uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Gordh, T
Alternative names
Publications (10 of 71) Show all publications
Ericson, H., Abu Hamdeh, S., Freyhult, E., Stiger, F., Backryd, E., Svenningsson, A., . . . Kultima, K. (2019). Anti-inflammatory drugs with more penetration into the central nervous system may contribute to the treatment of trigeminal neuralgia Reply [Letter to the editor]. Pain, 160(12), 2898-2899
Open this publication in new window or tab >>Anti-inflammatory drugs with more penetration into the central nervous system may contribute to the treatment of trigeminal neuralgia Reply
Show others...
2019 (English)In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 160, no 12, p. 2898-2899Article in journal, Letter (Other academic) Published
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-407269 (URN)10.1097/j.pain.0000000000001699 (DOI)000512908700024 ()31725083 (PubMedID)
Available from: 2020-03-23 Created: 2020-03-23 Last updated: 2020-03-23Bibliographically approved
Ericson, H., Abu Hamdeh, S., Freyhult, E., Stiger, F., Bäckryd, E., Svenningsson, A., . . . Kultima, K. (2019). Cerebrospinal fluid biomarkers of inflammation in trigeminal neuralgia patients operated with microvascular decompression. Pain, 160(11), 2603-2611
Open this publication in new window or tab >>Cerebrospinal fluid biomarkers of inflammation in trigeminal neuralgia patients operated with microvascular decompression
Show others...
2019 (English)In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 160, no 11, p. 2603-2611Article in journal (Refereed) Published
Abstract [en]

Compression of the trigeminal root entry zone by a blood vessel can cause trigeminal neuralgia (TN). However, a neurovascular conflict does not explain all cases of TN, and TN can exist without a neurovascular contact. A common observation during microvascular decompression surgery to treat TN is arachnoiditis in the region of the trigeminal nerve. Thus, aberrant inflammatory mechanisms may be involved in the pathophysiology of TN but information about the role of inflammation in TN is scarce. We used Proximity Extension Assay technology to analyse the levels of 92 protein biomarkers related to inflammation in lumbar cerebrospinal fluid from patients with TN (n = 27) before and after microvascular decompression compared to individuals without TN. We aimed to analyse the pattern of inflammation-related proteins in order to improve our understanding of the pathophysiology of TN. The main finding was that immunological protein levels in the cerebrospinal fluid from patients with TN decreased after surgery towards levels observed in healthy controls. Two proteins seemed to be of specific interest for TN: TRAIL and TNF-beta. Thus, inflammatory activity might be one important mechanism in TN.

National Category
Neurology
Research subject
Neurosurgery
Identifiers
urn:nbn:se:uu:diva-401710 (URN)10.1097/j.pain.0000000000001649 (DOI)000512906800019 ()31373951 (PubMedID)
Funder
Magnus Bergvall Foundation
Available from: 2020-01-08 Created: 2020-01-08 Last updated: 2020-03-19Bibliographically approved
Lind, A.-L., Just, D., Mikus, M., Fredolini, C., Ioannou, M., Gerdle, B., . . . Manberg, A. (2019). CSF levels of apolipoprotein C1 and autotaxin found to associate with neuropathic pain and fibromyalgia. Journal of Pain Research, 12, 2875-2889
Open this publication in new window or tab >>CSF levels of apolipoprotein C1 and autotaxin found to associate with neuropathic pain and fibromyalgia
Show others...
2019 (English)In: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 12, p. 2875-2889Article in journal (Refereed) Published
Abstract [en]

Objective: Neuropathic pain and fibromyalgia are two common and poorly understood chronic pain conditions that lack satisfactory treatments, cause substantial suffering and societal costs. Today, there are no biological markers on which to base chronic pain diagnoses, treatment choices or to understand the pathophysiology of pain for the individual patient. This study aimed to investigate cerebrospinal fluid (CSF) protein profiles potentially associated with fibromyalgia and neuropathic pain. Methods: CSF samples were collected from 25 patients with neuropathic pain (two independent sets, n=14 patients for discovery, and n=11 for verification), 40 patients with fibromyalgia and 134 controls without neurological disease from two different populations. CSF protein profiling of 55 proteins was performed using antibody suspension bead array technology. Results: We found increased levels of apolipoprotein C1 (APOC1) in CSF of neuropathic pain patients compared to controls and there was a trend for increased levels also in fibromyalgia patients. In addition, levels of ectonucleotide pyrophosphatase family member 2 (ENPP2, also referred to as autotaxin) were increased in the CSF of fibromyalgia patients compared to all other groups including patients with neuropathic pain. Conclusion: The increased levels of APOC1 and ENPP2 found in neuropathic pain and fibromyalgia patients may shed light on the underlying mechanisms of these conditions. Further investigation is required to elucidate their role in maintaining pain and other main symptoms of these disorders.

