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Search Results: 1 - 10 of 26332 matches for " Martin Ingvar "
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"Anxiebo", placebo, and postoperative pain
Paul Svedman, Martin Ingvar, Torsten Gordh
BMC Anesthesiology , 2005, DOI: 10.1186/1471-2253-5-9
Abstract: Postoperative pain remains a significant clinical problem. Increased pain intensity with increased demand for opioid medication, and/or a relative unresponsiveness to pain treatment was reported both when the analgesia was administered by means of conventional nurse injection regimes and patient-controlled analgesia (PCA). Both the quality of the analgesia, and the sensitivity of postoperative models for assessing analgesic efficacy could be significantly influenced.The findings could be explained by increased penetration of an algesic anxiety-related nocebo influence (which we chose to call "anxiebo") relative to its analgesic placebo counterpart. To counteract this influence, the importance of psychological effects must be acknowledged, and doctors and attending nurses should focus on maintaining trustful therapist-patient relationships throughout the treatment period. The physical mechanism of anxiebo should be further explored, and those at risk for anxiebo better characterized. In addition, future systemic analgesic therapies should be directed towards being prophylactic and continuous to eliminate surgical pain as it appears in order to prevent the anxiebo effect.Addressing anxiebo is the key to developing reproducible models for measuring pain in the postoperative setting, and to improving the accuracy of measurements of the minimum effective analgesic concentration.Anxiebo and placebo act as counterparts postoperatively. The anxiebo state may impair clinical analgesia and reduce the sensitivity of analgesic trials. Ways to minimize anxiebo are discussed.In spite of considerable progress in postoperative analgesia, recent studies show that adequate pain relief remains elusive for a significant fraction of hospitalized surgical patients [1-3]. Continuous awareness of this problem and further efforts to improve treatment are required despite the availability of acute pain services [3]. Surgical treatment and its consequences cause psychological stress, and pain
Mapping of hormones and cortisol responses in patients after Lyme neuroborreliosis
Ivar Tjernberg, Martin Carlsson, Jan Ernerudh, Ingvar Eliasson, Pia Forsberg
BMC Infectious Diseases , 2010, DOI: 10.1186/1471-2334-10-20
Abstract: Twenty patients of a retrospective cohort of patients treated for definite Lyme neuroborreliosis were recruited 2.3 to 3.7 years (median 2.7) after diagnosis, together with 23 healthy controls. Lyme neuroborreliosis patients were stratified into two groups according to a symptom/sign score. All participants underwent anthropometric and physiological investigation as well as an extensive biochemical endocrine investigation including a short high-dose adrenocorticotropic hormone stimulation (Synacthen?) test. In addition to hormonal status, we also examined electrolytes, 25-hydroxy-vitamin D and interleukin-6.Eight patients (40%) had pronounced symptoms 2-3 years after treatment. This group had a higher cortisol response to synacthen as compared with both controls and the Lyme neuroborreliosis patients without remaining symptoms (p < 0.001 for both comparisons). No other significant differences in the various baseline biochemical parameters, anthropometric or physiological data could be detected across groups.Apart from a positive association between the occurrence of long-lasting complaints after Lyme neuroborreliosis and cortisol response to synacthen, no corticotropic insufficiency or other serious hormonal dysfunction was found to be associated with remaining symptoms after treatment for Lyme neuroborreliosis.Lyme borreliosis is the most commonly reported tick-transmitted disease in the northern hemisphere [1]. The overall incidence in the south of Sweden has been reported to be 69 per 100 000 inhabitants and year, with marked regional variability. For instance, the incidence in Kalmar County was reported to be 160 per 100 000 inhabitants and year [2].Clinical manifestations of Lyme borreliosis are diverse and include erythema migrans, neuroborreliosis, arthritis, lymphocytoma, carditis, and acrodermatitis chronica atrophicans. In Sweden, Lyme neuroborreliosis (LNB) is the second most common manifestation after erythema migrans. Current antibiotic treatment recomm
Conditioned Pain Modulation Is Associated with Common Polymorphisms in the Serotonin Transporter Gene
Fredrik Lindstedt,Jonathan Berrebi,Erik Greayer,Tina B. Lonsdorf,Martin Schalling,Martin Ingvar,Eva Kosek
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0018252
Abstract: Variation in the serotonin transporter (5-HTT) gene (SLC6A4) has been shown to influence a wide range of affective processes. Low 5-HTT gene-expression has also been suggested to increase the risk of chronic pain. Conditioned pain modulation (CPM) - i.e. ‘pain inhibits pain’ - is impaired in chronic pain states and, reciprocally, aberrations of CPM may predict the development of chronic pain. Therefore we hypothesized that a common variation in the SLC6A4 is associated with inter-individual variation in CPM. Forty-five healthy subjects recruited on the basis of tri-allelic 5-HTTLPR genotype, with inferred high or low 5-HTT-expression, were included in a double-blind study. A submaximal-effort tourniquet test was used to provide a standardized degree of conditioning ischemic pain. Individualized noxious heat and pressure pain thresholds (PPTs) were used as subjective test-modalities and the nociceptive flexion reflex (NFR) was used to provide an objective neurophysiological window into spinal processing.
