Biochemical characterization of two trimers of the bacterial cell division protein (FtsZ) from E. coli / CARACTERIZACIÓN BIOQUÍMICA DE DOS TRÍMEROS DE LA PROTEÍNA DE LA DIVISIÓN CELULAR BACTERIANA (FtsZ) DE E. coli.

FtsZ is a bacterial divisome protein responsible for Z-ring formation in cytokinesis. Characterization of Escherichia coli FtsZ protein oligomers (EcFtsZ) in native conditions is defiance because the protein is found as a multi-oligomer in self-association-dissociation equilibrium. We characterize the trimeric state of EcFtsZ through native PAGE, gel filtration chromatography and sucrose gradient techniques combined with chemical cross-linking. The filtration results indicate that the EcFtsZ trimer has a molecular mass of 131 kDa and a filtration friction coefficient (Rs/Rmin) equal to 1.9, while the theoretical filtration friction coefficient (fn/f1) calculated for a linear trimer yielded a value equal to 1.8 very close to the experimental value. On the other side, formaldehyde-crosslinked EcFtsZ showed a band 128 kDa recognized by anti-FtsZ antibodies, and a sedimentation friction coefficient (Smax/S20,w) equal to 1.9, while the theoretical sedimentation friction coefficient (Sn/S1) calculated for a triangular trimer was equal to the experimental value. These results suggest that EcFtsZ has two homotrimeric structures (linear and triangular). Finally, we report the aggregation of EcFtsZ at micromolar concentrations of Capsaicin without GTP and Mg2+.

La FtsZ es una proteína del divisoma bacteriano responsable de la formación del anillo Z en la citocinesis. La caracterización de los oligómeros de la proteína FtsZ de Escherichia coli (EcFtsZ) en su estado nativo es un desafío porque la proteína se encuentra como un multioligómero en equilibrio de autoasociación-disociación. Nosotros caracterizamos el estado trimérico de la EcFtsZ a través de técnicas de PAGE nativo, cromatografía de filtración en gel y gradiente de sacarosa combinada con entrecruzamiento químico. Los resultados por filtración indican que el trímero de EcFtsZ tiene una masa molecular de 131 kDa y un coeficiente de fricción por filtración (Rs/Rmin) igual a 1.9, mientras que el coeficiente de fricción por filtración teórico (fn/f1) calculado para un trímero lineal arrojó un valor igual a 1.8 que está muy cercano al valor experimental. Por otro lado, la EcFtsZ entrecruzada con formaldehído presentó una banda de 128 kDa reconocida por anticuerpos anti-FtsZ y un coeficiente de fricción por sedimentación (Smax/S20,w) igual a 1.9, mientras que el coeficiente de fricción por sedimentación teórico (Sn/S1) calculado para un trímero triangular resultó igual a valor experimental. Estos resultados sugieren que la EcFtsZ tiene dos estructuras homotriméricas (lineal y triangular). Finalmente, reportamos la agregación de la EcFtsZ a concentraciones micromolares de Capsaicina sin GTP y Mg2+.

Síndrome de hiperémesis por cannabis: incidencia y tratamiento con capsaicina tópica / Cannabis hyperemesis syndrome: Incidence and treatment with topical capsaicin

Introducción: Existen pocos estudios en España acerca del síndrome de hiperémesis cannabinoide (SHC), así como sobre el uso de capsaicina tópica para su tratamiento.Métodos:Estudio retrospectivo de pacientes mayores de 14 años atendidos en un servicio de urgencias hospitalario durante 2018 y 2019 con diagnóstico de SHC con base en los siguientes criterios: cuadro clínico compatible, consumo de cannabis menor de 48h y test de cannabis en orina positivo. Se recogieron variables epidemiológicas, clínicas, tiempos asistenciales y tratamiento (incluyendo el uso de capsaicina tópica al 0,075%).Resultados:Se estudiaron 59 asistencias de 29 pacientes (4,4 casos/10.000 visitas, IC 95% 2,8-4,7). Un 50% volvieron a urgencias por SHC, diferenciándose estos solo en más consumo de tabaco (p=0,01) y cocaína (p=0,031). En un 74,6% de las visitas se utilizó capsaicina. El tiempo medio de resolución de los vómitos tras su aplicación fue de 17,87min.Conclusiones:Aunque probablemente esté infradiagnosticado, el SHC presenta una incidencia baja en las urgencias en España, y con alta reincidencia de los pacientes. El uso de pomada de capsaicina es eficiente y seguro. (AU)

