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      Efecto analgésico del parche de capsaicina al 8 % a través del receptor vaniloide TRPV-1, en un paciente con enfermedad de Parkinson y dolor neuropático localizado Translated title: Analgesic effect of the capsaicin 8 % patch through the TRPV-1 receptor in a case of Parkinson disease with located neuropathic pain

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          Abstract

          RESUMEN La enfermedad de Parkinson es un trastorno neurodegenerativo que comporta la alteración de las vías dopaminérgicas de los ganglios basales. El dolor que puede acompañar a la enfermedad de Parkinson se debe a mecanismos de depleción de las neuronas dopaminérgicas de la sustancia negra. Su etiología puede ser de origen central o periférico. Por ello, la aparición de dolor supone un reto clínico para distinguir entre ambos tipos y aplicar distintos tratamientos específicos. Se ha descrito que el receptor vaniloide TRPV-1 de los astrocitos previene la degeneración progresiva de neuronas dopaminérgicas de la enfermedad de Parkinson y se asocia con una mejoría funcional y del dolor. Por otro lado, sabemos que la capsaicina es un potente activador exógeno del receptor vaniloide. Presentamos el caso de una mujer de 71 años con enfermedad de Parkinson de larga evolución, en tratamiento con estimulación cerebral profunda y fármacos agonistas de la dopamina. La paciente acudió a nuestra Unidad por la presencia de dolor localizado en la región superoexterna de la rodilla izquierda, de carácter continuo y sin respuesta a fármacos utilizados para tratar el dolor nociceptivo. Una vez completada la anamnesis y valorada la exploración física y pruebas complementarias, se excluyó la causa orgánica. Se aplicó la escala DN4 para el dolor neuropático, obteniéndose una puntuación de 5 puntos. Se etiquetó como dolor neuropático periférico localizado. Se aplicó un parche de capsaicina 179 mg sobre la región dolorosa de la rodilla, y la paciente fue revisada en consulta a los 7, 30 y 90 días, obteniéndose un alivio del dolor desde la semana 1. En la última revisión a los 90 días, persiste la mejoría clínica. La capsaicina tópica de alta concentración se comportó como un fármaco agonista altamente selectivo del receptor vaniloide TRPV-1, ya que las neuronas sensitivas de la piel expresan dicho receptor. Por otro lado, el parche de capsaicina 8 % permitió tratar a la paciente evitando posibles interacciones farmacológicas con su medicación habitual. En conclusión, la capsaicina tópica de alta concentración se mostró eficaz y segura en el tratamiento del dolor neuropático localizado en una paciente con enfermedad de Parkinson y difícil manejo.

          Translated abstract

          ABSTRACT Nowadays differentiation between central and peripheral origin in Parkinson's disease pain is considered as a clinical challenge. We present a long evolution Parkinson's disease case of a 71 years old woman. Treatment undergone by the patient consists in deep brain stimulation (DBS), drugs dopamine agonist, monoamine oxidase inhibitor-B (MAO-B) and catechol-O-methyltransferase inhibitor (COMT).The patient was referred to the pain unit due to an outbreak of continuous pain in the upper outer region of the left knee and no response to pharmacological nocioceptive pain treatment. The patient was diagnosed with neuropathic pain after reviewing her clinical history, the physical examination and application of the DN4 scale. The chosen treatment was the application of a 179 mg capsaicin patch over the region where she was experiencing the pain and it resulted in an improvement from week one which still persisting twelve weeks later. Treatment with capsaicin patch was selected with the aim of avoid possible drugs interactions with her treatment. As a conclusion, the high topical concentration of capsaicin has been found to be effective and safe in a patient with complicated treatment (DBS plus usual treatment).

