profile. In this study, we have investigated the effects of the medium-efficacy positive allosteric modulator (PAM L-838,417 and the low-efficacy PAM TPA023 in a number of preclinical inflammatory and neuropathic pain models. We conclude that either the higher level of efficacy at α2/3 or efficacy at α5 is required for compounds to have a significant analgesic effect in a range of models, and, therefore, although the side-effect profile of compounds can be reduced compared to typical benzodiazepines, it is unlikely that it can be completely eliminated.

  7. Role of ventrolateral orbital cortex muscarinic and nicotinic receptors in modulation of capsaicin-induced orofacial pain-related behaviors in rats.

    Science.gov (United States)

    Tamaddonfard, Esmaeal; Erfanparast, Amir; Abbas Farshid, Amir; Delkhosh-Kasmaie, Fatmeh

    2017-11-15

    Acetylcholine, as a major neurotransmitter, mediates many brain functions such as pain. This study was aimed to investigate the effects of microinjection of muscarinic and nicotinic acetylcholine receptor antagonists and agonists into the ventrolateral orbital cortex (VLOC) on capsaicin-induced orofacial nociception and subsequent hyperalgesia. The right side of VLOC was surgically implanted with a guide cannula in anaesthetized rats. Orofacial pain-related behaviors were induced by subcutaneous injection of a capsaicin solution (1.5µg/20µl) into the left vibrissa pad. The time spent face rubbing with ipsilateral forepaw and general behavior were recorded for 10min, and then mechanical hyperalgesia was determined using von Frey filaments at 15, 30, 45 and 60min post-capsaicin injection. Alone intra-VLOC microinjection of atropine (a muscarinic acetylcholine receptor antagonist) and mecamylamine (a nicotinic acetylcholine receptor antagonist) at a similar dose of 200ng/site did not alter nocifensive behavior and hyperalgesia. Microinjection of oxotremorine (a muscarinic acetylcholine receptor agonist) at doses of 50 and 100ng/site and epibatidine (a nicotinic acetylcholine receptor agonist) at doses of 12.5, 25, 50 and 100ng/site into the VLOC suppressed pain-related behaviors. Prior microinjections of 200ng/site atropine and mecamylamine (200ng/site) prevented oxotremorine (100ng/site)-, and epibatidine (100ng/site)-induced antinociception, respectively. None of the above-mentioned chemicals changed general behavior. These results showed that the VLOC muscarinic and nicotinic acetylcholine receptors might be involved in modulation of orofacial nociception and hypersensitivity. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. PSD95 gene specific siRNAs attenuate neuropathic pain through modulating neuron sensibility and postsynaptic CaMKIIα phosphorylation.

    Science.gov (United States)

    Le, Shen; Xu, Li; Wen, Chen; Li, Xu; Wei, Liu; Xue-rong, Yu; Yu-guang, Huang

    2011-12-01

    To observe the effects of PSD95 gene specific siRNAs on neuropathic pain relief, neuron viability, and postsynaptic calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) phosphorylation in vitro and in vivo. Gene-specific siRNAs of rat PSD95 were synthesized chemically for transfection. Adult male Sprague-Dawley (SD) rats were randomly divided into 3 groups: naïve group (n=6), sham group (n=6), and sciatic nerve chronic constriction injury (CCI) group (n=24). The CCI group was further divided into 4 groups (n=6 in each group), which were pretreated with normal saline, transfection vehicle, negative control siRNAs, and PSD95 gene specific siRNAs respectively. All the subgroups received corresponding agents intrathecally for 3 days, started one day before the CCI of sciatic nerve. Both mechanical allodynia and thermal hyperalgesia were measured on post-operative day 3 and 7. PSD95 gene silenced NG108-15 cells were further stimulated by glutamate, with the cell viability and the expression/phosphorylation of CaMKIIα measured by MTT cell proliferation assay and Western blot, respectively. The siRNAs decreased PSD95 mRNA level significantly both in vivo and in vitro. Neuropathic pain rats pretreated with PSD95 gene specific siRNAs exhibited significant elevation in the mechanical withdrawal threshold and paw withdrawal thermal latency, without affecting the baseline nociception. PSD95 gene silencing enhanced neuronal tolerance against the glutamate excitotoxicity, meanwhile the phosphorylation of CaMKIIα Thr286 was attenuated. Pre-emptive administration of PSD95 gene specific siRNAs may attenuate the central sensitization CaMKIIα-related signaling cascades, leading to the relief of neuropathic pain.

  9. MANAGEMENT OF ACUTE MUSCULOSKELETAL PAIN ...

    African Journals Online (AJOL)

    of multimodal and multi-agent approach to acute pain management for better patient care. ... injuries and surgical operations leave a huge burden .... Pain under treatment. There are multiple reasons for pain under treatment which include medical personnel lacking formal education on pain management; inadequate pain.

  10. Glia and pain: is chronic pain a gliopathy?

    Science.gov (United States)

    Ji, Ru-Rong; Berta, Temugin; Nedergaard, Maiken

    2013-12-01

    Activation of glial cells and neuro-glial interactions are emerging as key mechanisms underlying chronic pain. Accumulating evidence has implicated 3 types of glial cells in the development and maintenance of chronic pain: microglia and astrocytes of the central nervous system (CNS), and satellite glial cells of the dorsal root and trigeminal ganglia. Painful syndromes are associated with different glial activation states: (1) glial reaction (ie, upregulation of glial markers such as IBA1 and glial fibrillary acidic protein (GFAP) and/or morphological changes, including hypertrophy, proliferation, and modifications of glial networks); (2) phosphorylation of mitogen-activated protein kinase signaling pathways; (3) upregulation of adenosine triphosphate and chemokine receptors and hemichannels and downregulation of glutamate transporters; and (4) synthesis and release of glial mediators (eg, cytokines, chemokines, growth factors, and proteases) to the extracellular space. Although widely detected in chronic pain resulting from nerve trauma, inflammation, cancer, and chemotherapy in rodents, and more recently, human immunodeficiency virus-associated neuropathy in human beings, glial reaction (activation state 1) is not thought to mediate pain sensitivity directly. Instead, activation states 2 to 4 have been demonstrated to enhance pain sensitivity via a number of synergistic neuro-glial interactions. Glial mediators have been shown to powerfully modulate excitatory and inhibitory synaptic transmission at presynaptic, postsynaptic, and extrasynaptic sites. Glial activation also occurs in acute pain conditions, and acute opioid treatment activates peripheral glia to mask opioid analgesia. Thus, chronic pain could be a result of "gliopathy," that is, dysregulation of glial functions in the central and peripheral nervous system. In this review, we provide an update on recent advances and discuss remaining questions. Copyright © 2013 International Association for the

  11. Analysis of piezoelectric energy harvester under modulated and filtered white Gaussian noise

    Science.gov (United States)

    Quaranta, Giuseppe; Trentadue, Francesco; Maruccio, Claudio; Marano, Giuseppe C.

    2018-05-01

    This paper proposes a comprehensive method for the electromechanical probabilistic analysis of piezoelectric energy harvesters subjected to modulated and filtered white Gaussian noise (WGN) at the base. Specifically, the dynamic excitation is simulated by means of an amplitude-modulated WGN, which is filtered through the Clough-Penzien filter. The considered piezoelectric harvester is a cantilever bimorph modeled as Euler-Bernoulli beam with a concentrated mass at the free-end, and its global behavior is approximated by the fundamental vibration mode (which is tuned with the dominant frequency of the dynamic input). A resistive electrical load is considered in the circuit. Once the Lyapunov equation of the coupled electromechanical problem has been formulated, an original and efficient semi-analytical procedure is proposed to estimate mean and standard deviation of the electrical energy extracted from the piezoelectric layers.

  12. The drug candidate, ADX71441, is a novel, potent and selective positive allosteric modulator of the GABABreceptor with a potential for treatment of anxiety, pain and spasticity.

    Science.gov (United States)

    Kalinichev, Mikhail; Girard, Françoise; Haddouk, Hasnaà; Rouillier, Mélanie; Riguet, Eric; Royer-Urios, Isabelle; Mutel, Vincent; Lütjens, Robert; Poli, Sonia

    2017-03-01

    Positive allosteric modulation of the GABA B receptor is a promising alternative to direct activation of the receptor as a therapeutic approach for treatment of addiction, chronic pain, anxiety, epilepsy, autism, Fragile X syndrome, and psychosis. Here we describe in vitro and in vivo characterization of a novel, potent and selective GABA B positive allosteric modulator (PAM) N-(5-(4-(4-chloro-3-fluorobenzyl)-6-methoxy-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)-2-fluorophenyl)acetamide (ADX71441). In vitro, Schild plot and reversibility tests at the target confirmed PAM properties of the compound. In mice and rats ADX71441 is bioavailable after oral administration and is brain penetrant. A single dose of ADX71441 had an anxiolytic-like profile in the mouse marble burying test (minimum effective dose; MED 3 mg/kg) as well as in the elevated plus maze test in mice and rats (both MED 3 mg/kg). Also, in mice, acute administration of ADX71441 reduced visceral pain-associated behaviors in the acetic acid-induced writhing test. ADX71441 dose-dependently reduced time on rotarod in rats (MED 10 mg/kg) indicative of muscle-relaxant qualities. ADX71441 reduced locomotor activity in mice (10 mg/kg) and rats (3 mg/kg) after single dose; however, following sub-chronic administration in mice, 30 mg/kg ADX71441 was associated with normal locomotor activity. While acute administration of ADX71441 reduced body temperature in rats and mice (both MED 10 mg/kg), the effect in the former was transient, rapidly returning to normal levels despite high concentrations of the compound remaining in plasma. Thus, the GABA B PAM ADX71441 represents a valid therapeutic approach for development of novel treatment of anxiety, pain and spasticity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Under Pressure: Applying Practice-Based Learning and Improvement to the Treatment of Chronic Neuropathic Pain in Patients with Burns.

    Science.gov (United States)

    Rapolti, Mihaela; Wu, Cindy; Schuth, Olga A; Hultman, Charles Scott

    2017-10-01

    Chronic neuropathic pain after burn injury may have multiple causes, such as direct nerve injury, nerve compression, or neuroma formation, and can significantly impair quality of life and limit functional recovery. Management includes a team-based approach that involves close collaboration between occupational and physical therapists, plastic surgeons, and experts in chronic pain, from neurology, anesthesia, psychiatry, and physiatry. Carefully selected patients with an anatomic cause of chronic neuropathic pain unequivocally benefit from surgical intervention. Self-reflection and analysis yield improvement in both efficiency and effectiveness when managing patients with burns with chronic neuropathic pain. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Dead zone analysis of ECAL barrel modules under static and dynamic load

    Science.gov (United States)

    Pierre-Emile, T.; Anduze, M.

    2018-03-01

    In the context of ILD project, impact studies of environmental loads on the Electromagnetic CALorimeter (ECAL) have been initiated. The ECAL part considered is the barrel and it consists of several independent modules which are mounted on the Hadronic CALorimeter barrel (HCAL) itself mounted on the cryostat coil and the yoke. The estimate of the gap required between each ECAL modules is fundamental to define the assembly step and avoid mechanical contacts over the barrel lifetime. In the meantime, it has to be done in consideration to the dead spaces reduction and detector hermiticity optimization. Several Finite Element Analysis (FEA) with static and dynamic loads have been performed in order to define correctly the minimum values for those gaps. Due to the implantation site of the whole project in Japan, seismic analysis were carried out in addition to the static ones. This article shows results of these analysis done with the Finite Element Method (FEM) in ANSYS. First results show the impact of HCAL design on the ECAL modules motion in static load. The second study dedicated to seismic approach on a larger model (including yoke and cryostat) gives additional results on earthquake consequences.

  15. Transcranial alternating current stimulation: A review of the underlying mechanisms and modulation of cognitive processes

    Directory of Open Access Journals (Sweden)

    Christoph S Herrmann

    2013-06-01

    Full Text Available Brain oscillations of different frequencies have been associated with a variety of cognitive functions. Convincing evidence supporting those associations has been provided by studies using intracranial stimulation, pharmacological interventions and lesion studies. The emergence of novel non-invasive brain stimulation techniques like repetitive transcranial magnetic stimulation (rTMS and transcranial alternating current stimulation (tACS now allows to modulate brain oscillations directly. Particularly, tACS offers the unique opportunity to causally link brain oscillations of a specific frequency range to cognitive processes, because it uses sinusoidal currents that are bound to one frequency only. Using tACS allows to modulate brain oscillations and in turn to influence cognitive processes, thereby demonstrating the causal link between the two. Here, we review findings about the physiological mechanism of tACS and studies that have used tACS to modulate basic motor and sensory processes as well as higher cognitive processes like memory, ambiguous perception, and decision making.

  16. Differences in Pain Processing Between Patients with Chronic Low Back Pain, Recurrent Low Back Pain, and Fibromyalgia.

    Science.gov (United States)

    Goubert, Dorien; Danneels, Lieven; Graven-Nielsen, Thomas; Descheemaeker, Filip; Meeus, Mira

    2017-05-01

    The impairment in musculoskeletal structures in patients with low back pain (LBP) is often disproportionate to their complaint. Therefore, the need arises for exploration of alternative mechanisms contributing to the origin and maintenance of non-specific LBP. The recent focus has been on central nervous system phenomena in LBP and the pathophysiological mechanisms underlying the various symptoms and characteristics of chronic pain. Knowledge concerning changes in pain processing in LBP remains ambiguous, partly due to the diversity in the LBP population. The purpose of this study is to compare quantitative sensory assessment in different groups of LBP patients with regard to chronicity. Recurrent low back pain (RLBP), mild chronic low back pain (CLBP), and severe CLBP are compared on the one hand with healthy controls (HC), and on the other hand with fibromyalgia (FM) patients, in which abnormal pain processing has previously been reported. Cross-sectional study. Department of Rehabilitation Sciences, Ghent University, Belgium. Twenty-three RLBP, 15 mild CLBP, 16 severe CLBP, 26 FM, and 21 HC participated in this study. Quantitative sensory testing was conducted by manual pressure algometry and computer-controlled cuff algometry. A manual algometer was used to evaluate hyperalgesia as well as temporal summation of pain and a cuff algometer was used to evaluate deep tissue hyperalgesia, the efficacy of the conditioned pain modulation and spatial summation of pain. Pressure pain thresholds by manual algometry were significantly lower in FM compared to HC, RLBP, and severe CLBP. Temporal summation of pain was significantly higher in FM compared to HC and RLBP. Pain tolerance thresholds assessed by cuff algometry were significantly lower in FM compared to HC and RLBP and also in severe CLBP compared to RLBP. No significant differences between groups were found for spatial summation or conditioned pain modulation. No psychosocial issues were taken into account for this

  17. Pharmacologic management of neuropathic pain.

    Science.gov (United States)

    Gordon, Debra B; Love, Georgette

    2004-12-01

    The mechanisms underlying the pathogenesis of neuropathic pain are complex but are gradually coming to light. Agents that have been found effective in a variety of neuropathic pain conditions include drugs that act to modulate (a) sodium or calcium channels, (b) N-methyl-D-aspartate receptors, (c) norepinephrine or serotonin reuptake, (d) opioid receptors, and (e) other cellular processes. Clinical trials have primarily evaluated these treatments for postherpetic neuralgia and painful diabetic neuropathy, the two most common types of neuropathic pain. Nonetheless, the identification of effective treatment regimens remains challenging, often because multiple mechanisms may be operating in a given patient giving rise to the same symptom. Alternatively, a single mechanism may be responsible for multiple symptoms. Currently available diagnostic tools are inadequate to determine the best treatment using a mechanism-based model. Clinically, drug treatment of neuropathic pain is often a matter of treatment trials. This article presents a summary of available clinical information on first-line and lesser-known treatments for neuropathic pain.

  18. Mechanisms underlying the noradrenergic modulation of longitudinal coordination during swimming in Xenopus laevis tadpoles

    DEFF Research Database (Denmark)

    Merrywest, Simon D; McDearmid, Jonathan R; Kjaerulff, Ole

    2003-01-01

    Noradrenaline (NA) is a potent modulator of locomotion in many vertebrate nervous systems. When Xenopus tadpoles swim, waves of motor neuron activity alternate across the body and propagate along it with a brief rostro-caudal delay (RC-delay) between segments. We have now investigated...... might promote postinhibitory rebound firing. The synaptic inputs during swimming were simulated using a sustained positive current, superimposed upon which were brief negative currents. When these conditions were held constant NA enhanced the probability of rebound firing--indicating a direct effect...

  19. Performance Analysis of Thermoelectric Modules Consisting of Square Truncated Pyramid Elements Under Constant Heat Flux

    Science.gov (United States)

    Oki, Sae; Natsui, Shungo; Suzuki, Ryosuke O.

    2018-01-01

    System design of a thermoelectric (TE) power generation module is pursued in order to improve the TE performance. Square truncated pyramid shaped P-N pairs of TE elements are connected electronically in series in the open space between two flat insulator boards. The performance of the TE module consisting of 2-paired elements is numerically simulated using commercial software and original TE programs. Assuming that the heat radiating into the hot surface is regulated, i.e., the amount of heat from the hot surface to the cold one is steadily constant, as it happens for solar radiation heating, the performance is significantly improved by changing the shape and the alignment pattern of the elements. When the angle θ between the edge and the base is smaller than 72°, and when the cold surface is kept at a constant temperature, two patterns in particular, amongst the 17 studied, show the largest TE power and efficiency. In comparison to other geometries, the smarter square truncated pyramid shape can provide higher performance using a large cold bath and constant heat transfer by heat radiation.

  20. [Progress in study on endocannabinoids and cannabinoid receptors in the treatment for neuropathic pain].

