Difference between revisions of "7° Klinischer Fall: Hirnstammneoplasie bei orofazialen Schmerzen"

7° Klinischer Fall: Hirnstammneoplasie bei orofazialen Schmerzen (view source)

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 =====Antagonisten=====
+Antagonisten blockieren die Aktivität von TRPV1 und reduzieren dadurch den Schmerz. Identifizierte Antagonisten umfassen [[wikipedia:Receptor_antagonist#Competitive|den kompetitiven Antagonisten Capsazepin und den nicht-kompetitiven Antagonisten Rutheniumrot]]. Diese Wirkstoffe könnten von Nutzen sein, wenn sie systematisch angewendet werden.<ref>Khairatkar-Joshi N, Szallasi A (January 2009). "TRPV1 antagonists: the challenges for therapeutic targeting". ''Trends in Molecular Medicine''. '''15''' (1): 14–22. doi:10.1016/j.molmed.2008.11.004. <nowiki>PMID 19097938</nowiki>.</ref> TRPV1-Antagonisten haben Wirksamkeit gezeigt bei der Reduzierung von Nozizeption aus entzündlichen und neuropathischen Schmerzmodellen bei Ratten.<ref>Jhaveri MD, Elmes SJ, Kendall DA, Chapman V (July 2005). "Inhibition of peripheral vanilloid TRPV1 receptors reduces noxious heat-evoked responses of dorsal horn neurons in naïve, carrageenan-inflamed and neuropathic rats". ''The European Journal of Neuroscience''. '''22''' (2): 361–370. doi:10.1111/j.1460-9568.2005.04227.x. <nowiki>PMID 16045489</nowiki>. S2CID 24664751.</ref> Dies liefert Hinweise darauf, dass TRPV1 der einzige Rezeptor für [[wikipedia:Capsaicin|Capsaicin ist]].<ref>Story GM, Crus-Orengo L (2008). "Feel the Burn". ''American Scientist''. '''95''' (4): 326–333. doi:10.1511/2007.66.326. ISSN 0003-0996. Archived from the original on January 19, 2008.</ref> Bei Menschen könnten Medikamente, die auf TRPV1-Rezeptoren abzielen, zur Behandlung neuropathischer Schmerzen im Zusammenhang mit Multipler Sklerose, Chemotherapie oder Amputation sowie Schmerzen im Zusammenhang mit der entzündlichen Reaktion von geschädigtem Gewebe, wie bei Osteoarthritis, verwendet werden.<ref>Gunthorpe MJ, Szallasi A (2008). "Peripheral TRPV1 receptors as targets for drug development: new molecules and mechanisms". ''Current Pharmaceutical Design''. '''14''' (1): 32–41. doi:10.2174/138161208783330754. <nowiki>PMID 18220816</nowiki>.</ref>
-Antagonists block the ''activity of TRPV1'', thereby reducing pain. Antagonists identified include the [[wikipedia:Receptor_antagonist#Competitive|competitive antagonist capsazepine and the non-competitive antagonist]] [[wikipedia:Ruthenium_red|ruthenium red]]. These agents could be beneficial if applied systematically.<ref>Khairatkar-Joshi N, Szallasi A (January 2009). "TRPV1 antagonists: the challenges for therapeutic targeting". ''Trends in Molecular Medicine''. '''15''' (1): 14–22. doi:10.1016/j.molmed.2008.11.004. <nowiki>PMID 19097938</nowiki>.</ref> TRPV1 antagonists have shown efficacy in reducing nociception from inflammatory and neuropathic pain models in rats.<ref>Jhaveri MD, Elmes SJ, Kendall DA, Chapman V (July 2005). "Inhibition of peripheral vanilloid TRPV1 receptors reduces noxious heat-evoked responses of dorsal horn neurons in naïve, carrageenan-inflamed and neuropathic rats". ''The European Journal of Neuroscience''. '''22''' (2): 361–370. doi:10.1111/j.1460-9568.2005.04227.x. <nowiki>PMID 16045489</nowiki>. S2CID 24664751.</ref> This provides evidence that TRPV1 is the sole receptor for [[wikipedia:Capsaicin|capsaicin]].