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Gordh, T
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Publications (10 of 56) Show all publications
Philippot, G., Gordh, T., Fredriksson, A. & Viberg, H. (2017). Adult neurobehavioral alterations in male and female mice following developmental exposure to paracetamol (acetaminophen): characterization of a critical period. Journal of Applied Toxicology, 37(10), 1174-1181.
Open this publication in new window or tab >>Adult neurobehavioral alterations in male and female mice following developmental exposure to paracetamol (acetaminophen): characterization of a critical period
2017 (English)In: Journal of Applied Toxicology, ISSN 0260-437X, E-ISSN 1099-1263, Vol. 37, no 10, 1174-1181 p.Article in journal (Refereed) Published
Abstract [en]

Paracetamol (acetaminophen) is a widely used non-prescription drug with analgesic and antipyretic properties. Among pregnant women and young children, paracetamol is one of the most frequently used drugs and is considered the first-choice treatment for pain and/or fever. Recent findings in both human and animal studies have shown associations between paracetamol intake during brain development and adverse behavioral outcomes later in life. The present study was undertaken to investigate if the induction of these effects depend on when the exposure occurs during a critical period of brain development and if male and female mice are equally affected. Mice of both sexes were exposed to two doses of paracetamol (30 + 30 mg kg – 1 , 4 h apart) on postnatal days (PND) 3, 10 or 19. Spontaneous behavior, when introduced to a new home environment, was observed at the age of 2 months. We show that adverse effects on adult behavior and cognitive function occurred in both male and female mice exposed to paracetamol on PND 3 and 10, but not when exposed on PND 19. These neurodevelopmental time points in mice correspond to the beginning of the third trimester of pregnancy and the time around birth in humans, supporting existing human data. Considering that paracetamol is the first choice treatment for pain and/or fever during pregnancy and early life, these results may be of great importance for future research and, ultimately, for clinical practice

Keyword
Paracetamol (acetaminophen), developmental neurotoxicity, neonatal mice, critical period, spontaneous behavior, habituation, cognitive impairments
National Category
Neurosciences Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-334493 (URN)10.1002/jat.3473 (DOI)000409913500005 ()28448685 (PubMedID)
Available from: 2017-11-23 Created: 2017-11-23 Last updated: 2018-01-13Bibliographically approved
Backryd, E., Tanum, L., Lind, A.-L., Larsson, A. & Gordh, T. (2017). Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma. Journal of Pain Research, 10.
Open this publication in new window or tab >>Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma
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2017 (English)In: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 10Article in journal (Refereed) Published
Abstract [en]

In addition to central hyperexcitability and impaired top-down modulation, chronic inflammation probably plays a role in the pathophysiology of fibromyalgia (FM). Indeed, on the basis of both animal experiments and human studies involving the analysis of cytokines and other inflammation-related proteins in different body fluids, neuroinflammatory mechanisms are considered to be central to the pathophysiology of many chronic pain conditions. However, concerning FM, previous human plasma/serum and/or cerebrospinal fluid (CSF) cytokine studies have looked only at a few predetermined cytokine candidates. Instead of analyzing only a few substances at a time, we used a new multiplex protein panel enabling simultaneous analysis of 92 inflammation-related proteins. Hence, we investigated the CSF and plasma inflammatory profiles of 40 FM patients compared with CSF from healthy controls (n= 10) and plasma from blood donor controls (n= 46). Using multivariate data analysis by projection, we found evidence of both neuroinflammation (as assessed in CSF) and chronic systemic inflammation (as assessed in plasma). Two groups of proteins (one for CSF and one for plasma) highly discriminating between patients and controls are presented. Notably, we found high levels of CSF chemokine CX3CL1 (also known as fractalkine). In addition, previous findings concerning IL-8 in FM were replicated, in both CSF and plasma. This is the first time that such an extensive inflammatory profile has been described for FM patients. Hence, FM seems to be characterized by objective biochemical alterations, and the lingering characterization of its mechanisms as essentially idiopathic or even psychogenic should be seen as definitively outdated.