    Science.gov (United States)

    Liu, Peng; Zhang, Wei; Zhang, Shaobo; Zhang, Yibao; Wang, Jing

    2016-08-01

    Endocannabinoids and cannabinoid receptors are expressed in various central pain modulation regions. They maintain in dynamic changes in the expression level and distribution under different pathological and physiological conditions. These changes possess advantage as well as disadvantage. Exogenous administration of endocannabinoids exerts analgesic effect in different pain models, which is mainly mediated by the cannabinoid CB1 and CB2 receptors. Inhibition of enzymes for degrading endocannabinoids in different pain models also shows analgesic effect due to the increased local levels of endocannabinoids.

  1. Neurophysiological processes underlying the phantom limb pain experience and the use of hypnosis in its clinical management: an intensive examination of two patients.

    Science.gov (United States)

    Rosén, G; Willoch, F; Bartenstein, P; Berner, N; Røsjø, S

    2001-01-01

    In a pilot study with 2 patients suffering from phantom limb pain (PLP), hypnotic suggestions were used to modify and control the experience of the phantom limb, and positron emission tomography (PET) was used to index underlying pathways and areas involved in the processing of phantom limb experience (PLE) and PLP. The patients' subjective experiences of pain were recorded in a semistructured protocol. PET results demonstrated activation in areas known to be responsible for sensory and motor processing. The reported subjective experiences of PLP and movement corresponded with predicted brain activity patterns. This work helps to clarify the central nervous system correlates of phantom limb sensations, including pain. It further suggests that hypnosis can be incorporated into treatment protocols for PLP.

  2. Chronic pain after hysterectomy

    DEFF Research Database (Denmark)

    Brandsborg, B.; Nikolajsen, L.; Kehlet, H.

    2008-01-01

    BACKGROUND: Chronic pain is a well-known adverse effect of surgery, but the risk of chronic pain after gynaecological surgery is less established. METHOD: This review summarizes studies on chronic pain following hysterectomy. The underlying mechanisms and risk factors for the development of chronic...... post-hysterectomy pain are discussed. RESULTS AND CONCLUSION: Chronic pain is reported by 5-32% of women after hysterectomy. A guideline is proposed for future prospective studies Udgivelsesdato: 2008/3...

  3. The expression of spinal methyl-CpG-binding protein 2, DNA methyltransferases and histone deacetylases is modulated in persistent pain states

    Directory of Open Access Journals (Sweden)

    Tochiki Keri K

    2012-02-01

    Full Text Available Abstract Background DNA CpG methylation is carried out by DNA methyltransferases and induces chromatin remodeling and gene silencing through a transcription repressor complex comprising the methyl-CpG-binding protein 2 (MeCP2 and a subset of histone deacetylases. Recently, we have found that MeCP2 activity had a crucial role in the pattern of gene expression seen in the superficial dorsal horn rapidly after injection of Complete Freund's Adjuvant (CFA in the rat ankle joint. The aim of the present study was to analyse the changes in expression of MeCP2, DNA methyltransferases and a subset of histone deacetylases in the superficial dorsal horn during the maintenance phase of persistent pain states. In this process, the cell specific expression of MeCP2 was also investigated. Results Using immunohistochemistry, we found that neurones, oligodendrocytes and astrocytes expressed MeCP2. Microglia, oligodendrocyte precursor cells and Schwann cells never showed any positive stain for MeCP2. Quantitative analyses showed that MeCP2 expression was increased in the superficial dorsal horn 7 days following CFA injection in the ankle joint but decreased 7 days following spared nerve injury. Overall, the expression of DNA methyltransferases and a subset of histone deacetylases followed the same pattern of expression. However, there were no significant changes in the expression of the MeCP2 targets that we had previously shown are regulated in the early time points following CFA injection in the ankle joint. Finally, the expression of MeCP2 was also down regulated in damaged dorsal root ganglion neurones following spared nerve injury. Conclusion Our results strongly suggest that changes in chromatin compaction, regulated by the binding of MeCP2 complexes to methylated DNA, are involved in the modulation of gene expression in the superficial dorsal horn and dorsal root ganglia during the maintenance of persistent pain states.

  4. Glia and pain: Is chronic pain a gliopathy?

    Science.gov (United States)

    Ji, Ru-Rong; Berta, Temugin; Nedergaard, Maiken

    2013-01-01

    Activation of glial cells and neuro-glial interactions are emerging as key mechanisms underlying chronic pain. Accumulating evidence has implicated 3 types of glial cells in the development and maintenance of chronic pain: microglia and astrocytes of the central nervous system (CNS), and satellite glial cells of the dorsal root and trigeminal ganglia. Painful syndromes are associated with different glial activation states: (1) glial reaction (ie, upregulation of glial markers such as IBA1 and glial fibrillary acidic protein (GFAP) and/or morphological changes, including hypertrophy, proliferation, and modifications of glial networks); (2) phosphorylation of mitogen-activated protein kinase signaling pathways; (3) upregulation of adenosine triphosphate and chemokine receptors and hemichannels and downregulation of glutamate transporters; and (4) synthesis and release of glial mediators (eg, cytokines, chemokines, growth factors, and proteases) to the extracellular space. Although widely detected in chronic pain resulting from nerve trauma, inflammation, cancer, and chemotherapy in rodents, and more recently, human immunodeficiency virus-associated neuropathy in human beings, glial reaction (activation state 1) is not thought to mediate pain sensitivity directly. Instead, activation states 2 to 4 have been demonstrated to enhance pain sensitivity via a number of synergistic neuro-glial interactions. Glial mediators have been shown to powerfully modulate excitatory and inhibitory synaptic transmission at presynaptic, postsynaptic, and extrasynaptic sites. Glial activation also occurs in acute pain conditions, and acute opioid treatment activates peripheral glia to mask opioid analgesia. Thus, chronic pain could be a result of “gliopathy,” that is, dysregulation of glial functions in the central and peripheral nervous system. In this review, we provide an update on recent advances and discuss remaining questions. PMID:23792284

  5. [Hindfoot pain].

    Science.gov (United States)

    Damiano, Joël; Bouysset, Maurice

    2010-03-20

    The hindfoot is the part of the foot which is proximal to the midtarsal joint. The obvious causes of pain are not considered (post-traumatic etiologies, sprains and fractures but also cutaneous lesions). The main etiologies on the subject are successively exposed by following the localization of the pain. Diffuse pains (ankle arthritis tarsal osteoarthritis, algodystrophy, calcaneo-navicular synostosis but also bone diseases like stress fractures, Paget disease or tumors). Plantar talalgia (Sever's disease, plantar fasciitis and entrapment neuropathies such as (esions of the medial calcaneal nerve, of the first branch of the plantar lateral nerve, medial plantar nerve and lateral plantar nerve). Posterior pains: calcaneal tendinopathy including peritendinitis, tendinosis, retro-calcaneal bursitis and pathology of the postero-lateral talar tuberosity. Medial pains: tendinopathies of the posterior tibial tendon and tendinopathy of the flexor hallucis longus tendon and tarsal tunnel syndrome. Lateral pains: fibularis tendinopathies including split lesions of the fibularis brevis tendon, displacement of the fibularis iongus tendon, sinus tarsi syndrome and finally thickenings of capsules and ligaments and ossifications localized under the tibial malleoli. Anterior pains: antero-inferior tibio-fibular ligament, anterior tibial tendinopathy and anterior impingment syndrome.

  6. Epidural injections for back pain

    Science.gov (United States)

    ESI; Spinal injection for back pain; Back pain injection; Steroid injection - epidural; Steroid injection - back ... pillow under your stomach. If this position causes pain, you either sit up or lie on your ...

  7. Effects of eye movement desensitization and reprocessing (EMDR) on non-specific chronic back pain: a randomized controlled trial with additional exploration of the underlying mechanisms.

    Science.gov (United States)

    Tesarz, Jonas; Gerhardt, Andreas; Leisner, Sabine; Janke, Susanne; Hartmann, Mechthild; Seidler, Günther H; Eich, Wolfgang

    2013-08-30

    Non-specific chronic back pain (CBP) is often accompanied by psychological trauma, but treatment for this associated condition is often insufficient.Nevertheless, despite the common co-occurrence of pain and psychological trauma, a specific trauma-focused approach for treating CBP has been neglected to date. Accordingly, eye movement desensitization and reprocessing (EMDR), originally developed as a treatment approach for posttraumatic stress disorders, is a promising approach for treating CBP in patients who have experienced psychological trauma.Thus, the aim of this study is to determine whether a standardized, short-term EMDR intervention added to treatment as usual (TAU) reduces pain intensity in CBP patients with psychological trauma vs. TAU alone. The study will recruit 40 non-specific CBP patients who have experienced psychological trauma. After a baseline assessment, the patients will be randomized to either an intervention group (n = 20) or a control group (n = 20). Individuals in the EMDR group will receive ten 90-minute sessions of EMDR fortnightly in addition to TAU. The control group will receive TAU alone. The post-treatment assessments will take place two weeks after the last EMDR session and six months later.The primary outcome will be the change in the intensity of CBP within the last four weeks (numeric rating scale 0-10) from the pre-treatment assessment to the post-treatment assessment two weeks after the completion of treatment.In addition, the patients will undergo a thorough assessment of the change in the experience of pain, disability, trauma-associated distress, mental co-morbidities, resilience, and quality of life to explore distinct treatment effects. To explore the mechanisms of action that are involved, changes in pain perception and pain processing (quantitative sensory testing, conditioned pain modulation) will also be assessed.The statistical analysis of the primary outcome will be performed on an intention-to-treat basis

  8. The effect of preoperative administration of morphine in alleviating intraoperative pain of percutaneous transforaminal endoscopic discectomy under local anesthesia: A STROBE compliant study.

    Science.gov (United States)

    Fan, Yunshan; Gu, Guangfei; Fan, Guoxin; Zhu, Yanjie; Yang, Yitao; Gu, Xin; Zhang, Hailong; He, Shisheng

    2017-10-01

    Local anesthesia is routinely recommended for percutaneous transforaminal endoscopic discectomy (PTED). However, the intense intraoperative pain remains a serious problem. The purpose of the current study is to find a safe and effective method to alleviate the intense pain during PTED for lumbar disc herniation (LDH) under local anesthesia.This study retrospectively analyzed 63 LDH patients who accepted PTED under local anesthesia. Thirty-one patients received intramuscular injection of morphine before PTED, while the other 32 were not. The 10 points visual analogue scale (VAS) was used to assess the patients' maximum leg and back pain. Patients were asked to grade their experiences of surgery and anesthesia on a 5-point Likert-type scale after the surgery. Modified Mac Nab Criteria were used to evaluate the surgical outcomes after 3-month follow-up.The intraoperative VAS scores of patients who accepted preoperative intervention decreased significantly. The postoperative VAS scores of both groups showed no significance. Patients who received preoperative intervention reported a higher subjective satisfaction rate with the surgery experience. According to the Modified Mac Nab criteria, the surgical outcomes of both groups were similar through the 3-month follow-up. After injection of morphine, 4 patients complained nausea and 2 patients experienced vomiting.Preoperative intramuscular injection of morphine could reduce the patients' pain during the PTED surgery and improve the patients' satisfaction without affecting the surgical outcome. Except for a higher incidence of nausea and vomiting, this method is relatively safe and convenient.

  9. Life cycle of Arabidopsis thaliana under microgravity condition in the International Space Station Kibo module

    Science.gov (United States)

    Karahara, Ichirou; Soga, Kouichi; Hoson, Takayuki; Kamisaka, Seiichiro; Yano, Sachiko; Shimazu, Toru; Tamaoki, Daisuke; Tanigaki, Fumiaki; Kasahara, Haruo; Yashiro, Umi; Suto, Takamichi; Yamaguchi, Takashi; Kasahara, Hirokazu

    2012-07-01

    Gravity is an important environmental factors for growth and development of plants throughout their life cycle. We have designed an experiment, which is called Space Seed, to examine the effects of microgravity on the seed to seed life cycle of plants. We have carried out this experiment using a newly developed apparatus, which is called the Plant Experiment Unit (PEU) and installed in the Cell Biology Experiment Facility (CBEF) onboard International Space Station (ISS). The CBEF is equipped with a turntable generating artificial gravity to perform 1-G control experiment as well as micro-G experiment on board. Arabidopsis thaliana seeds sown on dry rockwool in PEUs were transported from Kennedy Space Center to the ISS Kibo module by Space Shuttle Discovery in STS-128 mission. This experiment was started on Sep. 10, 2009 and terminated on Nov. 11, 2009. Arabidopsis seeds successfully germinated, and the plants passed through both vegetative and reproductive processes, such as formation of rosette leaves, bolting of inflorescence stems, flowering, formation of siliques and seeds. Vegetative and reproductive growth were compared among micro-G plants, 1-G control, and the ground control.

  10. Flow angle dependent photoacoustic Doppler power spectra under intensity-modulated continuous wave laser excitation

    Directory of Open Access Journals (Sweden)

    Yu Tong

    2016-02-01

    Full Text Available Photoacoustic Doppler (PAD power spectra showing an evident Doppler shift represent the major characteristics of the continuous wave-excited or burst wave-excited versions of PAD flow measurements. In this paper, the flow angle dependences of the PAD power spectra are investigated using an experiment setup that was established based on intensity-modulated continuous wave laser excitation. The setup has an overall configuration that is similar to a previously reported configuration, but is more sophisticated in that it accurately aligns the laser illumination with the ultrasound detection process, and in that it picks up the correct sample position. In the analysis of the power spectra data, we find that the background power spectra can be extracted by combining the output signals from the two channels of the lock-in amplifier, which is very useful for identification of the PAD power spectra. The power spectra are presented and analyzed in opposite flow directions, at different flow speeds, and at different flow angles. The power spectra at a 90° flow angle show the unique properties of symmetrical shapes due to PAD broadening. For the other flow angles, the smoothed power spectra clearly show a flow angle cosine relationship.

  11. 28-Homobrassinolide Modulate Antenna Complexes and Carbon Skeleton of Brassica juncea L. under Temperature Stress

    Directory of Open Access Journals (Sweden)

    Harpreet Kaur

    2014-08-01

    Full Text Available The aim of present study was to explore the ameliorative impact of 28-homoBL on morpho-physiological attributes, photosynthetic pigments and sugars of Brassica juncea L. exposed to oxidative stress caused by extreme temperatures (4 and 44 °C. For this, experiments were carried out at the Plant Physiology Laboratory, Department of Botany, Punjabi University, Patiala. Effect of different degrees of temperature (4 and 44 °C taking 24 °C as control was studied. 28-homoBL (10-6, 10-9 and 10-12M primed and unprimed seeds of B. juncea L. in terms of antenna complexes and end products of photosynthesis that is total carbohydrates and total soluble sugars was investigated. All concentrations of 28-homoBL used in present study showed different effects on morphology and light quenching pigments. All concentrations of 28-homoBL showed promoting effect on growth and light quenching pigments. The carbon makeup ameliorated positively in stressed and non-stressed components of photosynthetic machinery and 10-9 M 28-homoBL showed best results. In conclusion 28-homoBL showed great potential in protecting the reaction centre of photosynthetic machinery from oxidative stress caused by extreme low and high temperatures but in very dose dependent manner and thus modulate the carbon skeleton of the plant.

  12. A Differential Evolution Based MPPT Method for Photovoltaic Modules under Partial Shading Conditions

    Directory of Open Access Journals (Sweden)

    Kok Soon Tey

    2014-01-01

    Full Text Available Partially shaded photovoltaic (PV modules have multiple peaks in the power-voltage (P-V characteristic curve and conventional maximum power point tracking (MPPT algorithm, such as perturbation and observation (P&O, which is unable to track the global maximum power point (GMPP accurately due to its localized search space. Therefore, this paper proposes a differential evolution (DE based optimization algorithm to provide the globalized search space to track the GMPP. The direction of mutation in the DE algorithm is modified to ensure that the mutation always converges to the best solution among all the particles in the generation. This helps to provide the rapid convergence of the algorithm. Simulation of the proposed PV system is carried out in PSIM and the results are compared to P&O algorithm. In the hardware implementation, a high step-up DC-DC converter is employed to verify the proposed algorithm experimentally on partial shading conditions, load variation, and solar intensity variation. The experimental results show that the proposed algorithm is able to converge to the GMPP within 1.2 seconds with higher efficiency than P&O.

  13. Spatial Attention and Temporal Expectation Under Timed Uncertainty Predictably Modulate Neuronal Responses in Monkey V1

    Science.gov (United States)

    Sharma, Jitendra; Sugihara, Hiroki; Katz, Yarden; Schummers, James; Tenenbaum, Joshua; Sur, Mriganka

    2015-01-01

    The brain uses attention and expectation as flexible devices for optimizing behavioral responses associated with expected but unpredictably timed events. The neural bases of attention and expectation are thought to engage higher cognitive loci; however, their influence at the level of primary visual cortex (V1) remains unknown. Here, we asked whether single-neuron responses in monkey V1 were influenced by an attention task of unpredictable duration. Monkeys covertly attended to a spot that remained unchanged for a fixed period and then abruptly disappeared at variable times, prompting a lever release for reward. We show that monkeys responded progressively faster and performed better as the trial duration increased. Neural responses also followed monkey's task engagement—there was an early, but short duration, response facilitation, followed by a late but sustained increase during the time monkeys expected the attention spot to disappear. This late attentional modulation was significantly and negatively correlated with the reaction time and was well explained by a modified hazard function. Such bimodal, time-dependent changes were, however, absent in a task that did not require explicit attentional engagement. Thus, V1 neurons carry reliable signals of attention and temporal expectation that correlate with predictable influences on monkeys' behavioral responses. PMID:24836689

  14. Magnitude-dependent proliferation and contractility modulation of human bladder smooth muscle cells under physiological stretch.