Place, publisher, year, edition, pages
Dove Medical Press LTD, 2019
Keywords
cerebrospinal fluid, neuropathic pain, fibromyalgia, antibody suspension bead arrays, APOC1, ENPP2
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-396441 (URN)10.2147/JPR.S215348 (DOI)000490123900002 ()31686904 (PubMedID)
Funder
VinnovaSwedish Research CouncilEU, FP7, Seventh Framework Programme, 607616
Available from: 2019-11-13 Created: 2019-11-13 Last updated: 2019-11-22Bibliographically approved
Hysing, E.-B., Smith, L., Thulin, M., Karlsten, R., Bothelius, K. & Gordh, T. (2019). Detection of systemic inflammation in severely impaired chronic pain patients and effects of a multimodal pain rehabilitation program. Scandinavian Journal of Pain, 19(2), 235-244
Open this publication in new window or tab >>Detection of systemic inflammation in severely impaired chronic pain patients and effects of a multimodal pain rehabilitation program
Show others...
2019 (English)In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 19, no 2, p. 235-244Article in journal (Refereed) Published
Abstract [en]

Background and aims: Recent research indicates a previously unknown low-grade systemic or neurogenic inflammation in groups of chronic pain (CP) patients. Low-grade inflammation may have an important role in symptoms that have previously not been well depicted: widespread pain, tiredness and cognitive dysfunctions frequently seen in severely impaired CP patients. This study aimed to investigate the plasma inflammatory profile in a group of very complex CP patients at baseline and at a 1-year follow-up after participation in a cognitive behavior therapy (CBT)-based multimodal pain rehabilitation program (PRP).

Methods: Blood samples were collected from 52 well-characterized CP patients. Age- and sex-matched healthy blood donors served as controls. The samples were analyzed with a multiple Proximal Extension Analysis allowing a simultaneous analysis of 92 inflammation-related proteins consisting mainly of cytokines, chemokines and growth-factors. At follow-up, 1-year after participation in the RPR samples from 28 patients were analyzed. The results were confirmed by a multi-array technology that allows quantitative estimation.

Results: Clear signs of increased inflammatory activity were detected in the CP patients. Accepting a false discovery rate (FDR) of 5%, there were significant differences in 43/92 inflammatory biomarkers compared with the controls. In three biomarkers (CXCL5, SIRT2, AXIN1) the expression levels were elevated more than eight times. One year after the PRP, with the patients serving as their own controls, a significant decrease in overall inflammatory activity was found.

Conclusions: Our results indicate that the most impaired CP patients suffer from low-grade chronic systemic inflammation not described earlier with this level of detail. The results may have implications for a better understanding of the cluster of co-morbid symptoms described as the "sickness-syndrome" and the wide-spread pain seen in this group of patients. The decrease in inflammatory biomarkers noted at the follow-up after participation in the PRP may reflect the positive effects obtained on somatic and psycho-social mechanisms involved in the inflammatory process by a rehabilitation program. Besides the PRP, no major changes in medication or lifestyle factors were implemented during the same period. To our knowledge, this is the first study reporting that a PRP may induce inflammatory-reducing effects. Further studies are needed to verify the objective findings in CP patients and address the question of causality that remains to be solved.

Place, publisher, year, edition, pages
WALTER DE GRUYTER GMBH, 2019
Keywords
inflammatory biomarkers, severely impaired pain patients, central inflammation, systemic inflammation, pain rehabilitation program
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-382511 (URN)10.1515/sjpain-2018-0340 (DOI)000463370000003 ()30893060 (PubMedID)
Funder
VinnovaSwedish Research Council, P29797-1
Available from: 2019-04-30 Created: 2019-04-30 Last updated: 2019-04-30Bibliographically approved
Bothelius, K., Hysing, E.-B., Filen, T., Lundeborg, L. & Gordh, T. (2019). Insomnia-related Memory Impairment in Individuals With Very Complex Chronic Pain. COGNITIVE AND BEHAVIORAL NEUROLOGY, 32(3), 164-171
Open this publication in new window or tab >>Insomnia-related Memory Impairment in Individuals With Very Complex Chronic Pain
Show others...
2019 (English)In: COGNITIVE AND BEHAVIORAL NEUROLOGY, ISSN 1543-3633, Vol. 32, no 3, p. 164-171Article in journal (Refereed) Published
Abstract [en]