There are few studies in Spain on cannabinoid hyperemesis syndrome (CHS), as well as on the use of topical capsaicin as a treatment.Methods:Retrospective study of patients over 14 years of age seen in a hospital emergency department during 2018 and 2019 with a diagnosis of CHS based on the following criteria: compatible clinical picture, cannabis use less than 48h and positive urine cannabis test. Epidemiological and clinical variables, attendance times and treatment (including use of topical capsaicin 0.075%) were collected.Results:Fifty-nine attendances were studied, from 29 patients (4.4 cases/10,000 visits, 95% CI 2.8-4.7). Fifty per cent returned for CHS, differing only in more tobacco (P=.01) and cocaine (P=.031) use. Capsaicin was used in 74.6% of visits. The mean time to resolution of vomiting after application was 17.87min.Conclusions:Although probably underdiagnosed, CHS has a low incidence in the emergency department in Spain, with high patient recurrence. The use of capsaicin ointment is efficient and safe. (AU)

Aplicación y seguimiento del tratamiento del dolor neuropático periférico con capsaicina 179 mg realizado por enfermeras / Application and follow-up of the peripheral neuropathic pain treatment with capsaicin 179 mg conducted by nurses

Objetivo: evaluar la efectividad del tratamiento con parches de capsaicina 179 mg en personas con dolor neuropático periférico aplicado y en seguimiento realizado por enfermeras. Método: serie de casos longitudinal retrospectiva efectuada en la Unidad de Dolor del Hospital Universitario Son Llàtzer (Palma) entre 2018 y 2020. La población de estudio fue de 163 personas con ese tratamiento. Se llevó a cabo medición basal al mes, a los tres y a los seis meses. Se midieron sexo, edad, tiempo de evolución, aplicaciones realizadas, mejora en intensidad (NPRS: 0 a 10 puntos) y extensión del dolor, calidad de vida relacionada con la salud (EQ-5D-3L: 0 peor a 1 mejor), impresión de mejoría global del paciente (PGI-I: mejora; empeora o no mejora), uso de fármacos adyuvantes y efectos secundarios. Se llevó a cabo estadística descriptiva. Resultados: se incluyeron 133 pacientes con registros completos (= 57 años; = 30,2 meses de evolución; = 1,6 aplicaciones por persona). Se redujo la zona de dolor [Sí reduce (Mes 1: 67%; Mes 3: 41%; Mes 6: 20%)] y la intensidad del dolor pasó de = 7,35 a 6,32 al sexto mes. La calidad de vida fue superior a la media basal (0,37 sobre 1) en todas las mediciones. Mejoró la PGI [Mejora (Mes 1: 64,6%: Mes 3: 58,9%; Mes 6: 53,6 %)]. Disminuyó el uso de medicación adyuvante [Sí reduce (Mes 1: 28%; Mes 3: 30%; Mes 6: 67%)]. Los efectos adversos fueron dolor (78,9%), eritema (67,7%) y prurito (63,9%). Conclusión: el tratamiento aplicado por enfermeras fue eficaz y seguro. El seguimiento debe ser prolongado para detectar necesidades y cambios.(AU)