Place, publisher, year, edition, pages
DOVE MEDICAL PRESS LTD, 2017
Keyword
cerebrospinal fluid, chemokines, chronic pain, cytokines, fibromyalgia, inflammation
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-319693 (URN)10.2147/JPR.S128508 (DOI)000396320700001 ()
Funder
VINNOVASwedish Research Council, P29797-1
Note

The two first authors contributed equally to this work

Available from: 2017-04-06 Created: 2017-04-06 Last updated: 2017-11-29Bibliographically approved
Tanum, L., Backryd, E., Lind, A.-L., Larsson, A. & Gordh, T. (2017). Evidence of both Systemic Inflammation and Neuroinflammation in Patients with Chronic Widespread Pain. Paper presented at 72nd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), MAY 18-20, 2017, San Diego, CA. Biological Psychiatry, 81(10), S231-S232.
Open this publication in new window or tab >>Evidence of both Systemic Inflammation and Neuroinflammation in Patients with Chronic Widespread Pain
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2017 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 81, no 10, S231-S232 p.Article in journal, Meeting abstract (Other academic) Published
Keyword
Cytokines and Chemokines, chronic pain, Neuroinflammation, immunoinflammation, cerebrospinal fluid
National Category
Neurology Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-331810 (URN)10.1016/j.biopsych.2017.02.443 (DOI)000400348700570 ()
Conference
72nd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), MAY 18-20, 2017, San Diego, CA
Funder
Swedish Research Council
Available from: 2017-10-18 Created: 2017-10-18 Last updated: 2017-10-18Bibliographically approved
Gerdle, B., Ghafouri, B., Ghafouri, N., Backryd, E. & Gordh, T. (2017). Signs of ongoing inflammation in female patients with chronic widespread pain A multivariate, explorative, cross-sectional study of blood samples. Medicine (Baltimore, Md.), 96(9), Article ID e6130.
Open this publication in new window or tab >>Signs of ongoing inflammation in female patients with chronic widespread pain A multivariate, explorative, cross-sectional study of blood samples
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2017 (English)In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 96, no 9, e6130Article in journal (Refereed) Published
Abstract [en]

This cross-sectional study investigates the plasma inflammatory profile of chronic widespread pain CWP) patients compared to healthy controls CON). Rather than analyzing a relatively few substances at a time, we used a new multiplex proximity extension assay PEA) panel that enabled the simultaneous analysis of 92 inflammation-related proteins, mainly cytokines and chemokines. Seventeen women with CWP and 21 female CON participated and a venous blood sample was drawn from all subjects. Pain intensity and pain thresholds for pressure, heat, and cold were registered. A PEA panel 92 proteins) was used to analyze the blood samples. Multivariate data analysis by projection was used in the statistical analyses. Eleven proteins significantly differentiated the CON and CWP subjects R-2=0.58, Q(2)=0.37, analysis of variance of cross-validated predictive residuals P=0.006). It was not possible to significantly regress pain thresholds within each group CON or CWP). Positive significant correlations existed between several proteins and pain intensities in CWP, but the model reliability of the regression was poor. CWP was associated with systemic low-grade inflammation. Larger studies are needed to confirm the results and to investigate which alterations are condition-specific and which are common across chronic pain conditions. The presence of inflammation could promote the spreading of pain, a hallmark sign of CWP. As it has been suggested that prevalent comorbidities to pain (e.g., depression and anxiety, poor sleep, and tiredness) also are associated with inflammation, it will be important to determine whether inflammation may be a common mediator.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2017
Keyword
chemokine, cytokine, fibromyalgia, pain, widespread pain
National Category
General Practice
Identifiers
urn:nbn:se:uu:diva-320360 (URN)10.1097/MD.0000000000006130 (DOI)000395795900011 ()28248866 (PubMedID)
Funder
VINNOVASwedish Research Council, P29797-1 K2015-99x-21874-05-4AFA Insurance, 140341
Available from: 2017-04-19 Created: 2017-04-19 Last updated: 2018-01-13Bibliographically approved
Lind, A.-L., Yu, D., Freyhult, E., Bodolea, C., Ekegren, T., Larsson, A., . . . Kamali-Moghaddam, M. (2016). A Multiplex Protein Panel Applied to Cerebrospinal Fluid Reveals Three New Biomarker Candidates in ALS but None in Neuropathic Pain Patients. PLoS ONE, 11(2), Article ID e0149821.
Open this publication in new window or tab >>A Multiplex Protein Panel Applied to Cerebrospinal Fluid Reveals Three New Biomarker Candidates in ALS but None in Neuropathic Pain Patients
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 2, e0149821Article in journal (Refereed) Published
Abstract [en]

