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3. Chronic Pain and the Endocannabinoid System: Smart Lipids - A Novel Therapeutic Option?

Author

Zieglgänsberger, Walter, Brenneisen, Rudolf, Berthele, Achim, Wotjak, Carsten T., Bandelow, Borwin, Tölle, Thomas R., and Lutz, Beat

Subjects
Lipids -- Health aspects, Medical marijuana -- Health aspects, Medical research -- Health aspects, Medicine, Experimental -- Health aspects, Neurons -- Health aspects, Chronic pain -- Health aspects, B cells -- Health aspects, Pain -- Care and treatment, Sex differences (Psychology) -- Health aspects, Stress (Psychology) -- Health aspects, Mental illness -- Health aspects, Health
Abstract

The development of a high-end cannabinoid-based therapy is the result of intense translational research, aiming to convert recent discoveries in the laboratory into better treatments for patients. Novel compounds and new regimes for drug treatment are emerging. Given that previously unreported signaling mechanisms for cannabinoids have been uncovered, clinical studies detailing their high therapeutic potential are mandatory. The advent of novel genomic, optogenetic, and viral tracing and imaging techniques will help to further detail therapeutically relevant functional and structural features. An evolutionarily highly conserved group of neuromodulatory lipids, their receptors, and anabolic and catabolic enzymes are involved in a remarkable variety of physiological and pathological processes and has been termed the endocannabinoid system (ECS). A large body of data has emerged in recent years, pointing to a crucial role of this system in the regulation of the behavioral domains of acquired fear, anxiety, and stress-coping. Besides neurons, also glia cells and components of the immune system can differentially fine-tune patterns of neuronal activity. Dysregulation of ECS signaling can lead to a lowering of stress resilience and increased incidence of psychiatric disorders. Chronic pain may be understood as a disease process evoked by fear-conditioned nociceptive input and appears as the dark side of neuronal plasticity. By taking a toll on every part of your life, this abnormal persistent memory of an aversive state can be more damaging than its initial experience. All strategies for the treatment of chronic pain conditions must consider stress-related comorbid conditions since cognitive factors such as beliefs, expectations, and prior experience (memory of pain) are key modulators of the perception of pain. The anxiolytic and anti-stress effects of medical cannabinoids can substantially modulate the efficacy and tolerability of therapeutic interventions and will help to pave the way to a successful multimodal therapy. Why some individuals are more susceptible to the effects of stress remains to be uncovered. The development of personalized prevention or treatment strategies for anxiety and depression related to chronic pain must also consider gender differences. An emotional basis of chronic pain opens a new horizon of opportunities for developing treatment strategies beyond the repeated sole use of acutely acting analgesics. A phase I trial to determine the pharmacokinetics, psychotropic effects, and safety profile of a novel nanoparticle-based cannabinoid spray for oromucosal delivery highlights a remarkable innovation in galenic technology and urges clinical studies further detailing the huge therapeutic potential of medical cannabis (Lorenzl et al.; this issue). Keywords: Endocannabinoid system, Chronic pain, Novel galenic, Author(s): Walter Zieglgänsberger [a]; Rudolf Brenneisen [b]; Achim Berthele [c]; Carsten T. Wotjak [a]; Borwin Bandelow [d]; Thomas R. Tölle [c]; Beat Lutz [e] Phytocannabinoids Cannabis triggers a complex set [...]

Published
2022
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9. Schmerz

Author

Berthele, Achim, primary and Tölle, Thomas R., additional

Published
2021
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11. Why Europe needs a pain research strategy

Author

Pickering, Gisèle, primary, O’Keeffe, Mary, additional, Bannister, Kirsty, additional, Becker, Susanne, additional, Cottom, Sonia, additional, Cox, Felicia J., additional, Eisenberg, Elon, additional, Finn, David P., additional, Graven‐Nielsen, Thomas, additional, Meeus, Mira, additional, Mouraux, Andre, additional, Tölle, Thomas, additional, Garcia‐Larrea, Luis, additional, and Fullen, Brona M., additional

Published
2023
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13. Paradoxical heat sensation as a manifestation of thermal hypesthesia: a study of 1090 patients with lesions of the somatosensory system