    Science.gov (United States)

    Luo, De-Yi; Wazir, Romel; Du, Caigan; Tian, Ye; Yue, Xuan; Wei, Tang-Qiang; Wang, Kun-Jie

    2015-11-01

    The purpose of this study was to describe and test a kind of stretch pattern which is based on modified BOSE BioDynamic system to produce optimum physiological stretch during bladder cycle. Moreover, we aimed to emphasize the effects of physiological stretch's amplitude upon proliferation and contractility of human bladder smooth muscle cells (HBSMCs). HBSMCs were seeded onto silicone membrane and subjected to stretch simulating bladder cycle at the range of stretches and time according to customized software on modified BOSE BioDynamic bioreactor. Morphological changes were assessed using immunofluorescence and confocal laser scanning microscope. Cell proliferation and cell viability were determined by BrdU incorporation assay and Cell Counting Kit-8, respectively. Contractility of the cells was determined using collagen gel contraction assay. RT-PCR was used to assess phenotypic and contractility markers. HBSMCs were found to show morphologically spindle-shaped and orientation at various elongations in the modified bioreactor. Stretch-induced proliferation and viability depended on the magnitude of stretch, and stretches also regulate contractility and contraction markers in a magnitude-dependent manner. We described and tested a kind of stretch pattern which delivers physiological stretch implemented during bladder cycle. The findings also showed that mechanical stretch can promote magnitude-dependent morphological, proliferative and contractile modulation of HBSMCs in vitro.

  15. Dynamics of meandering spiral waves under the modulation of a dichotomous noise

    Science.gov (United States)

    Yuan, Guoyong; Ma, Litao; Xu, Lijun; Wang, Guangrui; Yang, Shiping

    2014-04-01

    In this paper, we study the effect of a dichotomous noise on meandering spiral dynamics, and exhibit how the cycloid motion of the meandering spiral tip is destroyed by the noise. Switching on the noise does not alter the primary frequency f1 and the secondary frequency f2 in the tip motion, which is different from the case for a periodic dichotomous modulation, where f2 is changed according to two specific rules. However, the dichotomous noise leads to a decrease of the amplitudes at f1 and f2, and the rate of decrease of the amplitude at f2 is larger than that at f2 in the process of increasing the noise intensity or the correlation. The areas with small v-values (SV) are defined, and the distribution and size of the SV areas are analyzed, in order to explain and describe these results. It is also proved that spiral waves can be eliminated by the dichotomous noise with a large amplitude or correlation.

  16. [Validation of the Scale of Behavior Indicators of Pain (ESCID) in critically ill, non-communicative patients under mechanical ventilation: results of the ESCID scale].

    Science.gov (United States)

    Latorre Marco, I; Solís Muñoz, M; Falero Ruiz, T; Larrasquitu Sánchez, A; Romay Pérez, A B; Millán Santos, I

    2011-01-01

    To determine the reliability and validity of the "Scale of Behavior Indicators of Pain" (Escala de Conductas Indicadoras de Dolor: ESCID) as a tool to assess pain in the critically ill, non-communicative patients with mechanical ventilation. An observational study of development and validation of this scale as an instrument for pain measurement in ICU patients over 18 years of age, who are uncommunicative and under mechanical ventilation. Their pain was assessed with the Behavioral Pain Scale (BPS) and the ESCID simultaneously, by two independent observers, when the painful maneuvers (PM), secretion aspiration and mobilization, were applied. Measurements were obtained before, during and after the PM. A descriptive analysis of the general characteristics of the population was carried out. The reliability of the ESCID was measured through the internal consistency of each item using Cronbach's alpha. Intraobserver and interobserver concordance was measured with the repeated measurements analysis of variance test. The components of the two pain scales were compared to obtain the change between the results obtained based on time, observer and procedure. The correlation between the scales was measured with the Pearson's correlation. A total of 480 observations were obtained in 42 patients, 62% were males; age 57.33 ± 16.35 years. The most frequent ICU admission was due to infectious disease (36%) and neurological disease (35%). Glasgow Coma Scale 8.45±1.2 and Richmond Agitation-Sedation Scale -2.55±1.5. Arterial blood pressure, heart rate and respiratory rate remained stable. Cronbach's s Alpha Coefficient for ESCID ranged from 0.70-0.80. There is a good correlation between the ESCID and BPS in the three measurement points in time: Pearson's correlation: before 0.97, during 0.94 and after 0.95. ESCID is a reliable and valid tool to assess pain in critically ill, non-communicative patients under mechanical ventilation. Copyright © 2010 Elsevier España, S.L. y SEEIUC

  17. Noninvasive transcranial brain stimulation and pain.

    Science.gov (United States)

    Rosen, Allyson C; Ramkumar, Mukund; Nguyen, Tam; Hoeft, Fumiko

    2009-02-01

    Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are two noninvasive brain stimulation techniques that can modulate activity in specific regions of the cortex. At this point, their use in brain stimulation is primarily investigational; however, there is clear evidence that these tools can reduce pain and modify neurophysiologic correlates of the pain experience. TMS has also been used to predict response to surgically implanted stimulation for the treatment of chronic pain. Furthermore, TMS and tDCS can be applied with other techniques, such as event-related potentials and pharmacologic manipulation, to illuminate the underlying physiologic mechanisms of normal and pathological pain. This review presents a description and overview of the uses of two major brain stimulation techniques and a listing of useful references for further study.

  18. Role of the primary motor cortex in the maintenance and treatment of pain in fibromyalgia.

    Science.gov (United States)

    Castillo Saavedra, Laura; Mendonca, Mariana; Fregni, Felipe

    2014-09-01

    Fibromyalgia is a highly prevalent, debilitating disease, characterized by chronic widespread pain. The mechanisms underlying pain are not completely understood, but it is believed to be associated with important neuroplastic changes in pain-related neural circuits. Although the involvement of the pain matrix in fibromyalgia is well established, another area that has been found to play a role in the maintenance and treatment of chronic pain is the primary motor cortex (M1). Maladaptive plasticity of M1 is a common finding in patients with chronic pain and many studies in animal models and in human subjects have shown that modulation of the activity of this cortical area induces significant analgesic effects. Furthermore, studies in other chronic pain syndromes have found alterations in baseline characteristics of M1, including an increase in cortical excitability and an abnormally enhanced response to incoming sensory stimuli. Given these findings, we hypothesize that M1 is a major modulator of pain in fibromyalgia and therefore its baseline activity reflects this strong feedback between M1 and pain-related neural areas. However, the feedback loop between M1 and the pain matrix is not enough to decrease pain in fibromyalgia per se, thus increasing its modulatory effect by engaging this network through different behavioral and modulatory techniques is a potentially beneficial treatment for pain in fibromyalgia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Haemoglobin modulates NO emission and hyponasty under hypoxia-related stress in Arabidopsis thaliana

    Science.gov (United States)

    Hebelstrup, Kim H.

    2012-01-01

    Nitric oxide (NO) and ethylene are signalling molecules that are synthesized in response to oxygen depletion. Non-symbiotic plant haemoglobins (Hbs) have been demonstrated to act in roots under oxygen depletion to scavenge NO. Using Arabidopsis thaliana plants, the online emission of NO or ethylene was directly quantified under normoxia, hypoxia (0.1–1.0% O2), or full anoxia. The production of both gases was increased with reduced expression of either of the Hb genes GLB1 or GLB2, whereas NO emission decreased in plants overexpressing these genes. NO emission in plants with reduced Hb gene expression represented a major loss of nitrogen equivalent to 0.2mM nitrate per 24h under hypoxic conditions. Hb gene expression was greatly enhanced in flooded roots, suggesting induction by reduced oxygen diffusion. The function could be to limit loss of nitrogen under NO emission. NO reacts with thiols to form S-nitrosylated compounds, and it is demonstrated that hypoxia substantially increased the content of S-nitrosylated compounds. A parallel up-regulation of Hb gene expression in the normoxic shoots of the flooded plants may reflect signal transmission from root to shoot via ethylene and a role for Hb in the shoots. Hb gene expression was correlated with ethylene-induced upward leaf movement (hyponastic growth) but not with hypocotyl growth, which was Hb independent. Taken together the data suggest that Hb can influence flood-induced hyponasty via ethylene-dependent and, possibly, ethylene-independent pathways. PMID:22915746

  20. Modulating Conscious Movement Intention by Noninvasive Brain Stimulation and the Underlying Neural Mechanisms

    OpenAIRE

    Douglas, Zachary H.; Maniscalco, Brian; Hallett, Mark; Wassermann, Eric M.; He, Biyu J.

    2015-01-01

    Conscious intention is a fundamental aspect of the human experience. Despite long-standing interest in the basis and implications of intention, its underlying neurobiological mechanisms remain poorly understood. Using high-definition transcranial DC stimulation (tDCS), we observed that enhancing spontaneous neuronal excitability in both the angular gyrus and the primary motor cortex caused the reported time of conscious movement intention to be ∼60–70 ms earlier. Slow brain waves recorded ∼2–...

  1. Success or failure of chronic pain rehabilitation: the importance of good interaction - a qualitative study under patients and professionals.

    Science.gov (United States)

    Oosterhof, B; Dekker, J H M; Sloots, M; Bartels, E A C; Dekker, J

    2014-01-01

    The aim of this study was to explore which factors are associated with a successful treatment outcome in chronic pain patients and professionals participating in a multidisciplinary rehabilitation program, with a specific focus on the patient-professional interaction. Patients (n = 16) and professionals (n = 10) were interviewed and/or observed. The transcribed interviews and observations were analyzed and themes were described. Patients with a positive treatment outcome came to a shared understanding of their pain with their professional, demonstrated new learned behavior and were able to continue their learning process at home. Patients with a negative treatment outcome did not reach a shared understanding of their pain with their professional, were not able to change their behavior and wanted more help to achieve this. Both patient groups experienced organizational barriers within the treatment process. Factors associated with a high quality of patient-professional interaction included the patient experience of being taken seriously, the involvement of the professional with the patient, a clear explanation of the pain, and an open interaction between patient and professional. This study provides insight into factors which were related to a positively or negatively experienced outcome of pain rehabilitation. A good match within the patient-professional interaction seems essential. IMPLICATIONS OF REHABILITATION: Within chronic pain rehabilitation good didactic skills and a client-centered attitude of the professional may be helpful in order to make the patient feel being taken seriously. An assessment of the patient's learning style might lead to a better fit of the patient education and training according to an individual's learning style. Relapse might be prevented by paying special attention to the integration of new behavior within important life areas as work and sports.

  2. The endophytic fungus Piriformospora indica enhances Arabidopsis thaliana growth and modulates Na+/K+ homeostasis under salt stress conditions.

    Science.gov (United States)

    Abdelaziz, Mohamed E; Kim, Dongjin; Ali, Shawkat; Fedoroff, Nina V; Al-Babili, Salim

    2017-10-01

    The mutualistic, endophytic fungus Piriformospora indica has been shown to confer biotic and abiotic stress tolerance to host plants. In this study, we investigated the impact of P. indica on the growth of Arabidopsis plants under normal and salt stress conditions. Our results demonstrate that P. indica colonization increases plant biomass, lateral roots density, and chlorophyll content under both conditions. Colonization with P. indica under salt stress was accompanied by a lower Na + /K + ratio and less pronounced accumulation of anthocyanin, compared to control plants. Moreover, P. indica colonized roots under salt stress showed enhanced transcript levels of the genes encoding the high Affinity Potassium Transporter 1 (HKT1) and the inward-rectifying K + channels KAT1 and KAT2, which play key roles in regulating Na + and K + homeostasis. The effect of P. indica colonization on AtHKT1;1 expression was also confirmed in the Arabidopsis line gl1-HKT:AtHKT1;1 that expresses an additional AtHKT1;1 copy driven by the native promoter. Colonization of the gl1-HKT:AtHKT1;1 by P. indica also increased lateral roots density and led to a better Na + /K + ratio, which may be attributed to the observed increase in KAT1 and KAT2 transcript levels. Our findings demonstrate that P. indica colonization promotes Arabidopsis growth under salt stress conditions and that this effect is likely caused by modulation of the expression levels of the major Na + and K + ion channels, which allows establishing a balanced ion homeostasis of Na + /K + under salt stress conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. The endophytic fungus Piriformospora indica enhances Arabidopsis thaliana growth and modulates Na + /K + homeostasis under salt stress conditions

    KAUST Repository

    Abdelaziz, Mohamed Ewis

    2017-07-13

    The mutualistic, endophytic fungus Piriformospora indica has been shown to confer biotic and abiotic stress tolerance to host plants. In this study, we investigated the impact of P. indica on the growth of Arabidopsis plants under normal and salt stress conditions. Our results demonstrate that P. indica colonization increases plant biomass, lateral roots density, and chlorophyll content under both conditions. Colonization with P. indica under salt stress was accompanied by a lower Na+/K+ ratio and less pronounced accumulation of anthocyanin, compared to control plants. Moreover, P. indica colonized roots under salt stress showed enhanced transcript levels of the genes encoding the high Affinity Potassium Transporter 1 (HKT1) and the inward-rectifying K+ channels KAT1 and KAT2, which play key roles in regulating Na+ and K+ homeostasis. The effect of P. indica colonization on AtHKT1;1 expression was also confirmed in the Arabidopsis line gl1-HKT:AtHKT1;1 that expresses an additional AtHKT1;1 copy driven by the native promoter. Colonization of the gl1-HKT:AtHKT1;1 by P. indica also increased lateral roots density and led to a better Na+/K+ ratio, which may be attributed to the observed increase in KAT1 and KAT2 transcript levels. Our findings demonstrate that P. indica colonization promotes Arabidopsis growth under salt stress conditions and that this effect is likely caused by modulation of the expression levels of the major Na+ and K+ ion channels, which allows establishing a balanced ion homeostasis of Na+/K+ under salt stress conditions.

  4. Gene Profiling of Aortic Valve Interstitial Cells under Elevated Pressure Conditions: Modulation of Inflammatory Gene Networks

    Directory of Open Access Journals (Sweden)

    James N. Warnock

    2011-01-01

    Full Text Available The study aimed to identify mechanosensitive pathways and gene networks that are stimulated by elevated cyclic pressure in aortic valve interstitial cells (VICs and lead to detrimental tissue remodeling and/or pathogenesis. Porcine aortic valve leaflets were exposed to cyclic pressures of 80 or 120 mmHg, corresponding to diastolic transvalvular pressure in normal and hypertensive conditions, respectively. Linear, two-cycle amplification of total RNA, followed by microarray was performed for transcriptome analysis (with qRT-PCR validation. A combination of systems biology modeling and pathway analysis identified novel genes and molecular mechanisms underlying the biological response of VICs to elevated pressure. 56 gene transcripts related to inflammatory response mechanisms were differentially expressed. TNF-α, IL-1α, and IL-1β were key cytokines identified from the gene network model. Also of interest was the discovery that pentraxin 3 (PTX3 was significantly upregulated under elevated pressure conditions (41-fold change. In conclusion, a gene network model showing differentially expressed inflammatory genes and their interactions in VICs exposed to elevated pressure has been developed. This system overview has detected key molecules that could be targeted for pharmacotherapy of aortic stenosis in hypertensive patients.

  5. Weak Nonlinear Double-Diffusive Magnetoconvection in a Newtonian Liquid under Temperature Modulation

    Directory of Open Access Journals (Sweden)

    B. S. Bhadauria

    2014-01-01

    Full Text Available The present paper deals with a weak nonlinear theory of double-diffusive magnetoconvection in an electrically conducting Newtonian liquid, confined between two horizontal surfaces, under a constant vertical magnetic field, and subjected to imposed time-periodic thermal boundaries. The temperature of both walls is varied time periodic in this case. The disturbances are expanded in terms of power series of amplitude of convection, which is assumed to be small. Using nonautonomous Ginzburg-Landau equation, the Nusselt and Sherwood numbers obtained analytically and studied heat and mass transport in the system. Effect of various parameters on the heat and mass transport is discussed extensively. It is found that the effect of magnetic field is to stabilize the system. Further, it is also notified that the heat and mass transport can be controlled by suitably adjusting the external parameters of the system.

  6. Modulation of MicroRNAs by Phytochemicals in Cancer: Underlying Mechanisms and Translational Significance

    Science.gov (United States)

    Srivastava, Sanjeev K.; Arora, Sumit; Averett, Courey; Singh, Ajay P.

    2015-01-01

    MicroRNAs (miRNAs) are small, endogenous noncoding RNAs that regulate a variety of biological processes such as differentiation, development, and survival. Recent studies suggest that miRNAs are dysregulated in cancer and play critical roles in cancer initiation, progression, and chemoresistance. Therefore, exploitation of miRNAs as targets for cancer prevention and therapy could be a promising approach. Extensive evidence suggests that many naturally occurring phytochemicals regulate the expression of numerous miRNAs involved in the pathobiology of cancer. Therefore, an understanding of the regulation of miRNAs by phytochemicals in cancer, their underlying molecular mechanisms, and functional consequences on tumor pathophysiology may be useful in formulating novel strategies to combat this devastating disease. These aspects are discussed in this review paper with an objective of highlighting the significance of these observations from the translational standpoint. PMID:25853141

  7. Comparison of Predictive Models for Photovoltaic Module Performance under Sudanese-Sahelian Climate

    Directory of Open Access Journals (Sweden)

    Njomo Donatien

    2012-06-01

    Full Text Available This paper investigates various approaches to the modeling of photovoltaic systems and tests their accuracy under tropical climate. Particularly the single diode model is used to estimate the electrical behavior of the cell with respect changes on environmental parameter of temperature and irradiance. A particular typical MXS60 solar panel is used for models evaluation and results are comparing with points taken directly from the experience made on the same panel in tropical climate of the Sudan type . The accuracy of models was computed and the better model was determined for local conditions. The analysis of the curves shows that the single diode model has the better accuracy whereas the Photovoltaic geographical information system (PVGIS approach seems to be not appropriate for the region.