Objective: To investigate the specific effect of insomnia on neuropsychological functioning in patients with very complex chronic pain. Background: Individuals with insomnia disorder or chronic pain often experience cognitive deficits, with both conditions appearing to correlate with impairments in neuropsychological functions. As insomnia often occurs comorbid with chronic pain, distinguishing the differential effects of these two syndromes on an individual's neuropsychological functioning can be challenging. Comorbid depressive symptoms in these individuals, which may also affect cognitive function, may further obscure the associations between chronic pain, insomnia, and the neuropsychological profile. Methods: The neuropsychological function of 22 individuals with very complex chronic pain was assessed using specialized tests examining aspects of memory and executive functioning. The severity of insomnia, depression, and anxiety was measured using questionnaires, and pain levels were assessed using a visual analog scale. Pain medications were transformed to the morphine-equivalent daily dose. Results: Insomnia severity was found to predict memory function, accounting for 32.4% of the variance: A 1 SD increase in insomnia severity decreased memory function by 0.57 SD. The negative correlation between insomnia and memory was significant even after controlling for pain level, morphine-equivalent daily dose, and comorbid levels of anxiety and depression. Conclusions: Insomnia severity independently predicted memory function in patients with very complex chronic pain, even after controlling for other factors known to impair cognitive function. Insomnia may possibly explain some of the cognitive impairments related to chronic pain; thus, screening for, and treating, sleep disturbances may be a central aspect of chronic pain rehabilitation.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2019
Keywords
insomnia, chronic pain, memory, neuropsychological functioning
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-396623 (URN)10.1097/WNN.0000000000000196 (DOI)000490483700002 ()31517699 (PubMedID)
Available from: 2019-11-13 Created: 2019-11-13 Last updated: 2019-11-13Bibliographically approved
Feresiadou, A., Nilsson, K., Ingelsson, M., Press, R., Kmezic, I., Nygren, I., . . . Burman, J. (2019). Measurement of sCD27 in the cerebrospinal fluid identifies patients with neuroinflammatory disease. Journal of Neuroimmunology, 332, 31-36
Open this publication in new window or tab >>Measurement of sCD27 in the cerebrospinal fluid identifies patients with neuroinflammatory disease
Show others...
2019 (English)In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 332, p. 31-36Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Laboratory tests to assist in the diagnosis and monitoring of neuroinflammatory diseases are scarce. The soluble form of the CD27 molecule (sCD27) is shed in high concentrations by activated T cells and can be detected in the cerebrospinal fluid. The aim of this study was to investigate whether CSF quantitation of sCD27 could discriminate between inflammatory and non-inflammatory neurological diseases.

METHODS: The concentration of sCD27 was measured using a commercially available ELISA in 803 well-defined subjects from a study cohort comprised of 338 patients with neuroinflammatory disease, 338 with non-inflammatory neurological disease and 127 controls without neurological disease.

RESULTS: The median value of cerebrospinal fluid sCD27 was 64 pg/mL (IQR 0-200) in controls, 58 pg/mL (IQR 0-130) in patients with non-inflammatory disease and 740 pg/mL (IQR 230-1800) in patients with inflammatory disease. The likelihood ratio of having an inflammatory disease was 10 (sensitivity 74% and specificity 93%) if the sCD27 concentration was >250 pg/mL. In patients with a known inflammatory condition, the likelihood ratio of having an infection was 10 (sensitivity 40% and specificity 96%) if the sCD27 concentration was >2500 pg/mL.

CONCLUSIONS: The likelihood of having an inflammatory neurological condition is increased with elevated concentrations of sCD27 in cerebrospinal fluid. Rapid tests of sCD27 should be developed to assist clinicians in diagnosis of neuroinflammatory disease.

National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-381319 (URN)10.1016/j.jneuroim.2019.03.015 (DOI)000470940600004 ()30928869 (PubMedID)
Available from: 2019-04-26 Created: 2019-04-26 Last updated: 2020-02-05Bibliographically approved
Emami Khoonsari, P., Musunri, S., Herman, S., Svensson, C. I., Tanum, L., Gordh, T. & Kultima, K. (2019). Systematic Analysis of the Cerebrospinal Fluid Proteome of Fibromyalgia patients. Journal of Proteomics, 35-43
Open this publication in new window or tab >>Systematic Analysis of the Cerebrospinal Fluid Proteome of Fibromyalgia patients
Show others...
2019 (English)In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, p. 35-43Article in journal (Refereed) Published
Abstract [en]