Author

Vollert, Jan, primary, Fardo, Francesca, additional, Attal, Nadine, additional, Baron, Ralf, additional, Bouhassira, Didier, additional, Enax-Krumova, Elena K., additional, Freynhagen, Rainer, additional, Hansson, Per, additional, Jensen, Troels S., additional, Kersebaum, Dilara, additional, Maier, Christoph, additional, Pogatzki-Zahn, Esther, additional, Rice, Andrew S.C., additional, Sachau, Juliane, additional, Schaldemose, Ellen L., additional, Segerdahl, Märta, additional, Sendel, Manon, additional, Tölle, Thomas R., additional, Finnerup, Nanna B., additional, and Treede, Rolf-Detlef, additional

Published
2023
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14. Safety and efficacy of an equimolar mixture of oxygen and nitrous oxide: a randomized controlled trial in patients with peripheral neuropathic pain

Author

Bouhassira, Didier, Perrot, Serge, Riant, Thibault, Martiné-Fabre, Gaelle, Pickering, Gisèle, Maindet, Caroline, Attal, Nadine, Ranque Garnier, Stéphanie, Nguyen, Jean-Paul, Kuhn, Emmanuelle, Viel, Eric, Kieffert, Patrick, Tölle, Thomas, Delorme, Claire, Deleens, Rodrigue, Giniès, Patrick, Corand-Dousset, Virginie, Dal-Col, Clémence, Serrie, Alain, Chevrillon, Emmanuel, Gov, Christian, Ramirez-Gil, Juan Fernando, Delval, Cécile, Schaller, Manuella, Bessière, Baptiste, Houéto, Patrick, and Sommer, Claudia

Published
2020
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15. No pain, still gain (of function): the relation between sensory profiles and the presence or absence of self-reported pain in a large multicenter cohort of patients with neuropathy

Author

Forstenpointner, Julia, Ruscheweyh, Ruth, Attal, Nadine, Baron, Ralf, Bouhassira, Didier, Enax-Krumova, Elena K., Finnerup, Nanna B., Freynhagen, Rainer, Gierthmühlen, Janne, Hansson, Per, Jensen, Troels S., Maier, Christoph, Rice, Andrew S.C., Segerdahl, Märta, Tölle, Thomas, Treede, Rolf-Detlef, and Vollert, Jan

Published
2020
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16. Longitudinal prevalence and determinants of pain in multiple sclerosis: results from the German National Multiple Sclerosis Cohort study

Author

Heitmann, Henrik, Haller, Bernhard, Tiemann, Laura, Mühlau, Mark, Berthele, Achim, Tölle, Thomas R., Salmen, Anke, Ambrosius, Björn, Bayas, Antonios, Asseyer, Susanna, Hartung, Hans-Peter, Heesen, Christoph, Stangel, Martin, Wildemann, Brigitte, Haars, Sarah, Groppa, Sergiu, Luessi, Felix, Kümpfel, Tania, Nischwitz, Sandra, Meuth, Sven G., Klotz, Luisa, Linker, Ralf A., Zettl, Uwe K., Ziemann, Ulf, Tumani, Hayrettin, Tackenberg, Björn, Zipp, Frauke, Wiendl, Heinz, Gold, Ralf, Hemmer, Bernhard, and Ploner, Markus

Published
2020
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18. Neurometabolic correlates of depression and disability in episodic cluster headache

Author

Seifert, Christian L., Valet, Michael, Pfaffenrath, Volker, Boecker, Henning, Rüther, Katharina V., Tölle, Thomas R., and Sprenger, Till

Subjects
Medicine & Public Health, Neuroradiology, Neurosciences, Neurology, Cluster headache, Depression, Disability, Pain intensity, FDG-PET
Abstract

A close association between pain, depression and disability has been shown. However, the neurometabolic correlates of this association have been barely investigated in disease states. Episodic cluster headache is a severe headache syndrome and represents a suitable disease model for the investigation of episodic pain. The aim of this study was to explore the relationship between depression and disability as well as pain scores and brain metabolism in patients with cluster headache during the disease period with repetitive pain attacks, but outside an acute attack. Thirteen patients with cluster headache underwent 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission (FDG-PET) and completed questionnaires on depression and disability as well as a pain visual analogue rating scale (VAS). A positive correlation between the depression scores and glucose metabolism was observed in the insular cortex. A positive correlation between the pain disability scores and brain metabolism was detected in the amygdala. The same applied to the pain visual analogue rating scores. Our data underline the association between severe episodic pain, depression and disability. In addition to this clinical observation, our results stress the importance of the insula and amygdala in pain processing and suffering.