Objective: to evaluate the efficacy of the treatment with capsaicin 179mg patches applied and on follow-up by nurses in persons with peripheral neuropathic pain. Method: a longitudinal retrospective series of cases conducted at the Pain Unit of the Hospital Universitario Son Llàtzer between 2018 and 2020. The study population consisted of 196 persons with that treatment. Basal measurement was conducted at one month, at three and six months. The following were measured: gender, age, time of evolution, applications conducted, improvement in intensity (NPRS scale: 0 to 10 points) and extent of pain, health-related quality of life (EQ-5D-3L: 0=the worst to 1=the best), patient global impression of improvement (PGI-I: improvement, worsening or no improvement), use of adjuvant drugs and side effects. Descriptive statistics was applied. Results: 133 patients were included with complete records(= 57 years; = 30.2 months of evolution; = 1.6 applications per person). There was a reduction in the pain area [Reduced (Month 1: 67%; Month 3: 41%; Month 6: 20%)] and pain intensity moved from = 7.35 to 6.32 at month six. Quality of life was superior to the mean baseline (0.37 of 1) in all measurements. There was improvement in PGI [Improvement (Month 1: 64.6%: Month 3: 58.9%; Month 6: 53.6 %)]. There was a reduction in the use of adjuvant medication [Reduced (Month 1: 28%; Month 3: 30%; Month 6: 67%)]. The adverse effects were pain (78.9%), erythema (67.7%) and itching (63.9%). Conclusion: the treatment applied by nurses was effective and safe. There must be follow-up at long term in order to detect any needs and changes.(AU)

Uso de parches de capsaicina al 8 % para el tratamiento del dolor neuropático lumbar / Use of 8 % capsaicin patches for the treatment of lumbar neuropathic pain

Introducción: El dolor neuropático lumbar es una patología frecuente en la clínica diaria, con un tratamiento complejo, tanto farmacológico como intervencionista. Estos tratamientos podemos complementarlos con un parche transdérmico de capsaicina al 8 %. La capsaicina es agonista selectivo de los receptores TRPV1 (receptor transitorio vanilla de 1) cuya activación bloquea la liberación de sustancia P, muy implicada en el proceso de la inflamación. Objetivos: Valorar la utilidad del parche de capsaicina al 8 % como complemento en pacientes con dolor neuropático lumbar. Como objetivo secundario, valorar los efectos adversos del parche de capsaicina tanto en el momento de aplicación como a los 3 meses. Pacientes y métodos: Estudio retrospectivo, observacional y descriptivo, en el que se incluyeron 20 pacientes con dolor neuropático lumbar, tratados con parche de capsaicina al 8 % (Qutenza® como complemento al tratamiento habitual de esta patología. Se utilizaron 3 test para valorar el dolor: EVA (escala visual analógica del dolor), DN4 y LANSS para dolor neuropático. Los 3 test fueron pasados a los pacientes antes de la aplicación del parche y a los 3 meses de este. Resultados: Al inicio, el 95 % de los pacientes incluidos en el estudio presentaban dolor muy severo (EVA 8-9). A los 3 meses, el 85 % de los pacientes refieren dolor moderado (EVA 5-6). Con respecto al test DN4 observamos una disminución de los valores de algo más de 2 puntos. En el test LANSS encontramos una disminución de más de 5 puntos en estos 3 meses. La aplicación del parche no causó efectos secundarios significativos. Conclusiones: El parche de capsaicina al 8 % se ha mostrado eficaz y seguro como tratamiento complementario para el dolor neuropático lumbar.(AU)

Introduction: Lumbar neuropathic pain is a common pathology in daily clinical practice, with a complex treatment, both pharmacological and interventional. These treatments can be complemented with an 8 % capsaicin transdermal patch. Capsaicin is a selective agonist of TRPV1 receptors (transient receptor vanilla 1) whose activation blocks the release of substance P, which is heavily involved in the inflammatory process. Objectives: To assess the usefulness of the capsaicin 8 % patch as an adjunct in patients with lumbar neuropathic pain. As a secondary objective, to assess the adverse effects of the capsaicin patch both at the time of application and after 3 months. Patients and methods: Retrospective, observational and descriptive study, which included 20 patients with lumbar neuropathic pain, treated with capsaicin patch 8 % (Qutenza® as an adjunct to the usual treatment of this pathology. Three tests were used to assess pain: VAS (visual analogue pain scale), DN4 and LANSS for neuropathic pain. The 3 tests were administered to the patients before the application of the patch and 3 months after the patch was applied. Outcomes: At baseline, 95 % of patients included in the study had very severe pain (VAS 8-9). At 3 months, 85 % of patients reported moderate pain (VAS 5-6). With respect to the DN4 test, we observed a decrease in values of slightly more than 2 points. In the LANSS test we found a decrease of more than 5 points in these 3 months. The application of the patch did not cause significant side effects. Conclusions: The 8 % capsaicin patch has been shown to be effective and safe as an adjunctive treatment for lumbar neuropathic pain.(AU)