  8. Operant conditioning of enhanced pain sensitivity by heat-pain titration.

    Science.gov (United States)

    Becker, Susanne; Kleinböhl, Dieter; Klossika, Iris; Hölzl, Rupert

    2008-11-15

    Operant conditioning mechanisms have been demonstrated to be important in the development of chronic pain. Most experimental studies have investigated the operant modulation of verbal pain reports with extrinsic reinforcement, such as verbal reinforcement. Whether this reflects actual changes in the subjective experience of the nociceptive stimulus remained unclear. This study replicates and extends our previous demonstration that enhanced pain sensitivity to prolonged heat-pain stimulation could be learned in healthy participants through intrinsic reinforcement (contingent changes in nociceptive input) independent of verbal pain reports. In addition, we examine whether different magnitudes of reinforcement differentially enhance pain sensitivity using an operant heat-pain titration paradigm. It is based on the previously developed non-verbal behavioral discrimination task for the assessment of sensitization, which uses discriminative down- or up-regulation of stimulus temperatures in response to changes in subjective intensity. In operant heat-pain titration, this discriminative behavior and not verbal pain report was contingently reinforced or punished by acute decreases or increases in heat-pain intensity. The magnitude of reinforcement was varied between three groups: low (N1=13), medium (N2=11) and high reinforcement (N3=12). Continuous reinforcement was applied to acquire and train the operant behavior, followed by partial reinforcement to analyze the underlying learning mechanisms. Results demonstrated that sensitization to prolonged heat-pain stimulation was enhanced by operant learning within 1h. The extent of sensitization was directly dependent on the received magnitude of reinforcement. Thus, operant learning mechanisms based on intrinsic reinforcement may provide an explanation for the gradual development of sustained hypersensitivity during pain that is becoming chronic.

  9. Pain-related mood influences pain perception differently in fibromyalgia and multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Borg C

    2014-01-01

    Full Text Available Céline Borg,1–3 Catherine Padovan,4,5 Catherine Thomas-Antérion,1,2 Céline Chanial,1 Anaïs Sanchez,1,5 Marion Godot,6 Roland Peyron,1,6,7 Odile De Parisot,5 Bernard Laurent1,6,71Neurology/Neuropsychology, Center Memory of Resources and Research Unit, North Saint-Etienne University Hospital Center, Avenue Albert Raimond, Saint-Priest-en-Jarez, France; 2Study of Cognitive Mechansims Laboratory, 3Psychology Unit, University Lumière of Lyon 2, Bron, France; 4Brain Dynamics and Cognition, Lyon Neuroscience Research Center and Vinatier Hospital Center, Bron, France; 5Germaine Revel Center, Dargoire, France; 6Pain Center, North Saint-Etienne University Hospital Center, Saint-Priest-en-Jarez, France; 7Central Integration of Pain, Lyon Neuroscience Research Center, Bron, FranceAbstract: In patients, the perception of pain intensity may be influenced by the subjective representation of their disease. Although both multiple sclerosis (MS and fibromyalgia (FM possibly include chronic pain, they seem to elicit different disease representations because of the difference in their respective etiology, the former presenting evidence of underlying lesions as opposed to the latter. Thus, we investigated whether patients with FM differed from patients with MS with respect to their perception of “own” pain as well as others' pain. In addition, the psychological concomitant factors associated with chronic pain were considered. Chronic pain patients with FM (n=13 or with MS (n=13 participated in this study. To assess specific pain-related features, they were contrasted with 12 other patients with MS but without chronic pain and 31 controls. A questionnaire describing imaginary painful situations showed that FM patients rated situations applied to themselves as less painful than did the controls. Additionally, pain intensity attributed to facial expressions was estimated as more intense in FM compared with the other groups of participants. There is good

  10. ADX71943 and ADX71441, novel positive allosteric modulators of the GABABreceptor with distinct central/peripheral profiles, show efficacy in the monosodium iodoacetate model of chronic osteoarthritis pain in the rat.

    Science.gov (United States)

    Kalinichev, Mikhail; Donovan-Rodriguez, Tansy; Girard, Françoise; Haddouk, Hasnaá; Royer-Urios, Isabelle; Schneider, Manfred; Bate, Simon T; Marker, Cheryl; Pomonis, James D; Poli, Sonia

    2017-01-15

    We tested novel positive allosteric modulators (PAMs) of the γ-aminobutyric acid receptor B (GABA B ), ADX71943 and ADX71441in the monosodium iodoacetate model of chronic osteoarthritis pain in rats with the objective to delineate the role of peripheral versus central GABA B receptor populations in modulation of chronic pain. Anesthetized Sprague-Dawley rats received an injection of monosodium iodoacetate into the knee and were tested for hyperalgesia starting post-MIA day 14. Effects of compounds on ipsilateral joint compression threshold were evaluated on post-MIA day 14 (after acute treatment), as well as after repeated, daily treatment on days 21 and 28 (ADX71943 only) and were compared to those of celecoxib (30mg/kg, p.o.). The PAMs were also tested in the rat rotarod test for potential muscle-relaxant effects. Acutely, ADX71943 (1-30mg/kg, p.o.), the peripherally restricted PAM, resulted in similar increases in pain threshold across the doses on day 14, while showing reduced efficacy on day 21 and no efficacy on day 28. A clear reduction in the efficacy of celecoxib across testing was also noted in this experiment. Acutely ADX71441 (0.3-15mg/kg, p.o.), the central-peripheral PAM, resulted in over 2-fold increases in pain threshold at 15mg/kg (but not at lower doses) on day 14, while causing more modest effects on day 21. Celecoxib increased pain threshold after both acute and daily treatment, showing overall similar efficacy. Thus, early, presumably more inflammatory phase of osteoarthritis pain in more sensitive to GABA B PAMs with peripherally restricted profile, while later, presumably more neuropathic phase is more sensitive to PAMs with central-peripheral profile. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Tight-binding electrons on triangular and kagome lattices under staggered modulated magnetic fields: quantum Hall effects and Hofstadter butterflies

    Energy Technology Data Exchange (ETDEWEB)

    Li Juan; Wang Yifei; Gong Changde, E-mail: yfwang_nju@hotmail.com [Center for Statistical and Theoretical Condensed Matter Physics, and Department of Physics, Zhejiang Normal University, Jinhua 321004 (China)

    2011-04-20

    We consider the tight-binding models of electrons on a two-dimensional triangular lattice and kagome lattice under staggered modulated magnetic fields. Such fields have two components: a uniform-flux part with strength {phi}, and a staggered-flux part with strength {Delta}{phi}. Various properties of the Hall conductances and Hofstadter butterflies are studied. When {phi} is fixed, variation of {Delta}{phi} leads to the quantum Hall transitions and Chern numbers of Landau subbands being redistributed between neighboring pairs. The energy spectra with nonzero {Delta}{phi}s have similar fractal structures but quite different energy gaps compared with the original Hofstadter butterflies of {Delta}{phi} = 0. Moreover, the fan-like structure of Landau levels in the low magnetic field region is also modified appreciably by {Delta}{phi}.

  12. Voltage-Balancing Method for Modular Multilevel Converters Under Phase-Shifted Carrier-Based Pulsewidth Modulation

    DEFF Research Database (Denmark)

    Deng, Fujin; Chen, Zhe

    2015-01-01

    The modular multilevel converter (MMC) becomes attractive for medium- or high-power applications because of the advantages of high modularity, availability, and power quality. One of the technical challenges associated with an MMC is the balancing of the capacitors' voltages. In this paper......, a voltage-balancing control method is proposed for the MMC under phase-shifted carrier-based pulsewidth modulation. The proposed voltage-balancing method uses the linearization method for pulse sorting without arm current measurement, which can control the capacitor charge transfer to balance the capacitor....../EMTDC are conducted, and a downscale MMC prototype is also tested with the proposed method. The study results show the effectiveness of the proposed voltage-balancing method....

  13. Characteristic Analysis and Fault-Tolerant Control of Circulating Current for Modular Multilevel Converters under Sub-Module Faults

    Directory of Open Access Journals (Sweden)

    Wen Wu

    2017-11-01

    Full Text Available A modular multilevel converter (MMC is considered to be a promising topology for medium- or high-power applications. However, a significantly increased amount of sub-modules (SMs in each arm also increase the risk of failures. Focusing on the fault-tolerant operation issue for the MMC under SM faults, the operation characteristics of MMC with different numbers of faulty SMs in the arms are analyzed and summarized in this paper. Based on the characteristics, a novel circulating current-suppressing (CCS fault-tolerant control strategy comprised of a basic control unit (BCU and virtual resistance compensation control unit (VRCCU in two parts is proposed, which has three main features: (i it can suppress the multi-different frequency components of the circulating current under different SM fault types simultaneously; (ii it can help fast limiting of the transient fault current caused at the faulty SM bypassed moment; and (iii it does not need extra communication systems to acquire the information of the number of faulty SMs. Moreover, by analyzing the stability performance of the proposed controller using the Root-Locus criterion, the election principle of the value of virtual resistance is revealed. Finally, the efficiency of the control strategy is confirmed with the simulation and experiment studies under different fault conditions.

  14. [Correlation between dental pulp demyelination degree and pain visual analogue scale scores data under acute and chronic pulpitis].

    Science.gov (United States)

    Korsantiia, N B; Davarashvili, X T; Gogiashvili, L E; Mamaladze, M T; Tsagareli, Z G; Melikadze, E B

    2013-05-01

    The aim of study is the analysis of pulp nerve fibers demyelination degree and its relationship with Visual Analogue Scale (VAS) score that may be measured as objective criteria. Material and methods of study. Step I: electron micrografs of dental pulp simples with special interest of myelin structural changes detected in 3 scores system, obtained from 80 patients, displays in 4 groups: 1) acute and 2) chronic pulpitis without and with accompined systemic deseases, 20 patients in each group. Dental care was realized in Kutaisi N1 Dental clinic. Step II - self-reported VAS used for describing dental pain. All data were performed by SPSS 10,0 version statistics including Spearmen-rank and Mann-Whitny coefficients for examine the validity between pulp demyelination degree and pain intensity in verbal, numbered and box scales. Researched Data were shown that damaged myelin as focal decomposition of membranes and Schwann cells hyperthrophia correspond with acute dental pain intensity as Spearman index reported in VAS numbered Scales, myelin and axoplasm degeneration as part of chronic gangrenous pulpitis disorders are in direct correlation with VAS in verbal, numbered and behavioral Rating Scales. In fact, all morphological and subjective data, including psychomotoric assessment of dental painin pulpitis may be used in dental practice for evaluation of pain syndrome considered personal story.

  15. Auxin modulates the enhanced development of root hairs in Arabidopsis thaliana (L.) Heynh. under elevated CO(2).

    Science.gov (United States)

    Niu, Yaofang; Jin, Chongwei; Jin, Gulei; Zhou, Qingyan; Lin, Xianyong; Tang, Caixian; Zhang, Yongsong

    2011-08-01

    Root hairs may play a critical role in nutrient acquisition of plants grown under elevated CO(2) . This study investigated how elevated CO(2) enhanced the development of root hairs in Arabidopsis thaliana (L.) Heynh. The plants under elevated CO(2) (800 µL L(-1)) had denser and longer root hairs, and more H-positioned cells in root epidermis than those under ambient CO(2) (350 µL L(-1)). The elevated CO(2) increased auxin production in roots. Under elevated CO(2) , application of either 1-naphthoxyacetic acid (1-NOA) or N-1-naphthylphthalamic acid (NPA) blocked the enhanced development of root hairs. The opposite was true when the plants under ambient CO(2) were treated with 1-naphthylacetic acid (NAA), an auxin analogue. Furthermore, the elevated CO(2) did not enhance the development of root hairs in auxin-response mutants, axr1-3, and auxin-transporter mutants, axr4-1, aux1-7 and pin1-1. Both elevated CO(2) and NAA application increased expressions of caprice, triptychon and rho-related protein from plants 2, and decreased expressions of werewolf, GLABRA2, GLABRA3 and the transparent testa glabra 1, genes related to root-hair development, while 1-NOA and NPA application had an opposite effect. Our study suggests that elevated CO(2) enhanced the development of root hairs in Arabidopsis via the well-characterized auxin signalling and transport that modulate the initiation of root hairs and the expression of its specific genes. © 2011 Blackwell Publishing Ltd.

  16. CO2 -dependent metabolic modulation in red blood cells stored under anaerobic conditions.

    Science.gov (United States)

    Dumont, Larry J; D'Alessandro, Angelo; Szczepiorkowski, Zbigniew M; Yoshida, Tatsuro

    2016-02-01

    Anaerobic red blood cell (RBC) storage reduces oxidative damage, maintains adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (DPG) levels, and has superior 24-hour recovery at 6 weeks compared to standard storage. This study will determine if removal of CO2 during O2 depletion by gas exchange may affect RBCs during anaerobic storage. This is a matched three-arm study (n = 14): control, O2 and CO2 depleted with Ar (AN), and O2 depleted with 95%Ar/5%CO2 (AN[CO2 ]). RBCs in additives AS-3 or OFAS-3 were evenly divided into three bags, and anaerobic conditions were established by gas exchange. Bags were stored at 1 to 6°C in closed chambers under anaerobic conditions or ambient air, sampled weekly for up to 9 weeks for a panel of in vitro tests. A full metabolomics screening was conducted for the first 4 weeks of storage. Purging with Ar (AN) results in alkalization of the RBC and increased glucose consumption. The addition of 5% CO2 to the purging gas prevented CO2 loss with an equivalent starting and final pH and lactate to control bags (p > 0.5, Days 0-21). ATP levels are higher in AN[CO2 ] (p CO2 ] arms (p = 0.6). Maintenance of ATP in the AN[CO2 ] arm demonstrates that ATP production is not solely a function of the pH effect on glycolysis. CO2 in anaerobic storage prevented the maintenance of DPG, and DPG production appears to be pH dependent. CO2 as well as O2 depletion provides metabolic advantage for stored RBCs. © 2015 AABB.

  17. TrpA1 activation in peripheral sensory neurons underlies the ionic basis of pain hypersensitivity in response to vinca alkaloids.

    Directory of Open Access Journals (Sweden)

    Nina Boiko

    Full Text Available Chemotherapy induced peripheral neuropathy (CIPN, a side effect of many anti-cancer drugs including the vinca alkaloids, is characterized by a severe pain syndrome that compromises treatment in many patients. Currently there are no effective treatments for this pain syndrome except for the reduction of anti-cancer drug dose. Existing data supports the model that the pain associated with CIPN is the result of anti-cancer drugs augmenting the function of the peripheral sensory nociceptors but the cellular mechanisms underlying the effects of anti-cancer drugs on sensory neuron function are not well described. Studies from animal models have suggested a number of disease etiologies including mitotoxicity, axonal degeneration, immune signaling, and reduced sensory innervations but these outcomes are the result of prolonged treatment paradigms and do not necessarily represent the early formative events associated with CIPN. Here we show that acute exposure to vinca alkaloids results in an immediate pain syndrome in both flies and mice. Furthermore, we demonstrate that exposure of isolated sensory neurons to vinca alkaloids results in the generation of an inward sodium current capable of depolarizing these neurons to threshold resulting in neuronal firing. These neuronal effects of vinca alkaloids require the transient receptor potential ankyrin-1 (TrpA1 channel, and the hypersensitization to painful stimuli in response to the acute exposure to vinca alkaloids is reduced in TrpA1 mutant flies and mice. These findings demonstrate the direct excitation of sensory neurons by CIPN-causing chemotherapy drugs, and identify TrpA1 as an important target during the pathogenesis of CIPN.

  18. Psychological aspects of pain.

    Science.gov (United States)

    Gorczyca, Rafał; Filip, Rafał; Walczak, Ewa

    2013-01-01

    functional magnetic resonance imaging (fMRI) was used showed that pain catastrophizing, independent of the influence of depression, was significantly associated with increased activity in brain areas related to anticipation of pain, attention to pain, emotional aspects of pain and motor control. Pain behaviour is a conditioned pain. Care and concern on the part of others, secondarily enhance a patient's pain behaviours, which lead to an increase in the intensity of the pain experienced. A history of early life adversity (ELA) - rejection, neglect, physical or sexual abuse is related to the development of irritable bowel syndrome (IBS) in adulthood. Ovarian hormones have been shown to modulate pain sensitivity. IMAGING OF THE HUMAN BRAIN IN CHRONIC PAIN: Acute pain and chronic pain are encoded in different regions of the brain. Chronic pain can be considered a driving force that carves cortical anatomy and physiology, creating the chronic pain brain/ mind state. Cognitive-behavioural methods of pain treatment in domains of pain experience, cognitive coping and appraisal (positive coping measures), and reduced pain experience are effective in reducing pain in patients.

  19. Physical therapy under hypnosis for the treatment of patients with type 1 complex regional pain syndrome of the hand and wrist: Retrospective study of 20 cases.