Published
2011

19. Joint European Academy of Neurology–European Pain Federation–Neuropathic Pain Special Interest Group of the International Association for the Study of Pain guidelines on neuropathic pain assessment

Author

Truini, Andrea, primary, Aleksovska, Katina, additional, Anderson, Christopher C., additional, Attal, Nadine, additional, Baron, Ralf, additional, Bennett, David L., additional, Bouhassira, Didier, additional, Cruccu, Giorgio, additional, Eisenberg, Elon, additional, Enax‐Krumova, Elena, additional, Davis, Karen Deborah, additional, Di Stefano, Giulia, additional, Finnerup, Nanna B., additional, Garcia‐Larrea, Luis, additional, Hanafi, Ibrahem, additional, Haroutounian, Simon, additional, Karlsson, Pall, additional, Rakusa, Martin, additional, Rice, Andrew S. C., additional, Sachau, Juliane, additional, Smith, Blair H., additional, Sommer, Claudia, additional, Tölle, Thomas, additional, Valls‐Solé, Josep, additional, and Veluchamy, Abirami, additional

Published
2023
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21. Paradoxical heat sensation as a manifestation of thermal hypesthesia: a study of 1090 patients with lesions of the somatosensory system.

Author

Vollert, Jan, Fardo, Francesca, Attal, Nadine, Baron, Ralf, Bouhassira, Didier, Enax-Krumova, Elena K., Freynhagen, Rainer, Hansson, Per, Jensen, Troels S., Kersebaum, Dilara, Maiern, Christoph, Pogatzki-Zahn, Esther, Rice, Andrew S. C., Sachau, Juliane, Schaldemose, Ellen L., Segerdahl, Märta, Sendel, Manon, Tölle, Thomas R., Finnerup, Nanna B., and Treede, Rolf-Detlef

Published
2024
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25. Veränderungen hypothalamischer Konnektivitäten mittels fMRT bei Migränepatienten im interiktalen und iktalen Erkrankungsintervall

Author

Tölle, Thomas R. (Prof. Dr. Dr.), Tölle, Thomas R. (Prof. Dr. Dr.);Kirschke, Jan St. (Prof. Dr.), Rehm, Mathias Günther, Tölle, Thomas R. (Prof. Dr. Dr.), Tölle, Thomas R. (Prof. Dr. Dr.);Kirschke, Jan St. (Prof. Dr.), and Rehm, Mathias Günther

Abstract

In dieser Dissertation wurde mittels funktioneller Magnetresonanztomographie die funktionelle Konnektivität des Hypothalamus bei 12 Migränepatienten über einen gesamten Migränezyklus untersucht. Es konnte eine zyklische Veränderung der Konnektivität zwischen Hypothalamus und anderen limbischen Regionen mit einem Maximum unmittelbar vor der Migräneattacke gezeigt werden. Hinsichtlich klinischer Charakteristika zeigte sich die Erkrankungsdauer (in Jahren) als modulierender Faktor der hypothalamischen Konnektivität., The present thesis investigates the migraine-related functional connectivity of the hypothalamus. Using functional magnetic resonance imaging, 12 migraineurs were tested throughout an entire migraine cycle. We determined a cyclic effect for the connectivity between hypothalamus and limbic circuits with a climax immediately before a migraine attack. Regarding clinical characteristics, we identified disease duration (in years) as a modulating factor of hypothalamic connectivity.