<ref>Story GM, Crus-Orengo L (2008). "Feel the Burn". ''American Scientist''. '''95''' (4): 326–333. doi:10.1511/2007.66.326. ISSN 0003-0996. Archived from the original on January 19, 2008.</ref> In humans, drugs that target TRPV1 receptors could be used to treat neuropathic pain associated with multiple sclerosis, chemotherapy, or amputation, as well as pain associated with the inflammatory response of damaged tissue, such as in osteoarthritis.<ref>Gunthorpe MJ, Szallasi A (2008). "Peripheral TRPV1 receptors as targets for drug development: new molecules and mechanisms". ''Current Pharmaceutical Design''. '''14''' (1): 32–41. doi:10.2174/138161208783330754. <nowiki>PMID 18220816</nowiki>.</ref>
+=====Agonisten=====
+TRPV1 wird von verschiedenen Agonisten natürlichen Ursprungs aktiviert.<ref>Boonen, Brett; Startek, Justyna B.; Talavera, Karel (2016-01-01). Chemical Activation of Sensory TRP Channels. Topics in Medicinal Chemistry. Springer Berlin Heidelberg. pp. 1–41. [1]doi:10.1007/7355_2015_98.</ref> Agonisten wie Capsaicin und Resiniferatoxin aktivieren TRPV1 und führen nach langanhaltender Anwendung zu einer Verringerung der TRPV1-Aktivität (Desensibilisierung), was zu einer Schmerzlinderung durch die anschließende Verringerung der TRPV1-vermittelten Freisetzung von entzündlichen Molekülen bei Exposition gegenüber schädlichen Reizen führt.
-=====Agonists=====
+Eine interessante Studie der Tominaga-Gruppe erweitert die Liste der TRPV1-Interaktionen auch auf Anoctamin 1 (ANO 1), auch bekannt als Transmembranmitglied 16A (TMEM16A),<ref name=":2">Yasunori Takayama, Daisuke Uta, Hidemasa Furue, and Makoto Tominaga. Pain-enhancing mechanism through interaction between TRPV1 and anoctamin 1 in sensory neurons. Proc Natl Acad Sci 2015; 21; 112(16): 5213-5218. doi: 10.1073/pnas.1421507112. Epub 2015 Apr 6.</ref> einen Chloridkanal, der normalerweise durch Ca<sup>2+</sup> aktiviert wird. Die Autoren zeigen tatsächlich, dass, wenn TRPV1 mit dem ANO1-Kanal interagiert, dies den Ausstrom von Chlorid vermittelt und Depolarisation auslöst (nach Stimulation durch Capsaicin) mit erhöhter Erregbarkeit des Nociceptors. Tominaga betont einen klaren strukturellen und funktionellen Crosstalk zwischen TRPV1 und ANO1, der bei der algogenen Wirkung von Capsaicin eingreift.
-TRPV1 is activated by several agonists of natural origin.<ref>Boonen, Brett; Startek, Justyna B.; Talavera, Karel (2016-01-01). Chemical Activation of Sensory TRP Channels. Topics in Medicinal Chemistry. Springer Berlin Heidelberg. pp. 1–41. [1]doi:10.1007/7355_2015_98.</ref> Agonists such as capsaicin and resiniferatoxin activate TRPV1 and, after prolonged application, cause the decrease of TRPV1 activity (desensitization), leading to pain relief through the subsequent decrease of the TRPV1-mediated release of inflammatory molecules upon exposure to noxious stimuli.
-An interesting study by the Tominaga group extends the list of TRPV1 interactions also to Anoctamin 1 (ANO 1) also known as Transmembrane member 16A (TMEM16A) a chloride channel which is usually activated by Ca2+. The authors demonstrate, in fact, that when TRPV1 interacts with the ANO1 channel it mediates the efflux of Chloride evoking depolarization (after stimulation by capsaicin) with increased excitability of the nociceptor. Tominaga highlighted a clear structural and functional crosstalk between TRPV1 and ANO1, which intervenes in the algogenic action of capsaicin.