    Science.gov (United States)

    Lebon, J; Rongières, M; Apredoaei, C; Delclaux, S; Mansat, P

    2017-06-01

    Type 1 complex regional painful syndrome (CRPS-1) has a complex physiopathology. The aim of this study was to evaluate the effectiveness of physical therapy under hypnotherapy to treat this condition. Twenty patients with CRPS-1 at the wrist and hand were evaluated retrospectively: 13 women and 7 men with an average age of 56 years (34-75). Thirteen patients were in the inflammatory phase and 7 in the dystrophic phase. The main endpoints were pain (VAS, analgesic use), stiffness (wrist and finger range of motion), and strength (pinch and grasp). Secondary endpoints were functional scores (QuickDASH, PWRE), patient satisfaction, return to work, and side effects. Results were satisfactory in all cases after 5.4 sessions on average. VAS decreased by 4 points, PWRE-pain by 4.1 points, and analgesic use was limited to paracetamol upon request. Finger and wrist range of motion increased and the QuickDASH decreased by 34 points, PRWE-function by 3.8 points, pinch strength increased 4 points, and grasp strength by 10 points. Return to work was possible in 80% of the cases. All patients were satisfied or very satisfied with the treatment. Physical therapy under hypnosis appears to be an effective treatment for CRPS-1 at the wrist and hand no matter the etiology. Copyright © 2017 SFCM. Published by Elsevier Masson SAS. All rights reserved.

  20. Use of a multimedia module to aid the informed consent process in patients undergoing gynecologic laparoscopy for pelvic pain: randomized controlled trial.

    Science.gov (United States)

    Ellett, Lenore; Villegas, Rocio; Beischer, Andrew; Ong, Nicole; Maher, Peter

    2014-01-01

    To determine whether providing additional information to the standard consent process, in the form of a multimedia module (MM), improves patient knowledge about operative laparoscopy without increasing anxiety. Randomized controlled trial (Canadian Task Force classification I). Two outpatient gynecologic clinics, one in a private hospital and the other in a public teaching hospital. Forty-one women aged 19 to 51 years (median, 35.6 years) requiring operative laparoscopy for investigation and treatment of pelvic pain. Following the standard informed consent process, patients were randomized to watch the MM (intervention group, n = 21) or not (control group, n = 20). The surgeon was blinded to the group assignments. All patients completed a knowledge questionnaire and the Spielberger short-form State-Trait Anxiety Inventory. Six weeks after recruitment, patients completed the knowledge questionnaire and the State-Trait Anxiety Inventory a second time to assess knowledge retention and anxiety scores. Patient knowledge of operative laparoscopy, anxiety level, and acceptance of the MM were recorded. The MM intervention group demonstrated superior knowledge scores. Mean (SE) score in the MM group was 11.3 (0.49), and in the control group was 7.9 (0.50) (p <.001) (maximum score, 14). This did not translate into improved knowledge scores 6 weeks later; the score in the MM group was 8.4 (0.53) vs. 7.8 (0.50) in the control group (p = .44). There was no difference in anxiety levels between the groups at intervention or after 6 weeks. Overall, patients found the MM acceptable, and 18 women (86%) in the intervention group and 12 (60%) in the control group stated they would prefer this style of informed consent in the future. Use of an MM enhances the informed consent process by improving patient knowledge, in the short term, without increasing anxiety. Copyright © 2014 AAGL. Published by Elsevier Inc. All rights reserved.

  1. Methadone for Cancer Pain

    Directory of Open Access Journals (Sweden)

    Eric E. Prommer

    2010-07-01

    Full Text Available Pain is one of the most common and incapacitating symptoms experienced by patients with advanced cancer. Methadone is a potent opioid with strong affinity for the µ opioid receptor. In addition to being a potent µ opioid receptor ligand, methadone blocks the N-methyl-D-aspartic acid receptor and modulates neurotransmitters involved in descending pain modulation. These 3 properties enhance analgesic activity. Methadone’s lack of active metabolites makes it an attractive option when opioid responsiveness declines and renal insufficiency complicates opioid therapy. A lipophilic opioid, methadone can be given by multiple routes. Clinical trial data show equivalence with morphine as an analgesic in moderate to severe cancer pain. Further investigations are needed to define the role of methadone in the management of breakthrough pain and neuropathic pain and to determine whether it is truly superior to morphine, the gold standard of cancer analgesia.

  2. Coping Styles, Pain Expressiveness, and Implicit Theories of Chronic Pain.

    Science.gov (United States)

    Higgins, N C; Bailey, S Jeffrey; LaChapelle, Diane L; Harman, Katherine; Hadjistavropoulos, Thomas

    2015-01-01

    Whereas some individuals use active coping strategies and are able to adaptively cope with their pain, others use passive strategies and catastrophic appraisals, which are often associated with increased displays of pain behavior and negative pain-related outcomes. To investigate attribution-based implicit theories as a potential underlying mechanism that might affect coping success, we hypothesized that pain patients with an incremental implicit theory of pain (i.e., view pain as malleable) would have more active coping strategies, lower levels of pain expressiveness, and better pain-related outcomes than those with an entity implicit theory of pain (i.e., view pain as nonmalleable). Patients with chronic back pain undergoing a functional assessment completed a variety of self-report measures and participated in a pain-inducing physiotherapy procedure. The results revealed those with an incremental theory of pain used more active coping strategies, displayed less pain behavior, and reported better pain-related outcomes (e.g., lower levels of depression) than individuals with an entity theory of pain. The findings suggest implicit theories of pain may represent an underlying social-cognitive mechanism linked to important coping, emotional, and expressive reactions to chronic pain. Identifying such a mechanism may provide valuable information for the assessment and treatment of chronic pain.

  3. Pain-relevant anxiety affects desire for pain relief, but not pain perception

    Directory of Open Access Journals (Sweden)

    Adriana Banozic

    2017-01-01

    Full Text Available Background: Pain context plays a significant role in the perception of pain. Despite recent interest in vicarious learning and anxiety in pain modulation, there have been no attempts to explore pain modulation by specific environmental cues. Aims: Therefore, the present study evaluated pain responses in the condition that was attributed as either anxiety relevant (AR or anxiety irrelevant. Materials and Methods: Participants were exposed to both conditions through social observational learning. Pain perception was assessed by means of a visual analog scale ranging from 0 = no pain to 10 = maximum imaginable pain. State anxiety, empathy, expectancy, and desire for pain relief were also measured at both neutral and emotionally inducing conditions. Results: No effect of relevancy of anxiety for the pain context on any of the pain-related constructs was found. However, participants in the AR condition reported an increased desire for pain relief. Maximizing similarities between observed and experienced pain context did not enhance observational learning effects in the emotionally inducing condition regardless of its relevance, but significant changes were found in comparison to the affectively neutral group. Conclusions: These results could have potentially significant clinical implications suggesting that even though observing painful procedures does not increase pain it could affect medication usage.

  4. Shaped magnetic field pulses by multi-coil repetitive transcranial magnetic stimulation (rTMS) differentially modulate anterior cingulate cortex responses and pain in volunteers and fibromyalgia patients

    Science.gov (United States)

    2013-01-01

    Background Repetitive transcranial magnetic stimulation (rTMS) has shown promise in the alleviation of acute and chronic pain by altering the activity of cortical areas involved in pain sensation. However, current single-coil rTMS technology only allows for effects in surface cortical structures. The ability to affect activity in certain deep brain structures may however, allow for a better efficacy, safety, and tolerability. This study used PET imaging to determine whether a novel multi-coil rTMS would allow for preferential targeting of the dorsal anterior cingulate cortex (dACC), an area always activated with pain, and to provide preliminary evidence as to whether this targeted approach would allow for efficacious, safe, and tolerable analgesia both in a volunteer/acute pain model as well as in fibromyalgia chronic pain patients. Methods Part 1: Different coil configurations were tested in a placebo-controlled crossover design in volunteers (N = 16). Tonic pain was induced using a capsaicin/thermal pain model and functional brain imaging was performed by means of H215O positron emission tomography – computed tomography (PET/CT) scans. Differences in NRS pain ratings between TMS and sham treatment (NRSTMS-NRSplacebo) which were recorded each minute during the 10 minute PET scans. Part 2: 16 fibromyalgia patients were subjected to 20 multi-coil rTMS treatments over 4 weeks and effects on standard pain scales (Brief Pain Inventory, item 5, i.e. average pain NRS over the last 24 hours) were recorded. Results A single 30 minute session using one of 3 tested rTMS coil configurations operated at 1 Hz consistently produced robust reduction (mean 70% on NRS scale) in evoked pain in volunteers. In fibromyalgia patients, the 20 rTMS sessions also produced a significant pain inhibition (43% reduction in NRS pain over last 24 hours), but only when operated at 10 Hz. This degree of pain control was maintained for at least 4 weeks after the final session

  5. Modulation of Protein Quality Control Systems as Novel Mechanisms Underlying Functionality of Food Phytochemicals

    Directory of Open Access Journals (Sweden)

    Kohta Ohnishi

    2013-10-01

    phytochemicals, such as curcumin, phenethyl isothiocyanate, ursolic acid, and lycopene, were significantly active, whereas most nutrients were virtually inactive. These results may be associated with the fact that phytochemicals, but not nutrients, are foreign chemicals to animals, as noted above.Functional Foods in Health and Disease 2013; 3(10:400-415 Page 402 of 415 Conclusion: Up-regulation of antioxidant and xenobiotics-metabolizing enzymes has been reported to be an adaptive response in animals exposed to phytochemicals. Our present results imply that the process also increases the capacity to counteract proteo-stresses through activation of PQC systems. This putative phenomenon, representing the concept of hormesis[5], may be associated with mechanisms underlying the physiological functions of phytochemicals. Therefore, chronic ingestion of this class of chemicals may result in ‘chemical training’, in which self-defense systems are continuously activated for adaptation to phytochemical-driven stresses.

  6. A Novel Identification Method of Thermal Resistances of Thermoelectric Modules Combining Electrical Characterization Under Constant Temperature and Heat Flow Conditions

    Directory of Open Access Journals (Sweden)

    Saima Siouane

    2016-11-01

    Full Text Available The efficiency of a Thermoelectric Module (TEM is not only influenced by the material properties, but also by the heat losses due to the internal and contact thermal resistances. In the literature, the material properties are mostly discussed, mainly to increase the well-known thermoelectric figure of merit ZT. Nevertheless, when a TEM is considered, the separate characterization of the materials of the p and n elements is not enough to have a suitable TEM electrical model and evaluate more precisely its efficiency. Only a few recent papers deal with thermal resistances and their influence on the TEM efficiency; mostly, the minimization of these resistances is recommended, without giving a way to determine their values. The aim of the present paper is to identify the internal and contact thermal resistances of a TEM by electrical characterization. Depending on the applications, the TEM can be used either under constant temperature gradient or constant heat flow conditions. The proposed identification approach is based on the theoretical electrical modeling of the TEM, in both conditions. It is simple to implement, because it is based only on open circuit test conditions. A single electrical measurement under both conditions (constant-temperature and constant-heat is needed. Based on the theoretical electrical models, one can identify the internal and thermal resistances.

  7. Response Analysis on Electrical Pulses under Severe Nuclear Accident Temperature Conditions Using an Abnormal Signal Simulation Analysis Module

    Directory of Open Access Journals (Sweden)

    Kil-Mo Koo

    2012-01-01

    Full Text Available Unlike design basis accidents, some inherent uncertainties of the reliability of instrumentations are expected while subjected to harsh environments (e.g., high temperature and pressure, high humidity, and high radioactivity occurring in severe nuclear accident conditions. Even under such conditions, an electrical signal should be within its expected range so that some mitigating actions can be taken based on the signal in the control room. For example, an industrial process control standard requires that the normal signal level for pressure, flow, and resistance temperature detector sensors be in the range of 4~20 mA for most instruments. Whereas, in the case that an abnormal signal is expected from an instrument, such a signal should be refined through a signal validation process so that the refined signal could be available in the control room. For some abnormal signals expected under severe accident conditions, to date, diagnostics and response analysis have been evaluated with an equivalent circuit model of real instruments, which is regarded as the best method. The main objective of this paper is to introduce a program designed to implement a diagnostic and response analysis for equivalent circuit modeling. The program links signal analysis tool code to abnormal signal simulation engine code not only as a one body order system, but also as a part of functions of a PC-based ASSA (abnormal signal simulation analysis module developed to obtain a varying range of the R-C circuit elements in high temperature conditions. As a result, a special function for abnormal pulse signal patterns can be obtained through the program, which in turn makes it possible to analyze the abnormal output pulse signals through a response characteristic of a 4~20 mA circuit model and a range of the elements changing with temperature under an accident condition.

  8. Peripheral changes in endometriosis-associated pain

    Science.gov (United States)

    Morotti, Matteo; Vincent, Katy; Brawn, Jennifer; Zondervan, Krina T.; Becker, Christian M.

    2014-01-01

    BACKGROUND Pain remains the cardinal symptom of endometriosis. However, to date, the underlying mechanisms are still only poorly understood. Increasing evidence points towards a close interaction between peripheral nerves, the peritoneal environment and the central nervous system in pain generation and processing. Recently, studies demonstrating nerve fibres and neurotrophic and angiogenic factors in endometriotic lesions and their vicinity have led to increased interest in peripheral changes in endometriosis-associated pain. This review focuses on the origin and function of these nerves and factors as well as possible peripheral mechanisms that may contribute to the generation and modulation of pain in women with endometriosis. METHODS We conducted a systematic search using several databases (PubMed, MEDLINE, EMBASE and CINAHL) of publications from January 1977 to October 2013 to evaluate the possible roles of the peripheral nervous system in endometriosis pathophysiology and how it can contribute to endometriosis-associated pain. RESULTS Endometriotic lesions and peritoneal fluid from women with endometriosis had pronounced neuroangiogenic properties with increased expression of new nerve fibres, a shift in the distribution of sensory and autonomic fibres in some locations, and up-regulation of several neurotrophins. In women suffering from deep infiltrating endometriosis and bowel endometriosis, in which the anatomical distribution of lesions is generally more closely related to pelvic pain symptoms, endometriotic lesions and surrounding tissues present higher nerve fibre densities compared to peritoneal lesions and endometriomas. More data are needed to fully confirm a direct correlation between fibre density in these locations and the amount of perceived pain. A better correlation between the presence of nerve fibres and pain symptoms seems to exist for eutopic endometrium. However, this appears not to be exclusive to endometriosis. No correlation between

  9. Past Pain Experience and Experimentally induced Pain Perception.

    Science.gov (United States)

    Paquet, Aude; Plansont, Brigitte; Labrunie, Anaïs; Malauzat, Dominique; Girard, Murielle

    2017-12-01

    Many intercurrent factors may be involved in the modulation of the pain message and its expression, such as the previous experience of pain built along the life. In this study, we aimed to determine whether susceptibility to experimentally induced pain is differentially influenced by the individual previous painful experience in subjects with schizophrenia (SC) major depression (MD), and controls (C). The SC (30), MD (32) and C (30) groups participated in experimental pain tests (application of pressure and induction of ischemia) after a semi-structured interview to make an inventory of the previous painful experiences, and the evaluation of anxiety either with autonomic (heart rate, blood pressure) or psychological (Hospital Anxiety Depression scale HAD) measures, and catastrophism. The reported pain intensities, severities, duration, of the previous pain events, and the number of previous painful events were equivalent in the three groups, except for the number of painful events experimented before the last six months which was lower in the MD group. Experimental pain sensitivity was influenced by the diagnosis, the HAD scores or the number and intensities of previous lived painful events. The lack of a past experience of pain was comparable for the different groups, suggesting that psychiatric disorders do not affect the experience of pain associated with daily life or past events. For each subject, the reported previous experience of pain influences the present feeling of pain.

  10. Ephrins and pain.

    Science.gov (United States)

    Vasileiou, Ioanna; Adamakis, Ioannis; Patsouris, Efstratios; Theocharis, Stamatios

    2013-08-01

    The ephrin receptor family is the largest family of receptor tyrosine kinases, which comprises 14 members that are divided into A and B subclasses. The ephrin receptor (Eph-receptor) ligands are named ephrins. Ephrins/Eph receptors interact with a variety of membrane receptors that respond to chemokines, neurotransmitters or growth factors. A growing body of evidence indicates that ephrins/Eph receptors are involved in the modulation of different types of pain. A literature review summarizing the most recent data in terms of ephrins and their ligands and their association with different types of pain. Moreover, the latest knowledge regarding the involvement of ephrins/Eph receptors in pain modulation as well as its possible therapeutic perspectives are presented. The ephrins/Eph receptors system seems to be an emerging target for pain drug discovery, because it is involved in the pathophysiology of many types of pain. The modulation of different types of pain by selective agonists or antagonists may hold tremendous therapeutic potential in various pain conditions mentioned in this review. However, the current limited but promising data, merit consideration and further investigation.

  11. 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.

  12. 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. ...

  13. Heel pain

    Science.gov (United States)

    Pain - heel ... Heel pain is most often the result of overuse. However, it may be caused by an injury. Your heel ... on the heel Conditions that may cause heel pain include: Swelling and pain in the Achilles tendon ...

  14. Flank pain

    Science.gov (United States)

    Pain - side; Side pain ... Flank pain can be a sign of a kidney problem. But, since many organs are in this area, other causes are possible. If you have flank pain and fever , chills, blood in the urine, or ...

  15. Pain evaluation in dairy cattle

    DEFF Research Database (Denmark)

    Gleerup, Karina Charlotte Bech; Andersen, Pia Haubro; Munksgaard, Lene

    2015-01-01

    Pain compromises the welfare of animals. A prerequisite for being able to alleviate pain is that we are able to recognize it. Potential behavioural signs of pain were investigated for dairy cattle with the aim of constructing a pain scale for use under production conditions. Forty-three cows were......, piloerection, was also significant but seemed difficult to use as it changed rapidly; p 

  16. Clear signals or mixed messages: inter-individual emotion congruency modulates brain activity underlying affective body perception

    Science.gov (United States)

    de Gelder, B.