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          TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice

          The capsaicin receptor TRPV1 has been widely characterized in the sensory system as a key component of pain and inflammation. A large amount of evidence shows that TRPV1 is also functional in the brain although its role is still debated. Here we report that TRPV1 is highly expressed in microglial cells rather than neurons of the anterior cingulate cortex and other brain areas. We found that stimulation of microglial TRPV1 controls cortical microglia activation per se and indirectly enhances glutamatergic transmission in neurons by promoting extracellular microglial microvesicles shedding. Conversely, in the cortex of mice suffering from neuropathic pain, TRPV1 is also present in neurons affecting their intrinsic electrical properties and synaptic strength. Altogether, these findings identify brain TRPV1 as potential detector of harmful stimuli and a key player of microglia to neuron communication.
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            Validity and reliability of the Spanish version of the DN4 (Douleur Neuropathique 4 questions) questionnaire for differential diagnosis of pain syndromes associated to a neuropathic or somatic component

            Background This study assesses the validity and reliability of the Spanish version of DN4 questionnaire as a tool for differential diagnosis of pain syndromes associated to a neuropathic (NP) or somatic component (non-neuropathic pain, NNP). Methods A study was conducted consisting of two phases: cultural adaptation into the Spanish language by means of conceptual equivalence, including forward and backward translations in duplicate and cognitive debriefing, and testing of psychometric properties in patients with NP (peripheral, central and mixed) and NNP. The analysis of psychometric properties included reliability (internal consistency, inter-rater agreement and test-retest reliability) and validity (ROC curve analysis, agreement with the reference diagnosis and determination of sensitivity, specificity, and positive and negative predictive values in different subsamples according to type of NP). Results A sample of 164 subjects (99 women, 60.4%; age: 60.4 ± 16.0 years), 94 (57.3%) with NP (36 with peripheral, 32 with central, and 26 with mixed pain) and 70 with NNP was enrolled. The questionnaire was reliable [Cronbach's alpha coefficient: 0.71, inter-rater agreement coefficient: 0.80 (0.71–0.89), and test-retest intra-class correlation coefficient: 0.95 (0.92–0.97)] and valid for a cut-off value ≥ 4 points, which was the best value to discriminate between NP and NNP subjects. Discussion This study, representing the first validation of the DN4 questionnaire into another language different than the original, not only supported its high discriminatory value for identification of neuropathic pain, but also provided supplemental psychometric validation (i.e. test-retest reliability, influence of educational level and pain intensity) and showed its validity in mixed pain syndromes.
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              The effect of deep brain stimulation on the non-motor symptoms of Parkinson’s disease: a critical review of the current evidence

              The benefit of deep brain stimulation (DBS) in controlling the motor symptoms of Parkinson’s disease is well established, however, the impact on the non-motor symptoms (NMS) remains to be elucidated, although the growing investigative efforts are promising. This article reviews the reported data and considers the level of evidence available with regard to the effect of DBS on NMS total burden and on the cognitive, neuropsychiatric, sleep, pain, dysautonomic, and weight domains. Multiple case series suggest that DBS improves the burden of NMS by reducing prevalence, intensity, and non-motor fluctuations. There is level I evidence on the effect of DBS on cognition and mood. Slight cognitive decline has been reported in most class I studies, although the functional effect is probably minimal. Two randomized prospective studies reported no change in depression while improvement of anxiety has been reported by a class I trial. Prospective cohort studies point to improvement of hyperdopaminergic behaviors, such as impulse control disorders, while others report that hypodopaminergic states, like apathy, can appear after DBS. There is only class III evidence supporting the benefit of DBS on other NMS such as nocturnal sleep, pain, dysautonomia (urinary, gastrointestinal, cardiovascular, and sweating), and weight loss. Although preliminary results are promising, randomized prospectively controlled trials with NMS as primary end points are necessary to further explore the effect of DBS on these often invalidating symptoms and offer conclusions about efficacy.
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                Author and article information

                Journal
                dolor
                Revista de la Sociedad Española del Dolor
                Rev. Soc. Esp. Dolor
                Inspira Network Group, S.L (Madrid, Madrid, Spain )
                1134-8046
                June 2020
                : 27
                : 3
                : 216-220
                Affiliations
                [2] León orgnameComplejo Asistencial Universitario de León orgdiv1Servicio de Anestesiología y Reanimación España
                [1] León orgnameComplejo Asistencial Universitario de León orgdiv1Servicio de Anestesiología y Reanimación orgdiv2Unidad de Dolor España
                Article
                S1134-80462020000300216 S1134-8046(20)02700300216
                10.20986/resed.2020.3786/2019
                4c93ba1e-5f02-411e-a4a7-01ab4a64df0b

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 13 January 2020
                : 28 November 2019
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 12, Pages: 5
                Product

                SciELO Spain

                Categories
                Notas Clínicas

                Parkinson,TRPV-1 receptor,capsaicin,capsaicina,receptor TRPV-1

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