Cannabis hyperemesis syndrome: Incidence and treatment with topical capsaicin. / Síndrome de hiperémesis por cannabis: incidencia y tratamiento con capsaicina tópica.

There are few studies in Spain on cannabinoid hyperemesis syndrome (CHS), as well as on the use of topical capsaicin as a treatment. METHODS: Retrospective study of patients over 14 years of age seen in a hospital emergency department during 2018 and 2019 with a diagnosis of CHS based on the following criteria: compatible clinical picture, cannabis use less than 48h and positive urine cannabis test. Epidemiological and clinical variables, attendance times and treatment (including use of topical capsaicin 0.075%) were collected. RESULTS: Fifty-nine attendances were studied, from 29 patients (4.4 cases/10,000 visits, 95% CI 2.8-4.7). Fifty per cent returned for CHS, differing only in more tobacco (P=.01) and cocaine (P=.031) use. Capsaicin was used in 74.6% of visits. The mean time to resolution of vomiting after application was 17.87min. CONCLUSIONS: Although probably underdiagnosed, CHS has a low incidence in the emergency department in Spain, with high patient recurrence. The use of capsaicin ointment is efficient and safe.

Localized neuropathic pain.

Localized neuropathic pain (LNP) is of peripheral origin and is characterized by circumscribed areas of pain with abnormal skin sensitivity or spontaneous symptoms that are characteristic of neuropathic pain, e.g., burning pain. It should be noted that LNP is confined to a specific area no larger than a letter size sheet of paper. LNP accounts for 60 % of neuropathic pain syndromes. There is no single etiology of LNP. The diagnostic approach is similar to that for other neuropathic pain conditions. General diagnostic tools are used to assess clinical features. So far, there are no specific guidelines for the management of LNP; for this reason, guidelines for general neuropathic pain are used. Topical treatments are included as part of second-line strategies in the Canadian Pain Society guidelines. Despite the lack of guidelines, 5 % lidocaine patches and 8 % capsaicin patches have been proven effective in LNP models.

El dolor neuropático localizado (DNL) es de origen periférico y se caracteriza por áreas circunscritas de dolor con sensibilidad anormal de la piel o síntomas espontáneos característicos de dolor neuropático, por ejemplo, dolor urente. Se debe resaltar que el DNL está confinado a un área específica no mayor a una hoja de papel tamaño carta. El DNL representa 60 % de las condiciones de dolor neuropático. No existe una única etiología. El abordaje diagnóstico es similar al de otros síndromes dolorosos neuropáticos. Se utilizan herramientas diagnósticas generales para evaluar las características clínicas. En la actualidad no existen guías específicas de manejo del DNL, por lo que se utilizan las guías para dolor neuropático en general. En las guías de la Sociedad Canadiense de Dolor se incluyen los tratamientos tópicos como parte de las estrategias de segunda línea. Pese a la falta de guías, los parches de lidocaína a 5 % y los parches de capsaicina a 8 % han demostrado ser efectivos en modelos de DNL.

Dolor neuropático localizado / Localized neuropathic pain

Resumen El dolor neuropático localizado (DNL) es de origen periférico y se caracteriza por áreas circunscritas de dolor con sensibilidad anormal de la piel o síntomas espontáneos característicos de dolor neuropático, por ejemplo, dolor urente. Se debe resaltar que el DNL está confinado a un área específica no mayor a una hoja de papel tamaño carta. El DNL representa 60 % de las condiciones de dolor neuropático. No existe una única etiología. El abordaje diagnóstico es similar al de otros síndromes dolorosos neuropáticos. Se utilizan herramientas diagnósticas generales para evaluar las características clínicas. En la actualidad no existen guías específicas de manejo del DNL, por lo que se utilizan las guías para dolor neuropático en general. En las guías de la Sociedad Canadiense de Dolor se incluyen los tratamientos tópicos como parte de las estrategias de segunda línea. Pese a la falta de guías, los parches de lidocaína a 5 % y los parches de capsaicina a 8 % han demostrado ser efectivos en modelos de DNL.