The objective of this study was to develop and apply a novel multiplex panel of solid-phase proximity ligation assays (SP-PLA) requiring only 20 μL of samples, as a tool for discovering protein biomarkers for neurological disease and treatment thereof in cerebrospinal fluid (CSF). We applied the SP-PLA to samples from two sets of patients with poorly understood nervous system pathologies amyotrophic lateral sclerosis (ALS) and neuropathic pain, where patients were treated with spinal cord stimulation (SCS). Forty-seven inflammatory and neurotrophic proteins were measured in samples from 20 ALS patients and 15 neuropathic pain patients, and compared to normal concentrations in CSF from control individuals. Nineteen of the 47 proteins were detectable in more than 95% of the 72 controls. None of the 21 proteins detectable in CSF from neuropathic pain patients were significantly altered by SCS. The levels of the three proteins, follistatin, interleukin-1 alpha, and kallikrein-5 were all significantly reduced in the ALS group compared to age-matched controls. These results demonstrate the utility of purpose designed multiplex SP-PLA panels in CSF biomarker research for understanding neuropathological and neurotherapeutic mechanisms. The protein changes found in the CSF of ALS patients may be of diagnostic interest.

National Category
Neurology Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-281233 (URN)10.1371/journal.pone.0149821 (DOI)000371175700030 ()26914813 (PubMedID)
Funder
Swedish Research CouncilKnut and Alice Wallenberg FoundationEU, European Research Council, 316929EU, European Research Council, 294409
Available from: 2016-03-21 Created: 2016-03-21 Last updated: 2017-11-30Bibliographically approved
Gordh, T. (2016). Analysis of C-reactive protein (CRP) levels in pain patients - Can biomarker studies lead to better understanding of the pathophysiology of pain?. Scandinavian Journal of Pain, 11, 165-166.
Open this publication in new window or tab >>Analysis of C-reactive protein (CRP) levels in pain patients - Can biomarker studies lead to better understanding of the pathophysiology of pain?
2016 (English)In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 11, 165-166 p.Article in journal, Editorial material (Other academic) Published
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-300386 (URN)10.1016/j.sjpain.2016.03.002 (DOI)000378138300033 ()
Available from: 2016-08-08 Created: 2016-08-08 Last updated: 2017-11-28Bibliographically approved
Lesniak, A., Aarnio, M., Jonsson, A., Norberg, T., Nyberg, F. & Gordh, T. (2016). High-throughput screening and radioligand binding studies reveal monoamine oxidase-B as the primary binding target for D-deprenyl. Life Sciences, 152, 231-237.
Open this publication in new window or tab >>High-throughput screening and radioligand binding studies reveal monoamine oxidase-B as the primary binding target for D-deprenyl
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2016 (English)In: Life Sciences, ISSN 0024-3205, E-ISSN 1879-0631, Vol. 152, 231-237 p.Article in journal (Refereed) Published
Abstract [en]