Published
2022

26. Can self-reported pain characteristics and bedside test be used for the assessment of pain mechanisms? An analysis of results of neuropathic pain questionnaires and quantitative sensory testing

Author

Gierthmühlen, Janne, Schneider, Ulrike, Seemann, Martina, Freitag-Wolf, Sandra, Maihöfner, Christian, Enax-Krumova, Elena K., Azad, Shahnaz-C., Üçeyler, Nurcan, Birklein, Frank, Maier, Christoph, Tölle, Thomas, Treede, Rolf-Detlef, and Baron, Ralf

Published
2019
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27. Germany

Author

Tölle, Thomas, primary, Schäfer, Michael, additional, and Isenberg, Thomas, additional

Published
2018
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30. Digitale Behandlung von unspezifischem Rückenschmerz – klinische und gesundheitsökonomische Ergebnisse des Rise-uP Trials

Author

Priebe, Janosch A., Kerkemeyer, Linda, Haas, Katharina K., Thoma, Reinhard, Jedamzik, Siegfried, Reichmann, Jan, Sundmacher, Leonie, Amelung, Volker, and Tölle, Thomas R.

Subjects
Rückenschmerz, Medicine and health, Digitale Medizin, DiGA, Schmerztherapie
Abstract

Fragestellung: Die Behandlung von unspezifischem Rückenschmerz erfolgt oft ohne Berücksichtigung der Leitlinien. Das wiederum führt dazu, dass 65% der Patienten mit akutem oder subakutem Rückenschmerz nach einem Jahr noch Beschwerden berichten. Im Rahmen des Cluster-randomisierten [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Published
2022
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32. Neuroimaging

Author

Pfab, Florian, Valet, Michael, Tölle, Thomas, Behrendt, Heidrun, Ring, Johannes, Darsow, Ulf, Misery, Laurent, editor, and Ständer, Sonja, editor

Published
2010
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37. Autorenverzeichnis

Author

Klingelhöfer, Jürgen, primary, Berthele, Achim, additional, Berrouschot, Jörg, additional, Bischoff, Christian, additional, Deschauer, Marcus, additional, Etgen, Thorleif, additional, Gregor, Olaf, additional, Hamer, Hajo, additional, Hau, Peter, additional, Klaus, Daniela, additional, Köhler, Wolfgang, additional, Lezaic, Vesna, additional, Näher-Noé, Martina, additional, Rege, Susan, additional, Sander, Dirk, additional, Schalke, Berthold, additional, Scheidhauer, Sabine, additional, Sprenger, Till, additional, Storch, Alexander, additional, Tölle, Thomas R., additional, and Spranger, Matthias, additional

Published
2017
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39. Schmerz

Author

Berthele, Achim, primary and Tölle, Thomas R., additional

Published
2017
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41. Schmerz

Author

Tölle, Thomas, Flor, Herta, Förstl, Hans, editor, Hautzinger, Martin, editor, and Roth, Gerhard, editor

Published
2006
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43. Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus

Author

Backonja, Miroslav “Misha”, Attal, Nadine, Baron, Ralf, Bouhassira, Didier, Drangholt, Mark, Dyck, Peter J., Edwards, Robert R., Freeman, Roy, Gracely, Richard, Haanpaa, Maija H., Hansson, Per, Hatem, Samar M., Krumova, Elena K., Jensen, Troels S., Maier, Christoph, Mick, Gerard, Rice, Andrew S., Rolke, Roman, Treede, Rolf-Detlef, Serra, Jordi, Toelle, Thomas, Tugnoli, Valeri, Walk, David, Walalce, Mark S., Ware, Mark, Yarnitsky, David, and Ziegler, Dan

Published
2013
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45. Verbesserung der Diagnose von Schmerzen im unteren Rückenbereich und Bewegungsleistungsfähigkeit bei gesunden Probanden und Patienten mit chronischen Schmerzen - Ergebnisse einer Pilotstudie

Author

Tölle, Thomas R. (Prof. Dr. Dr.), Tölle, Thomas R. (Prof. Dr. Dr.);von Eisenhart-Rothe, Rüdiger (Prof. Dr.), Fahrner, Maren Dorothee, Tölle, Thomas R. (Prof. Dr. Dr.), Tölle, Thomas R. (Prof. Dr. Dr.);von Eisenhart-Rothe, Rüdiger (Prof. Dr.), and Fahrner, Maren Dorothee