+Diese Ergebnisse zeigen die Bedeutung der Chlorid-Homöostase für die Regulation der Erregbarkeit der neuronalen DRGs, d.h. der dorsalen Wurzelganglien, und offensichtlich der trigeminalen somatosensorischen Kerne und des Schmerzphänomens als Ganzes auf; eine der neuen Ansätze, um die schmerzhafte Hypersensitivität und die neurogene Entzündung zu mildern.
-These results demonstrate the importance of chloride homeostasis in the regulation of the excitability of the neuronal DRGs, i.e. of the dorsal root ganglia and obviously of the trigeminal somatosensory nuclei and in the pain phenomenon as a whole; one of the new approaches, therefore, where to intervene to mitigate painful hypersensitivity and neurogenic inflammation.
+TRPV1 wird von mehreren Agonisten natürlichen Ursprungs aktiviert. Agonisten wie Capsaicin und Resiniferatoxin aktivieren TRPV1 und führen nach langanhaltender Anwendung zu einer Verringerung der TRPV1-Aktivität (Desensibilisierung), was zu einer Schmerzlinderung durch die anschließende Verringerung der TRPV1-vermittelten Freisetzung von entzündlichen Molekülen nach Exposition gegenüber schädlichen Reizen führt.
-TRPV1 is activated by several agonists of natural origin. Agonists such as capsaicin and resiniferatoxin activate TRPV1 and, after prolonged application, cause the decrease of TRPV1 activity (desensitization), leading to pain relief through the subsequent decrease of TRPV1-mediated release of inflammatory molecules following administration. exposure to noxious stimuli.
-An interesting study by the Tominaga group extends the list of TRPV1 interactions also to [[wikipedia:ANO1|'''Anoctamin 1 (ANO 1)''']]  also known as Transmembrane member 16A (TMEM16A)<ref name=":2">Yasunori Takayama, Daisuke Uta, Hidemasa Furue, and Makoto Tominaga. Pain-enhancing mechanism through interaction between TRPV1 and anoctamin 1 in sensory neurons. Proc Natl Acad Sci 2015; 21; 112(16): 5213-5218. doi: 10.1073/pnas.1421507112. Epub 2015 Apr 6.</ref> a chloride channel which is usually activated by Ca2+. The authors demonstrate, in fact, that when TRPV1 interacts with the ANO1 channel it mediates the efflux of Chloride evoking depolarization (after stimulation by capsaicin) with increased excitability of the nociceptor. Tominaga<ref name=":2" /> highlighted a clear structural and functional crosstalk between TRPV1 and ANO1, which intervenes in the algogenic action of capsaicin.
-These results demonstrate the importance of chloride homeostasis in the regulation of the excitability of the neuronal DRGs, i.e. of the dorsal root ganglia and obviously of the trigeminal somatosensory nuclei and in the pain phenomenon as a whole; one of the new approaches, therefore, where to intervene to mitigate painful hypersensitivity and neurogenic inflammation.
+Eine interessante Studie der Tominaga-Gruppe erweitert die Liste der TRPV1-Interaktionen auch auf [[wikipedia:ANO1|'''Anoctamin 1 (ANO 1)''']] , auch bekannt als Transmembranmitglied 16A (TMEM16A),<ref name=":2" /> einen Chloridkanal, der normalerweise durch Ca<sup>2+</sup> aktiviert wird. Die Autoren zeigen tatsächlich, dass, wenn TRPV1 mit dem ANO1-Kanal interagiert, dies den Ausstrom von Chlorid vermittelt und Depolarisation auslöst (nach Stimulation durch Capsaicin) mit erhöhter Erregbarkeit des Nociceptors. Tominaga<ref name=":2" /> betont einen klaren strukturellen und funktionellen Crosstalk zwischen TRPV1 und ANO1, der bei der algogenen Wirkung von Capsaicin eingreift.