Abstract Localized neuropathic pain (LNP) is of peripheral origin and is characterized by circumscribed areas of pain with abnormal skin sensitivity or spontaneous symptoms that are characteristic of neuropathic pain, e.g. burning pain. It should be noted that LNP is confined to a specific area no larger than a letter size sheet of paper. LNP accounts for 60 % of neuropathic pain conditions. There is no single etiology of LNP. The diagnostic approach is similar to that for other neuropathic pain syndromes. General diagnostic tools are used to assess clinical features. So far, there are no specific guidelines for the management of LNP; for this reason, guidelines for general neuropathic pain are used. Topical treatments are included as part of second-line strategies in the Canadian Pain Society guidelines. Despite the lack of guidelines, 5 % lidocaine patches and 8 % capsaicin patches have been proven effective in LNP models.

Evaluation of a Protocol For Topical Application of Capsaicine Gel 0.025 % in the Management of Burning Mouth Syndrome Correlating its Impact on Quality of Life

ABSTRACT: The aim of this study is to report the results obtained with a protocol of topical application of capsaicin gel 0.025 % in the management of burning mouth syndrome (BMS) to evaluate the influence of the disease and treatment on their quality of life (QOL) using the OHIP-14 questionnaire (Oral Health Impact Profile). After clinical examination and diagnosis of BMS, 10 patients reported the intensity of the burning by means of a subjective score ranging from 0 to 10 and also answered the OHIP-14. Then, a topical application protocol of capsaicin gel 0.025 % was initiated, with weaning from medication and complete withdrawal within 180 days. At each reassessment consultation (30, 60, 90 and 180 days), the patients answered the OHIP-14 and subjective burning scores were collected again. Overall, the capsaicin gel showed gradual reduction or elimination of symptoms of BMS, as well as an improvement in the QOL of patients throughout treatment. At 180 days, after medication withdrawal, 6 patients (60 %) reported total absence of burning and in four patients (40 %) the score remained or decreased. In one patient (10 %) the score increased, although it remained below the initial score. The results showed an improvement in the QOL of all patients who completed the protocol and the impact of BMS on the QOL decreased in relation to the initial score in all patients. The topical use of 0.025 % capsaicin gel was effective in reducing or remitting symptoms of BMS. The OHIP-14 questionnaire showed the negative impact of BMS on patients' QOL and the role of treatment in its improvement.

RESUMEN: El objetivo de este estudio fue reportar los resultados obtenidos con un protocolo de aplicación tópica de gel de capsaicina al 0,025 % en el manejo del síndrome de boca ardiente (SBA), para evaluar la influencia de la enfermedad y el tratamiento en su calidad de vida (CV) mediante el cuestionario OHIP-14. Tras el examen clínico y diagnóstico de SBA, 10 pacientes refirieron la intensidad del ardor mediante una puntuación subjetiva de 0 a 10 y también respondieron la OHIP-14. Luego, se inició un protocolo de aplicación tópica de gel de capsaicina al 0,025%, con destete de la medicación y retiro completo en 180 días. En cada consulta de reevaluación (30, 60, 90 y 180 días), los pacientes respondieron el OHIP-14 y se recogieron nuevamente las puntuaciones subjetivas de quemado. En general, el gel de capsaicina mostró una reducción o eliminación gradual de los síntomas del SBA, así como una mejora en la calidad de vida de los pacientes durante todo el tratamiento. A los 180 días, después de la retirada de la medicación, 6 pacientes (60 %) informaron ausencia total de ardor y en cuatro pacientes (40%) la puntuación se mantuvo o disminuyó. En un paciente (10 %) la puntuación aumentó, aunque se mantuvo por debajo de la puntuación inicial. Los resultados mostraron una mejora en la CV de todos los pacientes que completaron el protocolo y el impacto de SBA en la CV disminuyó en relación con la puntuación inicial en todos los pacientes. El uso tópico de gel de capsaicina al 0,025 % fue efectivo para reducir o remitir los síntomas del SBA. El cuestionario OHIP-14 mostró el impacto negativo de SBA en la CV de los pacientes y el papel del tratamiento en su mejora.