Perception of Thermal Pain and the Thermal Grill Illusion Is Associated with Polymorphisms in the Serotonin Transporter Gene
Fredrik Lindstedt,Tina B. Lonsdorf,Martin Schalling,Eva Kosek,Martin Ingvar
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0017752
Abstract: The main aim of this study was to assess if the perception of thermal pain thresholds is associated with genetically inferred levels of expression of the 5-HT transporter (5-HTT). Additionally, the perception of the so-called thermal grill illusion (TGI) was assessed. Forty-four healthy individuals (27 females, 17 males) were selected a-priori based on their 5-HTTLPR/rs25531 (‘tri-allelic 5-HTTLPR’) genotype, with inferred high or low 5-HTT expression. Thresholds for heat- and cold-pain were determined along with the sensory and affective dimensions of the TGI.
Increased Sensitivity to Thermal Pain Following a Single Opiate Dose Is Influenced by the COMT val158met Polymorphism
Karin B. Jensen, Tina B. Lonsdorf, Martin Schalling, Eva Kosek, Martin Ingvar
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006016
Abstract: Increased pain sensitivity after opioid administration (opioid-induced hyperalgesia) and/or repeated painful stimuli is an individually varying and clinically important phenomenon. The functional polymorphism (val158met) of the Catechol-O-methyltransferase (COMT) gene regulates the metabolism of dopamine/noradrenaline. Individuals homozygous for the met158 allele have been reported to have increased pain sensitivity and there are findings of lower μ-opioid system activation during sustained pain. We hypothesized that met/met individuals would exhibit higher pain sensitization and opioid-induced hyperalgesia in response to repeated pain stimuli and an intravenous injection of an opioid drug. Participants were 43 healthy subjects who went through an experiment where five blocks of pain were induced to the hand using a heat probe. After each stimulus subjects rated the pain on a visual analogue scale (VAS) from 0 mm (no pain) to 100 mm (worst possible pain). Before the second stimulus there was an intravenous injection of a rapid and potent opioid drug. At baseline there was no difference in pain ratings between the COMTval158met genotypes, F(2, 39)<1. However, a repeated measures ANOVA for all five stimuli revealed a main effect for COMTval158met genotype, F(2, 36) = 4.17, p = 0.024. Met/met individuals reported significantly more pain compared to val/val, p = 0.010. A pairwise comparison of baseline and the opioid intervention demonstrated that analgesia was induced in all groups (p = 0.042) without a separating effect for genotype (n.s). We suggest that the initial response of the descending pain system is not influenced by the COMTval158met polymorphism but when the system is challenged the difference is revealed. An important clinical implication of this may be that the COMTval158met related differences may be more expressed in individuals where the inhibitory system is already challenged and sensitive, e.g. chronic pain patients. This has to be proven in future studies where the impact of the COMTval158met polymorphism on opioid treatment in patients is addressed.