-{{Q2|Why, then, did the capsaicin taken in the food reported by the patient generate an exacerbation of pain?|....for chronic damage to the brainstem nerve fibers with consequent alteration of the neuro-immune homeostasis and contextual paradoxical effect of the analgesic action of capsaicin.}}In these cases, as stated in other chapters, we are dealing with an epistemological profile in which the basic knowledge, what we have called <math>KB</math> (Knowledge Base) corresponds to a temporal limit of scientific information and consequently serious  difficulties of differential diagnosis. We had to wait 12 years to reach an ezipathogenetic conclusion overwritten from 1995, a period in which the patient 'Capsaicin' was being treated, to 2007 in which a research gave the elements to suspect the presence of an organic neurological damage with manifestations of pain and burning mouth.<ref>Z Yilmaz, T Renton, Y Yiangou, J Zakrzewska, I P Chessell, C Bountra, P Anand. Burning mouth syndrome as a trigeminal small fibre neuropathy: Increased heat and capsaicin receptor TRPV1 in nerve fibres correlates with pain score. J Clin Neurosci. 2007 Sep;14(9):864-71. doi: 10.1016/j.jocn.2006.09.002. Epub 2007 Jun 19.
+Diese Ergebnisse zeigen die Bedeutung der Chlorid-Homöostase für die Regulation der Erregbarkeit der neuronalen DRGs, d.h. der dorsalen Wurzelganglien, und offensichtlich der trigeminalen somatosensorischen Kerne und des Schmerzphänomens als Ganzes auf; eine der neuen Ansätze, um die schmerzhafte Hypersensitivität und die neurogene Entzündung zu mildern.
-</ref> Burning mouth syndrome (BMS) is often an idiopathic, chronic intractable pain condition, affecting 1.5-5.5% of middle-aged and older women. We investigated heat and capsaicin receptor TRPV1, and its regulatory nerve growth factor (NGF), in BMS. BMS patients (n=10) and controls (n=10) were evaluated for baseline and post-topical capsaicin pain scores, and their tongue biopsies were immunostained for TRPV1, NGF, and neurofilament structural nerve markers and periphery. Nerve fibers penetrating the epithelium were less abundant in the BMS (p<0.0001), indicating ''small fiber neuropathy''. TRPV1-positive fibers were overall significantly increased in BMS (p=0.0011), as were NGF fibers (p<0.0001) and NGF staining of basal epithelial cells (p<0.0147). There was a significant correlation between baseline pain score and TRPV1 (p=0.0143) and NGF (p=0.0252) fibers. A significant correlation was observed between baseline and post-capsaicin pain (p=0.0006).
+{{Q2|Warum hat das von dem Patienten eingenommene Capsaicin in der Nahrung eine Verschlimmerung des Schmerzes verursacht?|... aufgrund des chronischen Schadens an den Nervenfasern des Hirnstamms mit anschließender Veränderung der neuroimmunen Homöostase und des paradoxen kontextuellen Effekts der analgetischen Wirkung von Capsaicin.}}In these cases, as stated in other chapters, we are dealing with an epistemological profile in which the basic knowledge, what we have called <math>KB</math> (Knowledge Base) corresponds to a temporal limit of scientific information and consequently serious  difficulties of differential diagnosis. We had to wait 12 years to reach an ezipathogenetic conclusion overwritten from 1995, a period in which the patient 'Capsaicin' was being treated, to 2007 in which a research gave the elements to suspect the presence of an organic neurological damage with manifestations of pain and burning mouth. Burning mouth syndrome (BMS) is often an idiopathic, chronic intractable pain condition, affecting 1.5-5.5% of middle-aged and older women. We investigated heat and capsaicin receptor TRPV1, and its regulatory nerve growth factor (NGF), in BMS. BMS patients (n=10) and controls (n=10) were evaluated for baseline and post-topical capsaicin pain scores, and their tongue biopsies were immunostained for TRPV1, NGF, and neurofilament structural nerve markers and periphery. Nerve fibers penetrating the epithelium were less abundant in the BMS (p<0.0001), indicating ''small fiber neuropathy''. TRPV1-positive fibers were overall significantly increased in BMS (p=0.0011), as were NGF fibers (p<0.0001) and NGF staining of basal epithelial cells (p<0.0147). There was a significant correlation between baseline pain score and TRPV1 (p=0.0143) and NGF (p=0.0252) fibers. A significant correlation was observed between baseline and post-capsaicin pain (p=0.0006).
-{{Q2|We are sure we know everything|}}{{bib}}
+{{Q2|Wir sind sicher, dass wir alles wissen.|}}{{bib}}