Abstract

In dieser Pilotstudie zur Verbesserung der Diagnose von Schmerzen im unteren Rückenbereich wird mit dem SpineSensor-System der OsteoDynamiX GmbH ein auf biegbaren Lichtwellenleitern beruhendes alternatives optisch-physikalisches-Messsystem für die Bewegungsfunktionen in Form von Umfang, Geschwindigkeit und Qualität im Vergleich bei gesunden Probanden und Patienten mit chronischen Schmerzen untersucht und die Ergebnisse vorgestellt., In this pilot study about the improvement of diagnosing dorsal pain in the lower back the OsteoDynamiX GmbH's SpineSensor system is examined as an alternative opto-physical measurement system based on flexible fiber optics for range, velocity, and quality of motion. The presentation of results includes a comparison to healthy volunteers and patients with chronic pain.

Published
2020

46. Veränderungen hypothalamischer Konnektivitäten mittels fMRT bei Migränepatienten im interiktalen und iktalen Erkrankungsintervall

Author

Kirschke, Jan St. (Prof. Dr.), Tölle, Thomas R. (Prof. Dr. Dr.), Rehm, Mathias Günther, Kirschke, Jan St. (Prof. Dr.), Tölle, Thomas R. (Prof. Dr. Dr.), and Rehm, Mathias Günther

Abstract

In dieser Dissertation wurde mittels funktioneller Magnetresonanztomographie die funktionelle Konnektivität des Hypothalamus bei 12 Migränepatienten über einen gesamten Migränezyklus untersucht. Es konnte eine zyklische Veränderung der Konnektivität zwischen Hypothalamus und anderen limbischen Regionen mit einem Maximum unmittelbar vor der Migräneattacke gezeigt werden. Hinsichtlich klinischer Charakteristika zeigte sich die Erkrankungsdauer (in Jahren) als modulierender Faktor der hypothalamischen Konnektivität., The present thesis investigates the migraine-related functional connectivity of the hypothalamus. Using functional magnetic resonance imaging, 12 migraineurs were tested throughout an entire migraine cycle. We determined a cyclic effect for the connectivity between hypothalamus and limbic circuits with a climax immediately before a migraine attack. Regarding clinical characteristics, we identified disease duration (in years) as a modulating factor of hypothalamic connectivity.

Published
2022

47. Shared Decision Making bei akutpsychiatrischen Patienten mit Störungen aus dem schizophrenen Formenkreis

Author

Hamann, Johannes (Prof. Dr.), Tölle, Thomas R. (Prof. Dr. Dr.), Becher, Stefanie Christina, Hamann, Johannes (Prof. Dr.), Tölle, Thomas R. (Prof. Dr. Dr.), and Becher, Stefanie Christina

Abstract

Diese Arbeit basiert auf qualitativen Daten der SDM-PLUS-Studie und untersucht das Maß an angewandtem SDM bei akut erkrankten Patienten mit Diagnosen aus dem schizophrenen Formenkreis während der stationären Behandlung in geschlossenen Stationen. Ziel ist, Erkenntnisse über erlebte behindernde und erleichternde Faktoren bzgl. SDM im Kontext einer vorigen erfolgreichen SDM-Intervention zu gewinnen. In den Ergebnissen wird deutlich, dass SDM auch unter schwierigen Bedingungen oftmals möglich ist., This paper is based on qualitative findings of the SDM PLUS trial whose purpose was to examine the amount of SDM applied with acutely ill inpatients with schizophrenia in closed wards and to seek out the perceived barriers and facilitators of SDM in said setting. Interviews were conducted with patients and their respective caregivers and then analysed using qualitative content analysis with a mixed methods approach. The results show that SDM is often possible, despite adverse circumstances.

Published
2022

49. Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles

Author

Baron, Ralf, Maier, Christoph, Attal, Nadine, Binder, Andreas, Bouhassira, Didier, Cruccu, Giorgio, Finnerup, Nanna B., Haanpää, Maija, Hansson, Per, Hüllemann, Philipp, Jensen, Troels S., Freynhagen, Rainer, Kennedy, Jeffrey D., Magerl, Walter, Mainka, Tina, Reimer, Maren, Rice, Andrew S.C., Segerdahl, Märta, Serra, Jordi, Sindrup, Sören, Sommer, Claudia, Tölle, Thomas, Vollert, Jan, and Treede, Rolf-Detlef

Published
2017
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