Serotonin-1A Receptor Polymorphism (rs6295) Associated with Thermal Pain Perception
Fredrik Lindstedt, Bianka Karshikoff, Martin Schalling, Caroline Olgart H?glund, Martin Ingvar, Mats Lekander, Eva Kosek
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043221
Abstract: Background Serotonin (5-HT) is highly involved in pain regulation and serotonin-1A (5-HT1A) receptors are important in determining central 5-HT tone. Accordingly, variation in the 5-HT1A receptor gene (HTR1A) may contribute to inter-individual differences in human pain sensitivity. The minor G-allele of the HTR1A single nucleotide polymorphism (SNP) rs6295 attenuates firing of serotonergic neurons and reduces postsynaptic expression of the receptor. Experiments in rodents suggest that 5-HT1A-agonism modulates pain in opposite directions at mild compared to high noxious intensities. Based upon this and several other similar observations, we hypothesized that G-carriers would exhibit a relative hypoalgesia at mild thermal stimuli but tend towards hyperalgesia at higher noxious intensities. Methods Fourty-nine healthy individuals were selectively genotyped for rs6295. Heat- and cold-pain thresholds were assessed along with VAS-ratings of a range of suprathreshold noxious heat intensities (45°C–49°C). Nociceptive-flexion reflex (NFR) thresholds were also assessed. Results Volunteers did not deviate significantly from Hardy-Weinberg equilibrium. G-carriers were less sensitive to threshold-level thermal pain. This relative hypoalgesia was abolished at suprathreshold noxious intensities where G-carriers instead increased their ratings of heat-pain significantly more than C-homozygotes. No differences with regard to NFR-thresholds emerged. Conclusion/Significance To the best of our knowledge this is the first study of human pain perception on the basis of variation in HTR1A. The results illustrate the importance of including a range of stimulus intensities in assessments of pain sensitivity. In speculation, we propose that an attenuated serotonergic tone may be related to a ‘hypo- to hyperalgesic’ response-pattern. The involved mechanisms could be of clinical interest as variation in pain regulation is known to influence the risk of developing pain pathologies. Further investigations are therefore warranted.
Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans
Eva Kosek, Karin B Jensen, Tina B Lonsdorf, Martin Schalling, Martin Ingvar
Molecular Pain , 2009, DOI: 10.1186/1744-8069-5-37
Abstract: At baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (SA/SA and SA/LG) as compared to those with high expression(LA/LA), p < 0.02. The analgesic effect for the three different genotype groups was linear to degree of 5-HTT expression.This is the first report showing an influence of the triallelic 5-HTTLPR on pain sensitivity or the analgesic effect of opioids in humans. Previously the 5-HTTLPR s-allele has been associated with higher risk of developing chronic pain conditions but in this study we show that the genotype coding for low 5-HTT expression is associated with a better analgesic effect of an opioid. The s-allele has been associated with downregulation of 5-HT1 receptors and we suggest that individuals with a desensitization of 5-HT1 receptors have an increased analgesic response to opioids during acute pain stimuli, but may still be at increased risk of developing chronic pain conditions.Modern pain research has highlighted the importance of central nervous system mechanisms for the regulation of acute and chronic pain. The large individual differences in pain sensitivity, response to analgesic drugs and risk of developing chronic pain is partially explained by genetic factors with impact on the endogenous pain modulation that takes place within the central nervous system [1,2]. The activity of the descending pain inhibitory pathways is largely dependent on dopamine/noradrenalin as well as endogenous opioids and previous studies have shown that polymorphisms in genes coding for μ-opioid receptors and the catecholamine-degrading enzyme catechol-O-methyltransferase (COMT) influence pain responses [3,4]. However, in addition to well known opioidergic pain regulatory mechanism with a k
Evidence for Thalamic Involvement in the Thermal Grill Illusion: An fMRI Study
Fredrik Lindstedt, Bo Johansson, Sofia Martinsen, Eva Kosek, Peter Fransson, Martin Ingvar
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027075
Abstract: Background Perceptual illusions play an important role in untangling neural mechanisms underlying conscious phenomena. The thermal grill illusion (TGI) has been suggested as a promising model for exploring percepts involved in neuropathic pain, such as cold-allodynia (pain arising from contact with innocuous cold). The TGI is an unpleasant/painful sensation from touching juxtapositioned bars of cold and warm innocuous temperatures. Aim To develop an MRI-compatible TGI-unit and explore the supraspinal correlates of the illusion, using fMRI, in a group of healthy volunteers. Methods We constructed a TGI-thermode allowing the rapid presentation of warm(41°C), cold(18°C) and interleaved(41°C+18°C = TGI) temperatures in an fMRI-environment. Twenty volunteers were tested. The affective-motivational (“unpleasantness”) and sensory-disciminatory (“pain-intensity”) dimensions of each respective stimulus were rated. Functional images were analyzed at a corrected α-level <0.05. Results The TGI was rated as significantly more unpleasant and painful than stimulation with each of its constituent temperatures. Also, the TGI was rated as significantly more unpleasant than painful. Thermal stimulation versus neutral baseline revealed bilateral activations of the anterior insulae and fronto-parietal regions. Unlike its constituent temperatures the TGI displayed a strong activation of the right (contralateral) thalamus. Exploratory contrasts at a slightly more liberal threshold-level also revealed a TGI-activation of the right mid/anterior insula, correlating with ratings of unpleasantness(rho = 0.31). Conclusion/Significance To the best of our knowledge, this is the first fMRI-study of the TGI. The activation of the anterior insula is consistent with this region's putative role in processing of homeostatically relevant feeling-states. Our results constitute the first neurophysiologic evidence of thalamic involvement in the TGI. Similar thalamic activity has previously been observed during evoked cold-allodynia in patients with central neuropathic pain. Our results further the understanding of the supraspinal correlates of the TGI-phenomenon and pave the way for future inquiries into if and how it may relate to neuropathic pain.
Limbic Justice—Amygdala Involvement in Immediate Rejection in the Ultimatum Game
Katarina Gospic,Erik Mohlin,Peter Fransson,Predrag Petrovic,Magnus Johannesson,Martin Ingvar
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1001054
Abstract: Imaging studies have revealed a putative neural account of emotional bias in decision making. However, it has been difficult in previous studies to identify the causal role of the different sub-regions involved in decision making. The Ultimatum Game (UG) is a game to study the punishment of norm-violating behavior. In a previous influential paper on UG it was suggested that frontal insular cortex has a pivotal role in the rejection response. This view has not been reconciled with a vast literature that attributes a crucial role in emotional decision making to a subcortical structure (i.e., amygdala). In this study we propose an anatomy-informed model that may join these views. We also present a design that detects the functional anatomical response to unfair proposals in a subcortical network that mediates rapid reactive responses. We used a functional MRI paradigm to study the early components of decision making and challenged our paradigm with the introduction of a pharmacological intervention to perturb the elicited behavioral and neural response. Benzodiazepine treatment decreased the rejection rate (from 37.6% to 19.0%) concomitantly with a diminished amygdala response to unfair proposals, and this in spite of an unchanged feeling of unfairness and unchanged insular response. In the control group, rejection was directly linked to an increase in amygdala activity. These results allow a functional anatomical detection of the early neural components of rejection associated with the initial reactive emotional response. Thus, the act of immediate rejection seems to be mediated by the limbic system and is not solely driven by cortical processes, as previously suggested. Our results also prompt an ethical discussion as we demonstrated that a commonly used drug influences core functions in the human brain that underlie individual autonomy and economic decision making.
Executive Functions Predict the Success of Top-Soccer Players
Torbj?rn Vestberg, Roland Gustafson, Liselotte Maurex, Martin Ingvar, Predrag Petrovic
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0034731
Abstract: While the importance of physical abilities and motor coordination is non-contested in sport, more focus has recently been turned toward cognitive processes important for different sports. However, this line of studies has often investigated sport-specific cognitive traits, while few studies have focused on general cognitive traits. We explored if measures of general executive functions can predict the success of a soccer player. The present study used standardized neuropsychological assessment tools assessing players' general executive functions including on-line multi-processing such as creativity, response inhibition, and cognitive flexibility. In a first cross-sectional part of the study we compared the results between High Division players (HD), Lower Division players (LD) and a standardized norm group. The result shows that both HD and LD players had significantly better measures of executive functions in comparison to the norm group for both men and women. Moreover, the HD players outperformed the LD players in these tests. In the second prospective part of the study, a partial correlation test showed a significant correlation between the result from the executive test and the numbers of goals and assists the players had scored two seasons later. The results from this study strongly suggest that results in cognitive function tests predict the success of ball sport players.
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