Fibromyalgia (FM) is a syndrome characterized by widespread muscular pain, fatigue and functional symptoms, which is known to be difficult to diagnose as the various symptoms overlap with many other conditions. Currently, there are no biomarkers for FM, and the diagnosis is made subjectively by the clinicians. We have performed shotgun proteomics on cerebrospinal fluid (CSF) from FM patients and non-pain controls to find potential biomarker candidates for this syndrome. Based on our multivariate and univariate analyses, we found that the relative differences in the CSF proteome between FM patients and controls were moderate. Four proteins, important to discriminate FM patients from non-pain controls, were found: Apolipoprotein C-III, Galectin-3-binding protein, Malate dehydrogenase cytoplasmic and the neuropeptide precursor protein ProSAAS. These proteins are involved in lipoprotein lipase (LPL) activity, inflammatory signaling, energy metabolism and neuropeptide signaling.

Keywords
cerebrospinal fluid, biomarker, chronic pain, fibromyalgia, inflammation, neuroinflammation, mass spectrometry
National Category
Neurosciences Clinical Laboratory Medicine Biomedical Laboratory Science/Technology
Research subject
Bioinformatics; Biology with specialization in Molecular Biology; Chemistry with specialization in Analytical Chemistry; Medical Science; Clinical Chemistry
Identifiers
urn:nbn:se:uu:diva-331615 (URN)10.1016/j.jprot.2018.04.014 (DOI)000450381500006 ()29656018 (PubMedID)
Funder
Magnus Bergvall FoundationLars Hierta Memorial FoundationÅke Wiberg FoundationThe Karolinska Institutet's Research Foundation
Available from: 2017-10-16 Created: 2017-10-16 Last updated: 2019-04-29Bibliographically approved
Philippot, G., Hallgren, S., Gordh, T., Fredriksson, A., Fredriksson, R. & Viberg, H. (2018). A Cannabinoid Receptor Type 1 (CB1R) Agonist Enhances the Developmental Neurotoxicity of Acetaminophen (Paracetamol). Toxicological Sciences, 166(1), 203-212
Open this publication in new window or tab >>A Cannabinoid Receptor Type 1 (CB1R) Agonist Enhances the Developmental Neurotoxicity of Acetaminophen (Paracetamol)
Show others...
2018 (English)In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 166, no 1, p. 203-212Article in journal (Refereed) Published
Abstract [en]

Acetaminophen (AAP; also known as paracetamol) is the most used and only recommended analgesic and antipyretic among pregnant women and young children. However, recent findings in both humans and rodents suggest a link between developmental exposure to AAP and adverse neurobehavioral effects later in life. We hypothesized that the cannabinoid receptor type 1 (CB1R) may be involved in the developmental neurotoxicity of AAP, owing to its interaction with the endocannabinoid system. Here we test if CB1R agonist WIN 55 212-2 (WIN) and AAP can interact when exposure occurs during a neurodevelopmental stage known for increased growth rate and for its vulnerability to AAP exposure. We exposed male NMRI mice on postnatal day 10 to different combinations of AAP and WIN. Adult mice, neonatally co-exposed to AAP and WIN, displayed a significant lack of habituation in the spontaneous behavior test, when compared with controls and single agent exposed mice. These adult adverse effects may at least in part be explained by a reduction of transcript levels of hippocampal synaptophysin (Syp) and tropomyosin receptor kinase B (Trkb), and cerebral cortical fatty acid amide hydroxylase (Faah), 24h after exposure. These findings are consistent with our hypothesis that AAP and WIN can interact when exposure occurs during early postnatal brain development in mice. Assuming our results are relevant for humans, they raise concerns on AAP safety because it is the only recommended analgesic and antipyretic during pregnancy and early life.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
Keywords
developmental toxicity, acetaminophen (paracetamol), CB1R, spontaneous behavior, habituation
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-372828 (URN)10.1093/toxsci/kfy199 (DOI)000453585900016 ()30165669 (PubMedID)
Available from: 2019-01-09 Created: 2019-01-09 Last updated: 2020-03-23Bibliographically approved
Lesniak, A., Aarnio, M., Diwakarla, S., Norberg, T., Nyberg, F. & Gordh, T. (2018). Characterization of the binding site for d-deprenyl in human inflamed synovial membrane.. Life Sciences, 194, 26-33
Open this publication in new window or tab >>Characterization of the binding site for d-deprenyl in human inflamed synovial membrane.
Show others...
2018 (English)In: Life Sciences, ISSN 0024-3205, E-ISSN 1879-0631, Vol. 194, p. 26-33Article in journal (Refereed) Published
Abstract [en]

Aims: D-Deprenyl when used as a positron emission tomography tracer visualizes peripheral inflammation. The major aim of the current study was to identify and investigate the properties of the binding target for D-deprenyl in synovial membrane explants from arthritic patients.