Aims: D-deprenyl is a useful positron emission tomography tracer for visualization of inflammatory processes. Studies with [C-11]-D-deprenyl showed robust uptake in peripheral painful sites of patients with rheumatoid arthritis or chronic whiplash injury. The mechanism of preferential D-deprenyl uptake is not yet known, but the existence of a specific binding site was proposed. Thus, in the present study, we sought to identify the binding site for D-deprenyl and verify the hypothesis about the possibility of monoamine oxidase enzymes as major targets for this molecule. Main methods: A high-throughput analysis of D-deprenyl activity towards 165 G-protein coupled receptors and 84 enzyme targets was performed. Additionally, binding studies were used to verify the competition of [H-3]D-deprenyl with ligands specific for targets identified in the high-throughput screen. Key findings: Our high-throughput investigation identified monoamine oxidase-B, monoamine oxidase-A and angiotensin converting enzyme as potential targets for D-deprenyl. Further competitive [3H] D-deprenyl binding studies with specific inhibitors identified monoamine oxidase-B as the major binding site. No evident high-affinity hits were identified among G-protein coupled receptors. Significance: Our study was the first to utilize a high-throughput screening approach to identify putative D-deprenyl targets. It verified 249 candidate proteins and confirmed the role of monoamine oxidase - B in D-deprenyl binding. Our results add knowledge about the possible mechanism of D-deprenyl binding, which might aid in explaining the increased uptake of this compound in peripheral inflammation. Monoamine oxidase-B will be further investigated in future studies utilizing human inflamed synovium.

Keyword
D-deprenyl High-throughput screening Binding site
National Category
Pharmaceutical Sciences Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-291492 (URN)10.1016/j.lfs.2016.03.058 (DOI)000375728500028 ()27058977 (PubMedID)
Funder
Berzelii Centre EXSELENT, 2013-01495
Available from: 2016-05-03 Created: 2016-05-03 Last updated: 2018-01-10Bibliographically approved
Moen, A., Lind, A.-L., Thulin, M., Kamali-Moghaddam, M., Roe, C., Gjerstad, J. & Gordh, T. (2016). Inflammatory Serum Protein Profiling of Patients with Lumbar Radicular Pain One Year after Disc Herniation. INTERNATIONAL JOURNAL OF INFLAMMATION, Article ID UNSP 3874964.
Open this publication in new window or tab >>Inflammatory Serum Protein Profiling of Patients with Lumbar Radicular Pain One Year after Disc Herniation
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2016 (English)In: INTERNATIONAL JOURNAL OF INFLAMMATION, ISSN 2090-8040, UNSP 3874964Article in journal (Refereed) Published
Abstract [en]

Earlier studies suggest that lumbar radicular pain following disc herniation may be associated with a local or systemic inflammatory process. In the present study, we investigated the serum inflammatory protein profile of such patients. All 45 patients were recruited from Oslo University Hospital, Ulleval, Norway, during the period 2007-2009. The new multiplex proximity extension assay (PEA) technology was used to analyze the levels of 92 proteins. Interestingly, the present data showed that patients with radicular pain 12 months after disc herniation may be different from other patients with regard to many measurable serum cytokines. Given a false discovery rate (FDR) of 0.10 and 0.05, we identified 41 and 13 proteins, respectively, which were significantly upregulated in the patients with severe pain one year after disc herniation. On the top of the list ranked by estimated increase we found C-X-C motif chemokine 5 (CXCM5; 217% increase), epidermal growth factor (EGF; 142% increase), and monocyte chemotactic protein 4 (MCP-4; 70% increase). Moreover, a clear overall difference in the serum cytokine profile between the chronic and the recovered patients was demonstrated. Thus, the present results may be important for future protein serum profiling of lumbar radicular pain patients with regard to prognosis and choice of treatment. We conclude that serum proteins may be measurable molecular markers of persistent pain after disc herniation.