Capsaicin topical cream (8%) for the treatment of myofascial pain syndrome / Creme tópico de capsaicina (8%) para o tratamento da síndrome da dor miofascial

Abstract Background: Myofascial pain syndrome is a common cause of musculoskeletal pain. The objective of this study was to evaluate the potential analgesic action of 8% capsaicin cream for topical use in patients with myofascial pain syndrome. Methods: Initially, cream formulations of PLA (Placebo) and CPS (Capsaicin 8%) were developed and approved according to the current requirements of the health authority agency. The 40 participating patients were randomly assigned to the PLA and CPS groups in a double-blind fashion. Before the creams were topically administered, according to the allocation group, the local anesthetic was used for a period of 50 minutes directly in the area of interest. The cream was applied to the area of the skin over the trigger point, represented by the area with pain at palpation, in an amount of 10 g for 30 minutes in a circular area of 24 mm diameter. Subsequently, the cream was removed and the skin tolerability parameters were evaluated. The pain was measured before and during the formulation application, as well as at 1 hour, 7 days, 30 days, and 60 days after the procedure, evaluated using a verbal numerical scale (from 0 to 10: with 0 = no pain and 10 = worst pain imaginable). Results: No patient in PLA Group had hyperemia or burning sensation at the site of application, while 85% of patients in CPS Group had hyperemia or burning sensation at 15 minutes. These complaints disappeared 24 hours after the cream was removed. The pain score in CPS Group decreased steadily up to the 60th day of evaluation (p < 0.0001). Conclusion: Application of the formulations did not cause macroscopic acute or chronic skin lesions in patients, and the 8% capsaicin formulation was beneficial and well tolerated.

Resumo Justificativa: A síndrome da dor miofascial é uma causa comum de dor musculoesquelética. O objetivo deste estudo foi avaliar a potencial ação analgésica de 8% do creme de capsaicina para uso tópico em pacientes com síndrome da dor miofascial. Métodos: Inicialmente, as formulações de creme de PLA (Placebo) e CPS (Capsaicina 8%) foram desenvolvidas e aprovadas de acordo com os requisitos atuais da agência de autoridade de saúde. Os 40 pacientes participantes foram distribuídos aleatoriamente e de forma duplo-cega para os grupos PLA e CPS. Antes dos cremes serem administrados topicamente, de acordo com o grupo de alocação, o anestésico local foi usado por um período de 50 minutos diretamente na área de interesse. A administração ocorreu na área da pele sobre o ponto-gatilho, o qual apresentou a área dolorida à palpação, em uma quantidade de 10 g por 30 minutos em área circular com diâmetro de 24 mm. Posteriormente, o creme foi removido e os parâmetros de tolerabilidade à pele foram avaliados. A dor foi medida antes e durante a aplicação da formulação, bem como 1 hora, 7 dias, 30 dias e 60 dias após o procedimento avaliado pela escala numérica verbal (0 a 10, com zero sem dor e dez a pior dor imaginável). Resultados: Nenhum paciente no grupo PLA experimentou hiperemia ou sensação de queimação no local de aplicação do creme, enquanto 85% dos que experimentaram no grupo CPS apresentaram hiperemia ou sensação de queimação 15 minutos. Essas queixas desapareceram 24 horas após a remoção do creme. O escore de dor no grupo CPS diminui de forma sustentada até o 60° dia de avaliação (p < 0,0001). Conclusão: A administração das formulações não causou lesões cutâneas agudas ou crônicas macroscópicas nos pacientes e a formulação de 8% de capsaicina foi benéfica e bem tolerada.