    2016-01-01

    The neural basis of emotion perception has mostly been investigated with single face or body stimuli. However, in daily life one may also encounter affective expressions by groups, e.g. an angry mob or an exhilarated concert crowd. In what way is brain activity modulated when several individuals express similar rather than different emotions? We investigated this question using an experimental design in which we presented two stimuli simultaneously, with same or different emotional expressions. We hypothesized that, in the case of two same-emotion stimuli, brain activity would be enhanced, while in the case of two different emotions, one emotion would interfere with the effect of the other. The results showed that the simultaneous perception of different affective body expressions leads to a deactivation of the amygdala and a reduction of cortical activity. It was revealed that the processing of fearful bodies, compared with different-emotion bodies, relied more strongly on saliency and action triggering regions in inferior parietal lobe and insula, while happy bodies drove the occipito-temporal cortex more strongly. We showed that this design could be used to uncover important differences between brain networks underlying fearful and happy emotions. The enhancement of brain activity for unambiguous affective signals expressed by several people simultaneously supports adaptive behaviour in critical situations. PMID:27025242

  17. Clear signals or mixed messages: inter-individual emotion congruency modulates brain activity underlying affective body perception.

    Science.gov (United States)

    de Borst, A W; de Gelder, B

    2016-08-01

    The neural basis of emotion perception has mostly been investigated with single face or body stimuli. However, in daily life one may also encounter affective expressions by groups, e.g. an angry mob or an exhilarated concert crowd. In what way is brain activity modulated when several individuals express similar rather than different emotions? We investigated this question using an experimental design in which we presented two stimuli simultaneously, with same or different emotional expressions. We hypothesized that, in the case of two same-emotion stimuli, brain activity would be enhanced, while in the case of two different emotions, one emotion would interfere with the effect of the other. The results showed that the simultaneous perception of different affective body expressions leads to a deactivation of the amygdala and a reduction of cortical activity. It was revealed that the processing of fearful bodies, compared with different-emotion bodies, relied more strongly on saliency and action triggering regions in inferior parietal lobe and insula, while happy bodies drove the occipito-temporal cortex more strongly. We showed that this design could be used to uncover important differences between brain networks underlying fearful and happy emotions. The enhancement of brain activity for unambiguous affective signals expressed by several people simultaneously supports adaptive behaviour in critical situations. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  18. Reaction of photochemical resists used in screen printing under the influence of digitally modulated ultra violet light

    Science.gov (United States)

    Gmuender, T.

    2017-02-01

    Different chemical photo-reactive emulsions are used in screen printing for stencil production. Depending on the bandwidth, optical power and depth of field from the optical system, the reaction / exposure speed has a diverse value. In this paper, the emulsions get categorized and validated in a first step. After that a mathematical model gets developed and adapted due to heuristic experience to estimate the exposure speed under the influence of digitally modulated ultra violet (UV) light. The main intention is to use the technical specifications (intended wavelength, exposure time, distance to the stencil, electrical power, stencil configuration) in the emulsion data sheet primary written down with an uncertainty factor for the end user operating with large projector arc lamps and photo films. These five parameters are the inputs for a mathematical formula which gives as an output the exposure speed for the Computer to Screen (CTS) machine calculated for each emulsion / stencil setup. The importance of this work relies in the possibility to rate with just a few boundaries the performance and capacity of an exposure system used in screen printing instead of processing a long test series for each emulsion / stencil configuration.

  19. Intermittent fasting modulates IgA levels in the small intestine under intense stress: a mouse model.

    Science.gov (United States)

    Lara-Padilla, Eleazar; Godínez-Victoria, Marycarmen; Drago-Serrano, Maria Elisa; Reyna-Garfias, Humberto; Arciniega-Martínez, Ivonne Maciel; Abarca-Rojano, Edgar; Cruz-Hernández, Teresita Rocío; Campos-Rodríguez, Rafael

    2015-08-15

    Intermittent fasting prolongs the lifespan and unlike intense stress provides health benefits. Given the role of the immunoglobulin A (IgA) in the intestinal homeostasis, the aim of this study was to assess the impact of intermittent fasting plus intense stress on secretory IgA (SIgA) production and other mucosal parameters in the duodenum and ileum. Two groups of six mice, with intermittent fasting or fed ad libitum for 12weeks, were submitted to a session of intense stress by a bout of forced swimming. Unstressed ad libitum fed or intermittently fasted groups were included as controls. After sacrifice, we evaluated intestinal SIgA and plasma adrenal hormones, lamina propria IgA+ plasma-cells, mRNA expression of polymeric immunoglobulin receptor, α- and J-chains in the liver and intestinal mucosa, as well as pro- (tumor necrosis factor-α, interleukin-6 and Interferon-γ) and anti- (interleukin-2, -4, -10 and transforming growth factor-β) inflammatory cytokines in mucosal samples. Under intense stress, intermittent fasting down- or up-modulated the levels of most parameters in the duodenum and ileum, respectively while up-regulated corticosterone levels without affecting epinephrine. Our data suggest intermittent fasting plus intense stress elicited neuroendocrine pathways that differentially controlled IgA and pIgR expression in duodenum and ileum. These findings provide experimental foundations for a presumable impact of intermittent fasting under intense stress on the intestinal homeostasis or inflammation by triggering or reducing the IgA production in ileum or duodenum respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. [Nocioceptive pain, neuropathic pain and pain memory].

    Science.gov (United States)

    Montero-Homs, Jordi

    2009-01-01

    Pain is a cognitive evaluation. Its appearance in the new functional image systems is promising. Nocioceptive pain, usually acute or persistent, is useful to prevent animals from getting injured. Chronic pain is disease per se: It is due to a sensitisation phenomena and pain memory with an important relationship with emotions. Neuropathic pain is a neurological symptom due to a somatosensorial system dysfunction. In this case, axonal ectopic generation of impulses and synaptic hyperexcitability occurs. In persistent cases, sensitisation phenomenon and memory of pain appear together with neuropathic pain. Pain treatment should be physiopathologicaly orientated. Pain units, specialized in analgesic treatment and some invasive techniques, are usually competent in the treatment of nocioceptive pain. Neuropathic pain should have a neurologic diagnosis and treatment. But neurologist need to be more and more interested in the chronic pain related with memory and sensitisation: better knowledge of the cerebral mechanisms in this phenomenon can add to this pathology in our field.

  1. The periodontal pain paradox: Difficulty on pain assesment in dental patients (The periodontal pain paradox hypothesis

    Directory of Open Access Journals (Sweden)

    Haryono Utomo

    2006-12-01

    Full Text Available In daily dental practice, the majority of patients’ main complaints are related to pain. Most patients assume that all pains inside the oral cavity originated from the tooth. One particular case is thermal sensitivity; sometimes patients were being able to point the site of pain, although there is neither visible caries nor secondary caries in dental radiograph. In this case, gingival recession and dentin hypersensitivity are first to be treated to eliminate the pain. If these treatments failed, pain may misdiagnose as pulpal inflammation and lead to unnecessary root canal treatment. Study in pain during periodontal instrumentation of plaque-related periodontitis revealed that the majority of patients feel pain and discomfort during probing and scaling. It seems obvious because an inflammation, either acute or chronic is related to a lowered pain threshold. However, in contrast, in this case report, patient suffered from chronic gingivitis and thermal sensitivity experienced a relative pain-free sensation during probing and scaling. Lowered pain threshold which accompanied by a blunted pain perception upon periodontal instrumentation is proposed to be termed as the periodontal pain paradox. The objective of this study is to reveal the possibility of certain factors in periodontal inflammation which may involved in the periodontal pain paradox hypothesis. Patient with thermal hypersensitivity who was conducted probing and scaling, after the relative pain-free instrumentation, thermal hypersensitivity rapidly disappeared. Based on the successful periodontal treatment, it is concluded that chronic gingivitis may modulate periodontal pain perception which termed as periodontal pain paradox

  2. 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.

  3. Sensory pain qualities in neuropathic pain.

    Science.gov (United States)

    Mackey, Sean; Carroll, Ian; Emir, Birol; Murphy, T Kevin; Whalen, Ed; Dumenci, Levent

    2012-01-01

    The qualities of chronic neuropathic pain (NeP) may be informative about the different mechanisms of pain. We previously developed a 2-factor model of NeP that described an underlying structure among sensory descriptors on the Short-Form McGill Pain Questionnaire. The goal of this study was to confirm the correlated 2-factor model of NeP. Individual descriptive scores from the Short-Form McGill Pain Questionnaire were analyzed. Confirmatory factor analysis was used to test a correlated 2-factor model. Factor 1 (stabbing pain) was characterized by high loadings on stabbing, sharp, and shooting sensory items; factor 2 (heavy pain) was characterized by high loadings on heavy, gnawing, and aching items. Results of the confirmatory factor analysis strongly supported the correlated 2-factor model. This article validates a model that describes the qualities of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. These data suggest that specific pain qualities may be associated with pain mechanisms or may be useful for predicting treatment response. Copyright © 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.

  4. Compact electro-thermal modeling of a SiC MOSFET power module under short-circuit conditions

    DEFF Research Database (Denmark)

    Ceccarelli, Lorenzo; Reigosa, Paula Diaz; Bahman, Amir Sajjad

    2017-01-01

    A novel physics-based, electro-thermal model which is capable of estimating accurately the short-circuit behavior and thermal instabilities of silicon carbide MOSFET multi-chip power modules is proposed in this paper. The model has been implemented in PSpice and describes the internal structure...... of the module, including stray elements in the multi-chip layout, self-heating effect, drain leakage current and threshold voltage mismatch. A lumped-parameter thermal network is extracted in order to estimate the internal temperature of the chips. The case study is a half-bridge power module from CREE with 1...

  5. A randomized, Phase IIb study investigating oliceridine (TRV130), a novel µ-receptor G-protein pathway selective (μ-GPS) modulator, for the management of moderate to severe acute pain following abdominoplasty.

    Science.gov (United States)

    Singla, Neil; Minkowitz, Harold S; Soergel, David G; Burt, David A; Subach, Ruth Ann; Salamea, Monica Y; Fossler, Michael J; Skobieranda, Franck

    2017-01-01

    Oliceridine (TRV130), a novel μ-receptor G-protein pathway selective (μ-GPS) modulator, was designed to improve the therapeutic window of conventional opioids by activating G-protein signaling while causing low β-arrestin recruitment to the μ receptor. This randomized, double-blind, patient-controlled analgesia Phase IIb study was conducted to investigate the efficacy, safety, and tolerability of oliceridine compared with morphine and placebo in patients with moderate to severe pain following abdominoplasty (NCT02335294; oliceridine is an investigational agent not yet approved by the US Food and Drug Administration). Patients were randomized to receive postoperative regimens of intravenous oliceridine (loading/patient-controlled demand doses [mg/mg]: 1.5/0.10 [regimen A]; 1.5/0.35 [regimen B]), morphine (4.0/1.0), or placebo with treatment initiated within 4 hours of surgery and continued as needed for 24 hours. Two hundred patients were treated (n=39, n=39, n=83, and n=39 in the oliceridine regimen A, oliceridine regimen B, morphine, and placebo groups, respectively). Patients were predominantly female (n=198 [99%]) and had a mean age of 38.2 years, weight of 71.2 kg, and baseline pain score of 7.7 (on 11-point numeric pain rating scale). Patients receiving the oliceridine regimens had reductions in average pain scores (model-based change in time-weighted average versus placebo over 24 hours) of 2.3 and 2.1 points, respectively ( P =0.0001 and P =0.0005 versus placebo); patients receiving morphine had a similar reduction (2.1 points; P opioids; no serious AEs were reported with oliceridine. These results suggest that oliceridine may provide effective, rapid analgesia in patients with moderate to severe postoperative pain, with an acceptable safety/tolerability profile and potentially wider therapeutic window than morphine.

  6. Spinal Gap Junction Channels in Neuropathic Pain

    OpenAIRE

    Jeon, Young Hoon; Youn, Dong Ho

    2015-01-01

    Damage to peripheral nerves or the spinal cord is often accompanied by neuropathic pain, which is a complex, chronic pain state. Increasing evidence indicates that alterations in the expression and activity of gap junction channels in the spinal cord are involved in the development of neuropathic pain. Thus, this review briefly summarizes evidence that regulation of the expression, coupling, and activity of spinal gap junction channels modulates pain signals in neuropathic pain states induced...

  7. Cancer pain

    International Nuclear Information System (INIS)

    Swerdlow, M.; Ventafridda, V.

    1987-01-01

    This book contains 13 chapters. Some of the chapter titles are: Importance of the Problem; Neurophysiology and Biochemistry of Pain; Assessment of Pain in Patients with Cancer; Drug Therapy; Chemotherapy and Radiotherapy for Cancer Pain; Sympton Control as it Relates to Pain Control; and Palliative Surgery in Cancer Pain Treatment

  8. Pain, objectivity and history: understanding pain stigma.

    Science.gov (United States)

    Goldberg, Daniel S

    2017-12-01

    The primary claim of this paper is that understanding the stigma so commonly endured by chronic pain sufferers today in the USA and the UK is unlikely without proper appreciation of the history of pain. Ameliorating such stigma is an ethical imperative, and yet most approaches eschew even an attempt to trace connections between historical attitudes, practices and beliefs towards pain and the stigmatisation so many pain sufferers currently endure. The manuscript aims to help fill this gap by framing pain in the modern era in context of two crucial intellectual schemes that waxed in the 19th and 20th centuries: mechanical objectivity and somaticism. The analysis explains these frameworks and applies them to exploration of primary sources connected to contested pain conditions such as railway spine. By properly situating the historical roots of what it means to cite the 'subjectivity' of pain as a problem, the modern roots of stigmatising attitudes and practices towards chronic pain sufferers become much clearer. The manuscript concludes by suggesting that interventions expressly intended to target the root causes of such stigma are much more likely to be successful than approaches that proceed in ignorance of the historical forces shaping and driving pain stigma in the present. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Classification and Characteristics of Pain Associated with Parkinson's Disease

    Science.gov (United States)

    Young Blood, Marcelo Rezende; Munhoz, Renato Puppi

    2016-01-01

    Neuropsychiatric symptoms and pain are among the most common nonmotor symptoms of Parkinson's disease (PD). The correlation between pain and PD has been recognized since its classic descriptions. Pain occurs in about 60% of PD patients, two to three times more frequent in this population than in age matched healthy individuals. It is an early and potentially disabling symptom that can precede motor symptoms by several years. The lower back and lower extremities are the most commonly affected areas. The most used classification for pain in PD defines musculoskeletal, dystonic, central, or neuropathic/radicular forms. Its different clinical characteristics, variable relationship with motor symptoms, and inconsistent response to dopaminergic drugs suggest that the mechanism underlying pain in PD is complex and multifaceted, involving the peripheral nervous system, generation and amplification of pain by motor symptoms, and neurodegeneration of areas related to pain modulation. Although pain in DP is common and a significant source of disability, its clinical characteristics, pathophysiology, classification, and management remain to be defined. PMID:27800210

  10. Analysis of the thermo-mechanical behaviour of the DEMO Water-Cooled Lithium Lead breeding blanket module under normal operation steady state conditions

    Energy Technology Data Exchange (ETDEWEB)

    Di Maio, P.A.; Arena, P. [Dipartimento di Energia, Ingegneria dell’Informazione e Modelli Matematici, Università di Palermo, Viale delle Scienze, 90128 Palermo (Italy); Aubert, J. [CEA Saclay, DEN/DANS/DM2S/SEMT, 91191 Gif sur Yvette Cedex (France); Bongiovì, G. [Dipartimento di Energia, Ingegneria dell’Informazione e Modelli Matematici, Università di Palermo, Viale delle Scienze, 90128 Palermo (Italy); Chiovaro, P., E-mail: pierluigi.chiovaro@unipa.it [Dipartimento di Energia, Ingegneria dell’Informazione e Modelli Matematici, Università di Palermo, Viale delle Scienze, 90128 Palermo (Italy); Giammusso, R. [ENEA – C.R. Brasimone, 40032 Camugnano (Italy); Li Puma, A. [CEA Saclay, DEN/DANS/DM2S/SEMT, 91191 Gif sur Yvette Cedex (France); Tincani, A. [ENEA – C.R. Brasimone, 40032 Camugnano (Italy)

    2015-10-15

    Highlights: • A DEMO WCLL blanket module thermo-mechanical behaviour has been investigated. • Two models of the WCLL blanket module have been set-up adopting a code based on FEM. • The water flow domain in the module has been considered. • A set of uncoupled steady state thermo-mechanical analyses has been carried out. • Critical temperature is not overcome. Safety verifications are generally satisfied. - Abstract: Within the framework of DEMO R&D activities, a research cooperation has been launched between ENEA, the University of Palermo and CEA to investigate the thermo-mechanical behaviour of the outboard equatorial module of the DEMO1 Water-Cooled Lithium Lead (WCLL) blanket under normal operation steady state scenario. The research campaign has been carried out following a theoretical–computational approach based on the Finite Element Method (FEM) and adopting a qualified commercial FEM code. In particular, two different 3D FEM models (Model 1 and Model 2), reproducing respectively the central and the lateral poloidal–radial slices of the WCLL blanket module, have been set up. A particular attention has been paid to the modelling of water flow domain, within both the segment box channels and the breeder zone tubes, to simulate realistically the coolant-box thermal coupling. Results obtained are herewith reported and critically discussed.