National Category
General Practice
Identifiers
urn:nbn:se:uu:diva-317717 (URN)10.1155/2016/3874964 (DOI)000394106300001 ()27293953 (PubMedID)
Funder
VINNOVASwedish Research Council, P29797-1
Available from: 2017-03-17 Created: 2017-03-17 Last updated: 2018-01-13Bibliographically approved
Bothelius, K., Kyhle, K., Broman, J.-E., Gordh, T. & Fredrikson, M. (2016). Initial Sleep Time Predicts Success in Manual-Guided Cognitive Behavioral Therapy for Insomnia. Behavioural Sleep Medicine, 14(4), 378-388.
Open this publication in new window or tab >>Initial Sleep Time Predicts Success in Manual-Guided Cognitive Behavioral Therapy for Insomnia
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2016 (English)In: Behavioural Sleep Medicine, ISSN 1540-2002, E-ISSN 1540-2010, Vol. 14, no 4, 378-388 p.Article in journal (Refereed) Published
Abstract [en]

Cognitive behavioral therapy produces significant and long-lasting improvement for individuals with insomnia, but treatment resources are scarce. A "stepped care" approach has therefore been proposed, but knowledge is limited on how to best allocate patients to different treatment steps. In this study, 66 primary-care patients with insomnia attended a low-end treatment step: manual-guided cognitive behavioral therapy (CBT) for insomnia delivered by ordinary primary-care personnel. Based on clinically significant treatment effects, subjects were grouped into treatment responders or nonresponders. Baseline data were analyzed to identify predictors for treatment success. Long total sleep time at baseline assessment was the only statistically significant predictor for becoming a responder, and sleep time may thus be important to consider before enrolling patients in low-end treatments.

National Category
Neurology Psychiatry
Identifiers
urn:nbn:se:uu:diva-266762 (URN)10.1080/15402002.2015.1007995 (DOI)000374971100003 ()26323054 (PubMedID)
Available from: 2015-11-10 Created: 2015-11-10 Last updated: 2017-12-01Bibliographically approved
Buhrman, M., Gordh, T. & Andersson, G. (2016). Internet interventions for chronic pain including headache: A systematic review. Internet Interventions, 4, 17-34.
Open this publication in new window or tab >>Internet interventions for chronic pain including headache: A systematic review
2016 (English)In: Internet Interventions, ISSN 2214-7829, Vol. 4, 17-34 p.Article in journal (Refereed) Published
Abstract [en]

Chronic pain is a major health problem and behavioral based treatments have been shown to be effective. However, the availability of these kinds of treatments is scarce and internet-based treatments have been shown to be promising in this area. The objective of the present systematic review is to evaluate internet-based interventions for persons with chronic pain. The specific aims are to do an updated review with a broad inclusion of different chronic pain diagnoses and to assess disability and pain and also measures of catastrophizing, depression and anxiety. A systematic search identified 891 studies and 22 trials were selected as eligible for review. Two of the selected trials included children/youth and five included individuals with chronic headache and/or migraine. The most frequently measured domain reflected in the primary outcomes was interference/disability, followed by catastrophizing. Result across the studies showed a number of beneficial effects. Twelve trials reported significant effects on disability/interference outcomes and pain intensity. Positive effects were also found on psychological variable such as catastrophizing, depression and anxiety. Several studies (n = 12) were assessed to have an unclear level of risk bias. The attrition levels ranged from 4% to 54% where the headache trials had the highest drop-out levels. However, findings suggest that internet-based treatments based on cognitive behavioural therapy (CBT) are efficacious measured with different outcome variables. Results are in line with trials in clinical settings. Meta-analytic statistics were calculated for interference/disability, pain intensity, catastrophizing and mood ratings. Results showed that the effect size for interference/disability was Hedge's g = − 0.39, for pain intensity Hedge's g = − 0.33, for catastrophizing Hedge's g = − 0.49 and for mood variables (depression) Hedge's g = − 0.26.

Keyword
chronic pain, internet, cognitive behavioral therapy
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-284152 (URN)10.1016/j.invent.2015.12.001 (DOI)
Available from: 2016-04-15 Created: 2016-04-15 Last updated: 2017-11-30Bibliographically approved
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