[Capsaicin topical cream (8%) for the treatment of myofascial pain syndrome]. / Creme tópico de capsaicina (8%) para o tratamento da síndrome da dor miofascial.

BACKGROUND: Myofascial pain syndrome is a common cause of musculoskeletal pain. The objective of this study was to evaluate the potential analgesic action of 8% capsaicin cream for topical use in patients with myofascial pain syndrome. METHODS: Initially, cream formulations of PLA (Placebo) and CPS (Capsaicin 8%) were developed and approved according to the current requirements of the health authority agency. The 40 participating patients were randomly assigned to the PLA and CPS groups in a double-blind fashion. Before the creams were topically administered, according to the allocation group, the local anesthetic was used for a period of 50minutes directly in the area of interest. The cream was applied to the area of the skin over the trigger point, represented by the area with pain at palpation, in an amount of 10g for 30minutes in a circular area of 24 mm diameter. Subsequently, the cream was removed and the skin tolerability parameters were evaluated. The pain was measured before and during the formulation application, as well as at 1 hour, 7 days, 30 days, and 60 days after the procedure, evaluated using a verbal numerical scale (from 0 to 10: with 0=no pain and 10=worst pain imaginable). RESULTS: No patient in PLA Group had hyperemia or burning sensation at the site of application, while 85% of patients in CPS Group had hyperemia or burning sensation at 15minutes. These complaints disappeared 24hours after the cream was removed. The pain score in CPS Group decreased steadily up to the 60th day of evaluation (p <0.0001). CONCLUSION: Application of the formulations did not cause macroscopic acute or chronic skin lesions in patients, and the 8% capsaicin formulation was beneficial and well tolerated.

Targeting the hTRPV6 with capsaicinoid inhibitors

Capsaicin is a substance produced by Capsicum peppers with extensive biological activity reported in the literature. Among these studies, it was suggested that the anti-tumor activity is related to modulation of the Transient Potential Receptor Vanilloid (TRPV) channels. Capsaicin is known to bind with very high affinity to TRPV1 (IC50 ≈ 7 nM), triggering the burning sensation followed by analgesia. However, recent studies have suggested that the pro-apoptotic effects of capsaicin are TRPV6-mediated. Herein we report the development of a novel inhibitor of the TRPV6 using two different strategies for compounds design. We generated a series of direct and chimeric capsaicinoids based on the literature compounds, capsaicin, and cis-22a. These analogs were probed against HEK-hTRPV6 and the hits were further optimized. Based on the previous SAR and chemical optimization, we found 56h, named MRC-130, a derivative that remarkably inhibited TRPV6 in the nanomolar range (IC50 = 83 ± 4 nM), possess high selectivity and stability in vitro, and lesser hERG inhibition compared to the reference compound, cis-22a. It is expected that these new molecules would contribute significantly to the study on the TRPV6 function and its role in tumor pathophysiology

Capsaicina é uma substância produzida por pimentas do gênero Capsicum com extensa atividade biológica relatada na literatura. Entre esses estudos, sugeriu-se que a atividade antitumoral esteja relacionada à modulação dos canais TRPV (do inglês, Transient Potential Receptor Vanilloid). Sabe-se que a capsaicina se liga com altíssima afinidade ao TRPV1 (IC50 ≈ 7 nM), desencadeando a sensação de queimação seguida de analgesia. No entanto, estudos recentes sugeriram que os efeitos pró-apoptóticos da capsaicina são mediados pelo TRPV6. Visando o exposto, este trabalho relata o desenvolvimento de um novo inibidor do TRPV6 usando duas estratégias diferentes para o planejamento dos compostos. Geramos séries de capsaicinoides diretos e quiméricos com base nos compostos da literatura, capsaicina e cis-22a. Esses análogos foram analisados contra HEK-hTRPV6 e os análogos mais promissores foram otimizados. Com base na REA e em otimizações químicas anteriores, encontramos 56h, chamado MRC-130, um derivado que inibiu notavelmente o TRPV6 na faixa nanomolar (IC50 = 83 ± 4 nM), possui alta seletividade e estabilidade in vitro e menor inibição de hERG em comparação com o composto de referência, cis-22a. Espera-se que essas novas moléculas contribuam significativamente para o estudo da função do TRPV6 e seu papel na fisiopatologia tumoral

Topical capsaicin for pain in osteoarthritis: A literature review.