  11. Increased pain sensitivity in accident-related chronic pain patients with comorbid posttraumatic stress

    DEFF Research Database (Denmark)

    Vaegter, Henrik Bjarke; Andersen, Tonny Elmose; Harvold, Mathea

    2018-01-01

    OBJECTIVES: Posttraumatic stress disorder (PTSD) is prevalent in chronic pain, and associated with increased pain, hyperalgesia and psychological distress. This study aimed to investigate anti-nociceptive and pro-nociceptive pain mechanisms, pain intensity, and psychological distress (depression......, anxiety, pain catastrophizing, and fear of movement) in patients with accident-related chronic spinal pain with (N=44) and without (N=64) comorbid PTSD characteristics. METHODS: Cuff algometry was performed on lower legs to assess pressure pain threshold (cPPT), tolerance (cPTT), temporal summation...... of pain (TSP: increase in pain scores to ten repeated stimulations), and conditioning pain modulation (CPM: increase in cPPT during cuff pain conditioning on the contralateral leg). Warmth detection threshold (WDT) and heat pain threshold (HPT) at the hand were also assessed. Clinical pain intensity...

  12. Repetitive treatment with diluted bee venom reduces neuropathic pain via potentiation of locus coeruleus noradrenergic neuronal activity and modulation of spinal NR1 phosphorylation in rats.

    Science.gov (United States)

    Kang, Suk-Yun; Roh, Dae-Hyun; Yoon, Seo-Yeon; Moon, Ji-Young; Kim, Hyun-Woo; Lee, Hye-Jung; Beitz, Alvin J; Lee, Jang-Hern

    2012-02-01

    We previously demonstrated that a single injection of diluted bee venom (DBV) temporarily alleviates thermal hyperalgesia, but not mechanical allodynia, in neuropathic rats. The present study was designed to determine whether repetitive injection of DBV produces more potent analgesic effects on neuropathy-induced nociception and whether those effects are associated with increased neuronal activity in the locus coeruleus (LC) and with the suppression of spinal NMDA receptor NR1 subunit phosphorylation (pNR1). DBV (.25 mg/kg) was administered subcutaneously twice a day for 2 weeks beginning on day 15 post-chronic constrictive injury surgery. Pain responses were examined and potential changes in LC Fos expression and spinal pNR1 expression were determined. Repetitive DBV administration significantly reduced mechanical allodynia, as well as thermal hyperalgesia. The activity of LC noradrenergic neurons was increased and spinal pNR1 expression was significantly suppressed by repetitive DBV as compared with those of vehicle or single DBV injection. These suppressive effects of repetitive DBV on neuropathic pain and spinal pNR1 were prevented by intrathecal pretreatment of idazoxan, an alpha-2 adrenoceptor antagonist. These results indicate that repetitive DBV produces potent analgesic effects on neuropathic pain and this is associated with the activation of the LC noradrenergic system and with a reduction in spinal pNR1. The results of current study demonstrate that repetitive administration of DBV significantly suppresses neuropathic pain. Furthermore, this study provides mechanistic information that repetitive treatment of DBV can produce more potent analgesic effect than single DBV treatment, indicating a potential novel strategy for the management of chronic pain. Copyright © 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.

  13. Fantom pain: Case report

    Directory of Open Access Journals (Sweden)

    Marić Sanja S.

    2017-01-01

    Full Text Available Background Phantom limb pain is a common problem after limb amputation (41-85%. It is described as an extremely painful sensation in the missing part of the body that can last for hours, days or even years. It is considered to arise from cortical reorganization, although many factors can increase the risk of phantom limb pain: pain before surgery, age and sex of the patients, the time elapsed since surgery, stump pain, inadequate prosthesis. Phantom limb pain therapy is very complicated. Case report We reported a case of 80-year-old patient suffering from phantom limb pain and phantom sensation 25 years after the amputation of his left leg due to the injury. The patient has pain at the site of amputation, sensation that he has the leg and that it occupies an unusual position and almost daily exhausting phantom limb pain (6-9 visual analogue scale - VAS with disturbed sleep and mood. We managed to reduce the pain under 4 VAS and decrease the patient suffering by combining drugs from the group of coanalgetics (antidepressants, antiepileptics, non-pharmacological methods (transcutaneous electroneurostimulation - TENS, mirror therapy and femoral nerve block in the place of disarticulation of the left thigh. Conclusion Phantom limb pain therapy is multimodal, exhausting for both the patient and the physician and it is often unsuccessful. The combination of different pharmacological and non-pharmacological modalities can give satisfactory therapeutic response.

  14. Back Pain

    Science.gov (United States)

    ... Accessed May 29, 2015. Adult acute and subacute low back pain. Bloomington, Minn.: Institute for Clinical Systems Improvement. http://www.icsi.org/low_back_pain/adult_low_back_pain__8.html. Accessed June ...

  15. Abdominal Pain

    Science.gov (United States)

    ... to ease your pain. For instance, eat smaller meals if your pain is accompanied by indigestion. Avoid ... http://www.mayoclinic.org/symptoms/abdominal-pain/basics/definition/SYM-20050728 . Mayo Clinic Footer Legal Conditions and ...

  16. Knee pain

    Science.gov (United States)

    Pain - knee ... Knee pain can have different causes. Being overweight puts you at greater risk for knee problems. Overusing your knee can trigger knee problems that cause pain. If you have a history of arthritis, it ...

  17. Breast pain

    Science.gov (United States)

    Pain - breast; Mastalgia; Mastodynia; Breast tenderness ... There are many possible causes for breast pain. For example, changes in the level of of hormones during menstruation or pregnancy often cause breast pain. Some swelling and tenderness just before ...

  18. Foot pain

    Science.gov (United States)

    Pain - foot ... Foot pain may be due to: Aging Being on your feet for long periods of time Being overweight A ... sports activity Trauma The following can cause foot pain: Arthritis and gout . Common in the big toe, ...

  19. Eye pain

    Science.gov (United States)

    Ophthalmalgia; Pain - eye ... Pain in the eye can be an important symptom of a health problem. Make sure you tell your health care provider if you have eye pain that does not go away. Tired eyes or ...

  20. Wrist pain

    Science.gov (United States)

    Pain - wrist; Pain - carpal tunnel; Injury - wrist; Arthritis - wrist; Gout - wrist; Pseudogout - wrist ... Carpal tunnel syndrome: A common cause of wrist pain is carpal tunnel syndrome . You may feel aching, ...

  1. Ankle pain

    Science.gov (United States)

    Pain - ankle ... Ankle pain is often due to an ankle sprain. An ankle sprain is an injury to the ligaments, which ... the joint. In addition to ankle sprains, ankle pain can be caused by: Damage or swelling of ...

  2. 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

  3. Personality and temperament correlates of pain catastrophizing in young adolescents

    NARCIS (Netherlands)

    P.E.H.M. Muris (Peter); C.M.G. Meesters (Cor); M.F.C.M. Van Den Hout (Mari F. C. M.); S. Wessels (Sylvia); I.H.A. Franken (Ingmar); E.G.C. Rassin (Eric)

    2007-01-01

    textabstractPain catastrophizing is generally viewed as an important cognitive factor underlying chronic pain. The present study examined personality and temperament correlates of pain catastrophizing in a sample of young adolescents (N = 132). Participants completed the Pain Catastrophizing Scale

  4. Postoperative pain

    DEFF Research Database (Denmark)

    Kehlet, H; Dahl, J B

    1993-01-01

    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...... 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...

  5. The endocannabinoid system and pain.

    Science.gov (United States)

    Guindon, Josée; Hohmann, Andrea G

    2009-12-01

    The therapeutic potential of cannabinoids has been the topic of extensive investigation following the discovery of cannabinoid receptors and their endogenous ligands. Cannabinoid receptors and their endogenous ligands are present at supraspinal, spinal and peripheral levels. Cannabinoids suppress behavioral responses to noxious stimulation and suppress nociceptive processing through activation of cannabinoid CB(1) and CB(2) receptor subtypes. Endocannabinoids, the brain's own cannabis-like substances, share the same molecular target as Delta(9)-tetrahydrocannabinol, the main psychoactive component in cannabis. Endocannabinoids serve as synaptic circuit breakers and regulate multiple physiological and pathological conditions, e.g. regulation of food intake, immunomodulation, inflammation, analgesia, cancer, addictive behavior, epilepsy and others. This review will focus on uncovering the roles of anandamide and 2-arachidonoylglycerol, the two best characterized endocannabinoids identified to date, in controlling nociceptive responding. The roles of anandamide and 2-arachidonoylglycerol, released under physiological conditions, in modulating nociceptive responding at different levels of the neuraxis will be emphasized in this review. Effects of modulation of endocannabinoid levels through inhibition of endocannabinoid hydrolysis and uptake is also compared with effects of exogenous administration of synthetic endocannabinoids in acute, inflammatory and neuropathic pain models. Finally, the therapeutic potential of the endocannabinoid signaling system is discussed in the context of identifying novel pharmacotherapies for the treatment of pain.

  6. Period Pain

    Science.gov (United States)

    ... pain relievers such as nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs include ibuprofen and naproxen. Besides relieving pain, NSAIDs reduce the amount of prostaglandins that your uterus ...

  7. Modulation of intersubband light absorption and interband photoluminescence in double GaAs/AlGaAs quantum wells under strong lateral electric fields

    Energy Technology Data Exchange (ETDEWEB)

    Balagula, R. M., E-mail: rmbal@spbstu.ru; Vinnichenko, M. Ya., E-mail: mvin@spbstu.ru; Makhov, I. S.; Firsov, D. A.; Vorobjev, L. E. [Peter the Great Saint-Petersburg Polytechnic University (Russian Federation)

    2016-11-15

    The effect of a lateral electric field on the mid-infrared absorption and interband photoluminescence spectra in double tunnel-coupled GaAs/AlGaAs quantum wells is studied. The results obtained are explained by the redistribution of hot electrons between quantum wells and changes in the space charge in the structure. The hot carrier temperature is determined by analyzing the intersubband light absorption and interband photoluminescence modulation spectra under strong lateral electric fields.

  8. Finite Control Set–Model Predictive Control with Modulation to Mitigate Harmonic Component in Output Current for a Grid-Connected Inverter under Distorted Grid Conditions

    OpenAIRE

    Tien Hai Nguyen; Kyeong-Hwa Kim

    2017-01-01

    This paper presents an improved current control strategy for a three-phase grid-connected inverter under distorted grid conditions. In terms of performance, it is important for a grid-connected inverter to maintain the harmonic contents of inverter output currents below the specified limit even when the grid is subject to harmonic distortion. To address this problem, this paper proposes a modulated finite control set–model predictive control (FCS-MPC) scheme, which effectively mitigates the h...

  9. 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.

  10. Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

    Science.gov (United States)

    Greenwood-Van Meerveld, Beverley; Johnson, Anthony C.

    2017-01-01

    Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS). Early life stress (ELS) is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for stress

  11. A randomized, Phase IIb study investigating oliceridine (TRV130, a novel µ-receptor G-protein pathway selective (µ-GPS modulator, for the management of moderate to severe acute pain following abdominoplasty

    Directory of Open Access Journals (Sweden)

    Singla N

    2017-10-01

    Full Text Available Neil Singla,1 Harold S Minkowitz,2 David G Soergel,3 David A Burt,3 Ruth Ann Subach,3 Monica Y Salamea,3 Michael J Fossler,3 Franck Skobieranda3 1Lotus Clinical Research, Pasadena, CA, 2Memorial Hermann Memorial City Medical Center, Houston, TX, 3Trevena, Inc, King of Prussia, PA, USA Background: Oliceridine (TRV130, a novel µ-receptor G-protein pathway selective (µ-GPS modulator, was designed to improve the therapeutic window of conventional opioids by activating G-protein signaling while causing low β-arrestin recruitment to the µ receptor. This randomized, double-blind, patient-controlled analgesia Phase IIb study was conducted to investigate the efficacy, safety, and tolerability of oliceridine compared with morphine and placebo in patients with moderate to severe pain following abdominoplasty (NCT02335294; oliceridine is an investigational agent not yet approved by the US Food and Drug Administration. Methods: Patients were randomized to receive postoperative regimens of intravenous oliceridine (loading/patient-controlled demand doses [mg/mg]: 1.5/0.10 [regimen A]; 1.5/0.35 [regimen B], morphine (4.0/1.0, or placebo with treatment initiated within 4 hours of surgery and continued as needed for 24 hours. Results: Two hundred patients were treated (n=39, n=39, n=83, and n=39 in the oliceridine regimen A, oliceridine regimen B, morphine, and placebo groups, respectively. Patients were predominantly female (n=198 [99%] and had a mean age of 38.2 years, weight of 71.2 kg, and baseline pain score of 7.7 (on 11-point numeric pain rating scale. Patients receiving the oliceridine regimens had reductions in average pain scores (model-based change in time-weighted average versus placebo over 24 hours of 2.3 and 2.1 points, respectively (P=0.0001 and P=0.0005 versus placebo; patients receiving morphine had a similar reduction (2.1 points; P<0.0001 versus placebo. A lower prevalence of adverse events (AEs related to nausea, vomiting, and respiratory

  12. An Insight to High Humidity-Caused Friction Modulation of Brake by Numerical Modeling of Dynamic Meniscus under Shearing

    Directory of Open Access Journals (Sweden)

    Liangbiao Chen

    2015-05-01

    Full Text Available To obtain an insight to high humidity-caused friction modulation in brake pad-rotor interface, the adhesion phenomenon due to a liquid bridge is simulated using an advanced particle method by varying the shearing speed of the interface. The method, called generalized interpolation material point for fluid-solid interactions (GIMP-FSI, was recently developed from the material point method (MPM for fluid-solid interactions at small scales where surface tension dominates, thus suitable for studying the partially wet brake friction due to high humidity at a scale of 10 m. Dynamic capillary effects due to surface tension and contact angles are simulated. Adhesion forces calculated by GIMP-FSI are consistent with those from the existing approximate meniscus models. Moreover, the numerical results show that capillary effects induce modulations of adhesion as slip speed changes. In particular, the adhesion modulation could be above 30% at low speed. This finding provides insights into how the high humidity-caused friction could cause modulations of brake, which are unable to be achieved by conventional models. Therefore, the numerical analysis helps to elucidate the complex friction mechanisms associated with brakes that are exposed to high humidity environments.

  13. Synaptic Homeostasis and Allostasis in the Dentate Gyrus Caused by Inflammatory and Neuropathic Pain Conditions

    Directory of Open Access Journals (Sweden)

    Rui-Rui Wang

    2018-01-01

    Full Text Available It has been generally accepted that pain can cause imbalance between excitation and inhibition (homeostasis at the synaptic level. However, it remains poorly understood how this imbalance (allostasis develops in the CNS under different pain conditions. Here, we analyzed the changes in both excitatory and inhibitory synaptic transmission and modulation of the dentate gyrus (DG under two pain conditions with different etiology and duration. First, it was revealed that the functions of the input-output (I/O curves for evoked excitatory postsynaptic currents (eEPSCs following the perforant path (PP stimulation were gained under both acute inflammatory and chronic neuropathic pain conditions relative to the controls. However, the functions of I/O curves for the PP-evoked inhibitory postsynaptic currents (eIPSCs differed between the two conditions, namely it was greatly gained under inflammatory condition, but was reduced under neuropathic condition in reverse. Second, both the frequency and amplitude of miniature IPSCs (mIPSCs were increased under inflammatory condition, however a decrease in frequency of mIPSCs was observed under neuropathic condition. Finally, the spike discharge of the DG granule cells in response to current injection was significantly increased by neuropathic pain condition, however, no different change was found between inflammatory pain condition and the control. These results provide another line of evidence showing homeostatic and allostatic modulation of excitatory synaptic transmission by inhibitory controls under different pathological pain conditions, hence implicating use of different therapeutic approaches to maintain the homeostasis between excitation and inhibition while treating different conditions of pathological pain.

  14. [Pain at the neonatal unit under a perspective of nursing staff from a university hospital, Rbeiraõ Peto, SP, Bazil].

    Science.gov (United States)

    Scochi, Carmen Gracinda Silvan; Carletti, Mariângela; Nunes, Rachel; Furtado, Maria Cândida de Carvalho; Leite, Adriana Moraes

    2006-01-01

    This descriptive study from a qualitative approach aims to describe how the nursing team understands pain assessment and management in newborns at a Neonatal Intensive Care Unit (NICU). The subjects are 16 nursing professionals. The nursing staff identifies pain when behavioral and physiological changes are present. They use the NIPS scale, although it is not effective in clinical practice. Subjects reveal difficulties in making a difference between pain and stress responses in daily work. They are worried about correct pain management in newborns. The search of knowledge about pain is still incipient, and subjects mostly obtain it through their experiences in newborn care and by exchanging experiences with other professionals. The nursing team needs greater access to specific literature about neonatal pain and training courses that can optimize pain management, thus contributing to a better care capacity and to the newborn's quality of life.

  15. Imaging of painful scoliosis

    Energy Technology Data Exchange (ETDEWEB)

    Davies, Alun; Saifuddin, Asif [Royal National Orthopaedic Hospital Trust, Department of Radiology, London (United Kingdom)

    2009-03-15

    Scoliosis is defined as a lateral deviation of the spine from the normal plumb line. Commonly, there is a rotational component and deviation also in the sagittal plane (kyphosis or hyperlordosis). When scoliosis presents in adults, it is often painful. In contrast, back pain in a child is considered rare, and serious underlying pathology should be excluded, particularly since idiopathic scoliosis is typically painless. A painful scoliosis in a child or adolescent, especially if the patient has a left-sided curve, should be examined thoroughly. The aim of this review is to illustrate the causes of a painful scoliosis in children, adolescents and adults. (orig.)