Main methods: Thirty patients diagnosed with arthritis or osteoarthritis were enrolled into the study. Homologous and competitive radioligand binding assays utilizing [H-3]D-deprenyl were performed to investigate the biochemical characteristics of the binding site and assess differences in the binding profile in synovial membranes exhibiting varying levels of inflammation.

Key findings: The [H-3]D-deprenyl binding assay confirmed the existence of a single, saturable population of membrane-bound protein binding sites in synovial membrane homogenates. The macroscopically determined level of inflammation correlated with an increase in [H-3]D-deprenyl binding affinity, without significant alterations in binding site density. Selective monoamine oxidase B inhibitor, selegiline competed for the same site as [H-3]D-deprenyl, but failed to differentiate the samples with regard to their inflammation grade. A monoamine oxidase A inhibitor, pirlindole mesylate showed only weak displacement of [H-3]D-deprenyl binding. No significant alterations in monoamine oxidase B expression was detected, thus it was not confirmed whether it could serve as a marker for ongoing inflammation.

Significance: Our study was the first to show the biochemical characteristics of the [H-3]D-deprenyl binding site in inflamed human synovium. We confirmed that d-deprenyl could differentiate between patients with varying severity of synovitis in the knee joint by binding to a protein target distinct from monoamine oxidase B.

Keywords
Arthritis, Binding target, Monoamine oxidase B, Synovium, d-Deprenyl
National Category
Pharmaceutical Sciences
Research subject
Pharmaceutical Biochemistry; Medical Biochemistry
Identifiers
urn:nbn:se:uu:diva-347601 (URN)10.1016/j.lfs.2017.12.003 (DOI)000425052000004 ()29221756 (PubMedID)
Funder
Swedish Research Council, 9459
Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-18Bibliographically approved
Buratovic, S., Stenerlöw, B., Sundell-Bergman, S., Fredriksson, A., Viberg, H., Gordh, T. & Eriksson, P. (2018). Effects on adult cognitive function after neonatal exposure to clinically relevant doses of ionising radiation and ketamine in mice. British Journal of Anaesthesia, 120(3), 546-554
Open this publication in new window or tab >>Effects on adult cognitive function after neonatal exposure to clinically relevant doses of ionising radiation and ketamine in mice
Show others...
2018 (English)In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 120, no 3, p. 546-554Article in journal (Refereed) Published
Abstract [en]

Background: Radiological methods for screening, diagnostics and therapy are frequently used in healthcare. In infants and children, anaesthesia/sedation is often used in these situations to relieve the patients' perception of stress or pain. Both ionising radiation (IR) and ketamine have been shown to induce developmental neurotoxic effects and this study aimed to identify the combined effects of these in a murine model. Methods: Male mice were exposed to a single dose of ketamine (7.5 mg kg(-1) body weight) s.c. on postnatal day 10. One hour after ketamine exposure, mice were whole body irradiated with 50-200 mGy gamma radiation (Cs-137). Behavioural observations were performed at 2, 4 and 5 months of age. At 6 months of age, cerebral cortex and hippocampus tissue were analysed for neuroprotein levels. Results: Animals co-exposed to IR and ketamine displayed significant (P <= 0.01) lack of habituation in the spontaneous behaviour test, when compared with controls and single agent exposed mice. In the Morris Water Maze test, co-exposed animals showed significant (P <= 0.05) impaired learning and memory capacity in both the spatial acquisition task and the relearning test compared with controls and single agent exposed mice. Furthermore, in co-exposed mice a significantly (P <= 0.05) elevated level of tau protein in cerebral cortex was observed. Single agent exposure did not cause any significant effects on the investigated endpoints. Conclusion: Co-exposure to IR and ketamine can aggravate developmental neurotoxic effects at doses where the single agent exposure does not impact on the measured variables. These findings show that estimation of risk after paediatric low-dose IR exposure, based upon radiation dose alone, may underestimate the consequences for this vulnerable population.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2018
Keywords
cognition, gamma rays, ketamine, mice, tau proteins
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-360552 (URN)10.1016/j.bja.2017.11.099 (DOI)000438191300019 ()29452811 (PubMedID)
Funder
Swedish Radiation Safety Authority
Available from: 2018-09-14 Created: 2018-09-14 Last updated: 2018-09-14Bibliographically approved
Organisations

Search in DiVA

Show all publications