  16. Back Pain with Leg Pain.

    Science.gov (United States)

    Vulfsons, Simon; Bar, Negev; Eisenberg, Elon

    2017-07-01

    The clinical diagnostic dilemma of low back pain that is associated with lower limb pain is very common. In relation to back pain that radiates to the leg, the International Association for the Study of Pain (IASP) states: "Pain in the lower limb should be described specifically as either referred pain or radicular pain. In cases of doubt no implication should be made and the pain should be described as pain in the lower limb." Bogduks' editorial in the journal PAIN (2009) helps us to differentiate and define the terms somatic referred pain, radicular pain, and radiculopathy. In addition, there are other pathologies distal to the nerve root that could be relevant to patients with back pain and leg pain such as plexus and peripheral nerve involvement. Hence, the diagnosis of back pain with leg pain can still be challenging. In this article, we present a patient with back and leg pain. The patient appears to have a radicular pain syndrome, but has no neurological impairment and shows signs of myofascial involvement. Is there a single diagnosis or indeed two overlapping syndromes? The scope of our article encompasses the common diagnostic possibilities for this type of patient. A discussion of treatment is beyond the scope of this article and depends on the final diagnosis/diagnoses made.

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

    DEFF Research Database (Denmark)

    Vaegter, Henrik Bjarke; 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...

  18. Muscle pain

    African Journals Online (AJOL)

    Key Summary Points. • Muscle pain, known as myalgia, can be in one targeted area or across many muscles, occurring with overexertion or overuse of these muscles. • Pain can be classified as acute or chronic pain and further categorized as nociceptive or neuropathic. • Causes of muscle pain include stress, physical ...

  19. Conjugated Linoleic Acid Supplementation under a High-Fat Diet Modulates Stomach Protein Expression and Intestinal Microbiota in Adult Mice

    OpenAIRE

    Chaplin, Alice; Parra, Pilar; Serra, Francisca; Palou, Andreu

    2015-01-01

    The gastrointestinal tract constitutes a physiological interface integrating nutrient and microbiota-host metabolism. Conjugated linoleic acids (CLA) have been reported to contribute to decreased body weight and fat accretion. The modulation by dietary CLA of stomach proteins related to energy homeostasis or microbiota may be involved, although this has not been previously analysed. This is examined in the present study, which aims to underline the potential mechanisms of CLA which contribute...

  20. Insufficient Evidence Supports the Use of Low-Level Laser Therapy to Accelerate Tooth Movement, Prevent Orthodontic Relapse, and Modulate Acute Pain During Orthodontic Treatment.

    Science.gov (United States)

    Farsaii, Adrian; Al-Jewair, Thikriat

    2017-09-01

    Efficacy of low-level laser therapy in accelerating tooth movement, preventing relapse and managing acute pain during orthodontic treatment in humans: A systematic review. Sonesson M, De Geer E, Subraian J, Petrén S. BMC Oral Health 2017;17:11. No funding was obtained for this study TYPE OF STUDY/DESIGN: Systematic review. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Bifacial solar cell measurements under standard test conditions and the impact on cell-to-module loss analysis

    Science.gov (United States)

    Singh, Jai Prakash; Chai, Jing; Hsian Saw, Min; Khoo, Yong Sheng

    2017-08-01

    Bifacial cells are conventionally measured using gold-plated chuck, which is conductive and reflective. This measurement setup does not portray the actual operating conditions of the bifacial cells in a module. The reflective chuck causes an overestimation of the current due to the cell transmittance for the infrared light. The conductive chuck creates a shorter current flow path in the rear side of the cell and causes an over inflation of the fill factor measurement. In this study, we characterize and quantitatively analyze the difference between the bifacial cell measurements on different mounting chucks and calculate the cell-to-module (CTM) loss. To characterize the optical behavior of the bifacial cell and module, we perform external quantum efficiency, reflectance and transmittance measurements. The electrical behavior of the bifacial cell is studied using in-house developed software Griddler. Using Griddler, we calculate the difference in the fill factor of the bifacial cell due to the measurement using a conductive and non-conductive chuck, and estimate the corresponding CTM resistive losses.

  2. Efficient and Robust Detection of GFSK Signals under Dispersive Channel, Modulation Index, and Carrier Frequency Offset Conditions

    Directory of Open Access Journals (Sweden)

    Stephan Weiss

    2005-09-01

    Full Text Available Gaussian frequency shift keying is the modulation scheme specified for Bluetooth. Signal adversities typical in Bluetooth networks include AWGN, multipath propagation, carrier frequency, and modulation index offsets. In our effort to realise a robust but efficient Bluetooth receiver, we adopt a high-performance matched-filter-based detector, which is near optimal in AWGN, but requires a prohibitively costly filter bank for processing of K bits worth of the received signal. However, through filtering over a single bit period and performing phase propagation of intermediate results over successive single-bit stages, we eliminate redundancy involved in providing the matched filter outputs and reduce its complexity by up to 90% (for K=9. The constant modulus signal characteristic and the potential for carrier frequency offsets make the constant modulus algorithm (CMA suitable for channel equalisation, and we demonstrate its effectiveness in this paper. We also introduce a stochastic gradient-based algorithm for carrier frequency offset correction, and show that the relative rotation between successive intermediate filter outputs enables us to detect and correct offsets in modulation index.

  3. L- and U-shaped heat pipes thermal modules with twin fans for cooling of electronic system under variable heat source areas

    Science.gov (United States)

    Wang, Jung-Chang

    2014-04-01

    This study utilizes a versatile superposition method with thermal resistance network analysis to design and experiment on a thermal module with embedded six L-shaped or two U-shaped heat pipes and plate fins under different fan speeds and heat source areas. This type of heat pipes-heat sink module successively transfer heat capacity from a heat source to the heat pipes, the heat sink and their surroundings, and are suitable for cooling electronic systems via forced convection mechanism. The thermal resistances contain all major components from the thermal interface through the heat pipes and fins. Thermal performance testing shows that the lowest thermal resistances of the representative L- and U-shaped heat pipes-heat sink thermal modules are respectively 0.25 and 0.17 °C/W under twin fans of 3,000 RPM and 30 × 30 mm2 heat sources. The result of this work is a useful thermal management method to facilitate rapid analysis.

  4. Neurological diseases and pain

    Science.gov (United States)

    2012-01-01

    Chronic pain is a frequent component of many neurological disorders, affecting 20–40% of patients for many primary neurological diseases. These diseases result from a wide range of pathophysiologies including traumatic injury to the central nervous system, neurodegeneration and neuroinflammation, and exploring the aetiology of pain in these disorders is an opportunity to achieve new insight into pain processing. Whether pain originates in the central or peripheral nervous system, it frequently becomes centralized through maladaptive responses within the central nervous system that can profoundly alter brain systems and thereby behaviour (e.g. depression). Chronic pain should thus be considered a brain disease in which alterations in neural networks affect multiple aspects of brain function, structure and chemistry. The study and treatment of this disease is greatly complicated by the lack of objective measures for either the symptoms or the underlying mechanisms of chronic pain. In pain associated with neurological disease, it is sometimes difficult to obtain even a subjective evaluation of pain, as is the case for patients in a vegetative state or end-stage Alzheimer's disease. It is critical that neurologists become more involved in chronic pain treatment and research (already significant in the fields of migraine and peripheral neuropathies). To achieve this goal, greater efforts are needed to enhance training for neurologists in pain treatment and promote greater interest in the field. This review describes examples of pain in different neurological diseases including primary neurological pain conditions, discusses the therapeutic potential of brain-targeted therapies and highlights the need for objective measures of pain. PMID:22067541

  5. DNA Methylation Modulates Nociceptive Sensitization after Incision.

    Directory of Open Access Journals (Sweden)

    Yuan Sun

    Full Text Available DNA methylation is a key epigenetic mechanism controlling DNA accessibility and gene expression. Blockade of DNA methylation can significantly affect pain behaviors implicated in neuropathic and inflammatory pain. However, the role of DNA methylation with regard to postoperative pain has not yet been explored. In this study we sought to investigate the role of DNA methylation in modulating incisional pain and identify possible targets under DNA methylation and contributing to incisional pain. DNA methyltranferase (DNMT inhibitor 5-Aza-2'-deoxycytidine significantly reduced incision-induced mechanical allodynia and thermal sensitivity. Aza-2'-deoxycytidine also reduced hindpaw swelling after incision, suggesting an anti-inflammatory effect. Global DNA methylation and DNMT3b expression were increased in skin after incision, but none of DNMT1, DNMT3a or DNMT3b was altered in spinal cord or DRG. The expression of proopiomelanocortin Pomc encoding β-endorphin and Oprm1 encoding the mu-opioid receptor were upregulated peripherally after incision; moreover, Oprm1 expression was further increased under DNMT inhibitor treatment. Finally, local peripheral injection of the opioid receptor antagonist naloxone significantly exacerbated incision-induced mechanical hypersensitivity. These results suggest that DNA methylation is functionally relevant to incisional nociceptive sensitization, and that mu-opioid receptor signaling might be one methylation regulated pathway controlling sensitization after incision.

  6. Pain Drawings Improve Subgrouping of Low Back Pain Patients.

    Science.gov (United States)

    Hüllemann, Philipp; Keller, Thomas; Kabelitz, Maria; Freynhagen, Rainer; Tölle, Thomas; Baron, Ralf

    2017-03-01

    Subgrouping of low back pain (LBP) patients may be improved when pain drawings are combined with the painDETECT (PD-Q) questionnaire. We hypothesized that (1) different LBP subgroups determined by their pain radiation show different clinical patterns and (2) the occurrence of neuropathic symptoms depends on pain radiation. A total of 19,263 acute ( 3 months) LBP patients were allocated prospectively into 4 groups based on the location of pain drawings on a manikin and compared regarding neuropathic pain components, functionality, depression, pain intensity, and surgical interventions. All items were investigated at baseline and follow-up visits. Group I was composed of patients with axial LBP without radiating pain; group II, LBP with radiation into the thigh; group III, LBP with radiation into the shank; and group IV, LBP with radiation into the feet. Side-dependent pain radiation was assessed additionally. Depression, functionality, and pain intensity showed no clinically relevant differences, whereas PD-Q scores and the probability to rate positive for neuropathic pain increased with more distally radiating pain. Surgery and medication intake were most frequent in group IV. Follow-up analyses showed that only axial LBP became more neuropathic, whereas pain intensity decreased over time. Radicular patterns of pain drawings in LBP patients indicate severe pain conditions with the most neuropathic components, while axial LBP has the fewest. For the categorization of LBP, pain drawings help explain the underlying mechanism of pain, which might further improve mechanism-based treatment when used in clinical routines and research. © 2016 World Institute of Pain.

  7. A life cycle analysis of polymer solar cell modules prepared using roll-to-roll methods under ambient conditions

    DEFF Research Database (Denmark)

    Espinosa Martinez, Nieves; García-Valverde, Rafael; Urbina, Antonio

    2011-01-01

    A life cycle analysis was performed on a full roll-to-roll coating procedure used for the manufacture of flexible polymer solar cell modules. The process known as ProcessOne employs a polyester substrate with a sputtered layer of the transparent conductor indium-tin-oxide (ITO). The ITO film...... was processed into the required pattern using a full roll-to-roll process, employing screen printing of an etch resist and then applying etching, stripping, washing and drying procedures. The three subsequent layers; ZnO, P3HT:PCBM and PEDOT:PSS were slot-die coated and the silver back electrode was screen...

  8. Persistent idiopathic facial pain.

    Science.gov (United States)

    Benoliel, Rafael; Gaul, Charly

    2017-06-01

    Background Persistent idiopathic facial pain (PIFP) is a chronic disorder recurring daily for more than two hours per day over more than three months, in the absence of clinical neurological deficit. PIFP is the current terminology for Atypical Facial Pain and is characterized by daily or near daily pain that is initially confined but may subsequently spread. Pain cannot be attributed to any pathological process, although traumatic neuropathic mechanisms are suspected. When present intraorally, PIFP has been termed 'Atypical Odontalgia', and this entity is discussed in a separate article in this special issue. PIFP is often a difficult but important differential diagnosis among chronic facial pain syndromes. Aim To summarize current knowledge on diagnostic criteria, differential diagnosis, pathophysiology and management of PIFP. Methods We present a narrative review reporting current literature and personal experience. Additionally, we discuss and differentiate the common differential diagnoses associated with PIFP including traumatic trigeminal neuropathies, regional myofascial pain, atypical neurovascular pains and atypical trigeminal neuropathic pains. Results and conclusion The underlying pathophysiology in PIFP is still enigmatic, however neuropathic mechanisms may be relevant. PIFP needs interdisciplinary collaboration to rule out and manage secondary causes, psychiatric comorbidities and other facial pain syndromes, particularly trigeminal neuralgia. Burden of disease and psychiatric comorbidity screening is recommended at an early stage of disease, and should be addressed in the management plan. Future research is needed to establish clear diagnostic criteria and treatment strategies based on clinical findings and individual pathophysiology.

  9. Conjugated Linoleic Acid Supplementation under a High-Fat Diet Modulates Stomach Protein Expression and Intestinal Microbiota in Adult Mice.

    Directory of Open Access Journals (Sweden)

    Alice Chaplin

    Full Text Available The gastrointestinal tract constitutes a physiological interface integrating nutrient and microbiota-host metabolism. Conjugated linoleic acids (CLA have been reported to contribute to decreased body weight and fat accretion. The modulation by dietary CLA of stomach proteins related to energy homeostasis or microbiota may be involved, although this has not been previously analysed. This is examined in the present study, which aims to underline the potential mechanisms of CLA which contribute to body weight regulation. Adult mice were fed either a normal fat (NF, 12% kJ content as fat or a high-fat (HF, 43% kJ content as fat diet. In the latter case, half of the animals received daily oral supplementation of CLA. Expression and content of stomach proteins and specific bacterial populations from caecum were analysed. CLA supplementation was associated with an increase in stomach protein expression, and exerted a prebiotic action on both Bacteroidetes/Prevotella and Akkermansia muciniphila. However, CLA supplementation was not able to override the negative effects of HF diet on Bifidobacterium spp., which was decreased in both HF and HF+CLA groups. Our data show that CLA are able to modulate stomach protein expression and exert a prebiotic effect on specific gut bacterial species.

  10. Conjugated Linoleic Acid Supplementation under a High-Fat Diet Modulates Stomach Protein Expression and Intestinal Microbiota in Adult Mice.

    Science.gov (United States)

    Chaplin, Alice; Parra, Pilar; Serra, Francisca; Palou, Andreu

    2015-01-01

    The gastrointestinal tract constitutes a physiological interface integrating nutrient and microbiota-host metabolism. Conjugated linoleic acids (CLA) have been reported to contribute to decreased body weight and fat accretion. The modulation by dietary CLA of stomach proteins related to energy homeostasis or microbiota may be involved, although this has not been previously analysed. This is examined in the present study, which aims to underline the potential mechanisms of CLA which contribute to body weight regulation. Adult mice were fed either a normal fat (NF, 12% kJ content as fat) or a high-fat (HF, 43% kJ content as fat) diet. In the latter case, half of the animals received daily oral supplementation of CLA. Expression and content of stomach proteins and specific bacterial populations from caecum were analysed. CLA supplementation was associated with an increase in stomach protein expression, and exerted a prebiotic action on both Bacteroidetes/Prevotella and Akkermansia muciniphila. However, CLA supplementation was not able to override the negative effects of HF diet on Bifidobacterium spp., which was decreased in both HF and HF+CLA groups. Our data show that CLA are able to modulate stomach protein expression and exert a prebiotic effect on specific gut bacterial species.

  11. Thermal and Electrical Characterization of a Semi-Transparent Dye-Sensitized Photovoltaic Module under Real Operating Conditions

    Directory of Open Access Journals (Sweden)

    Cristina Cornaro

    2018-01-01

    Full Text Available Dye-sensitized solar cell technology is having an important role in renewable energy research due to its features and low-cost manufacturing processes. Devices based on this technology appear very well suited for integration into glazing systems due to their characteristics of transparency, color tuning and manufacturing directly on glass substrates. Field data of thermal and electrical characteristics of dye-sensitized solar modules (DSM are important since they can be used as input of building simulation models for the evaluation of their energy saving potential when integrated into buildings. However, still few studies in the literature provide this information. The study presented here aims to contribute to fill this lack providing a thermal and electrical characterization of a DSM in real operating conditions using a method developed in house. This method uses experimental data coming from test boxes exposed outdoor and dynamic simulation to provide thermal transmittance (U-value and solar heat gain coefficient (SHGC of a DSM prototype. The device exhibits a U-value of 3.6 W/m2·K, confirmed by an additional measurement carried on in the lab using a heat flux meter, and a SHGC of 0.2, value compliant with literature results. Electrical characterization shows an increase of module power with respect to temperature resulting DSM being suitable for integration in building facades.

  12. Effect of modulated ultrahigh frequency field on behavior and hormone level in female rats under emotional stress

    Energy Technology Data Exchange (ETDEWEB)

    Rasulov, M.M.

    The effect of a modulated electromagnetic field (MEMF) (field frequency of 40 MHz and modulated frequency of 50 Hz, 1 h exposure daily for 30 days) on behavior and level of sexual hormones, determined from the length of the estrous cycle and of its separate phases, was studied in female Wistar rats subjected to sexual deprivation. The ratio of frequency of running to number of vertical positions (R:V) was used as an index. Activity of rats declined during the 1-h exposure to MEMF; this may indicate the direct effect of MEMF on the central nervous system. Analysis of behavior after MEMF treatments ceased showed that the R:V ratio increased from 3.2:1 to 3:1 in month 3 and reached 2:1 in month 5. The relative significance of sexual behavior (lordosis, licking of perineum) more than double in comparison with the initial level. The findings support the existence of individual differences in sensitivity to a UHF field. The data on the estrous cycle indicate the tranquilizing effect of a UHF field on the neuroendocrine system and the greater resistance of individual animals exposed to MEMF to the development of sexual neurosis. 12 references, 2 figures.

  13. Automatic Frequency Identification under Sample Loss in Sinusoidal Pulse Width Modulation Signals Using an Iterative Autocorrelation Algorithm

    Directory of Open Access Journals (Sweden)

    Alejandro S