Osteoarthritis is the most common joint disorder worldwide. The predominant symptom, pain, is usually treated with acetaminophen or oral non-steroidal anti-inflammatory drugs, although they are associated with a significant risk of side effects. Topical capsaicin may represent an effective and safe alternative. The aim of this review is to examine the evidence for the efficacy and safety profile of topical capsaicin in the management of pain caused by osteoarthritis. Databases were searched for articles published between 2004 and 2016, in Portuguese, English or Spanish, using the search terms "capsaicin" and "osteoarthritis". When compared to placebo, it was found that topical capsaicin has a good safety profile and efficacy in reducing osteoarthritis pain of the hand, knee, hip or shoulder. However, the studies have significant limitations, the most important the difficulty of blinding. It is attributed to this review the strength of recommendation B.

Inibição do sistema quorum sensing AI-1 por Capsicum frutescens e Capsicum annuum em bactérias Gram-negativas / Inhibition of AI-1 quorum-sensing system by Capsicum frutescens and Capsicum annuum in Gram-negative bacteria

A inibição do quorum sensing (QS) altera a comunicação bacteriana, reduzindo a expressão de fatores de virulência e a formação de biofilmes, o que pode conferir menor pressão seletiva em comparação aos antibióticos tradicionais. As frutas e hortaliças constituem uma fonte rica em compostos com propriedades potenciais de inibição do QS. Entretanto, há pouca referência sobre o potencial de pimentas do gênero Capsicum e de seus compostos isolados como inibidores do QS. Esse trabalho teve como objetivo avaliar o efeito de extratos orgânicos obtidos das variedades de pimenta-malagueta e pimentão vermelho sobre o sistema QS dependente do sinalizador AI-1 (acil homoserina lactona - AHL) em bactérias Gram-negativas. Os extratos foram obtidos por extração em fase sólida e separados em uma fração metanólica e outra amônica; sendo os compostos característicos identificados e quantificados por cromatografia líquida de alta eficiência (CLAE). A atividade antimicrobiana dos extratos foi avaliada pela determinação da concentração inibitória mínima (MIC) e pela curva de crescimento de Chromobacterium violaceum ATCC 12472, Serratia liquefaciens MG1 e Pseudomonas aeruginosa PAO1. O efeito anti-QS dos extratos foi avaliado pelos testes de difusão em ágar e quantificação da produção de violaceína em meio líquido por C. violaceum e sobre a formação de biofilme, avaliado pelo ensaio de cristal violeta e microscopia confocal, em S. liquefaciens e P. aeruginosa nas temperaturas 30 ºC e 37 ºC. Os resultados obtidos pela CLAE indicaram que o extrato metanólico de pimenta-malagueta (EMPM) continha capsaicinoides como a capsaicina e dihidrocapsaicina, luteolina e outros compostos não identificados; já o extrato amônico desta não continha os compostos capsaicinoides. Ambos os extratos de pimentão vermelho continham luteolina e compostos não identificados, mas não apresentaram capsaicinoides. Como o EMPM era representativo dos demais extratos, por conter tanto capsaicinóides quanto luteolina, o foco deste trabalho foi avaliar os efeitos do EMPM sobre fenótipos microbianos nas concentrações 5; 2,5; 1,25 e 0,625 mg/ml, além de utilizar a capsaicina como controle comparativo em concentrações equivalentes às do extrato (25, 50 e 100 µg/ml). Os resultados da atividade antimicrobiana mostraram inibição parcial do crescimento das bactérias nas concentrações sub-MIC (MIC >5 mg/ml) de 5 e 2,5 mg/ml de EMPM. A capsaicina também inibiu parcialmente o crescimento das bactérias a 100 µg/ml, com exceção de S. liquefaciens a 37 ºC, cujo crescimento foi induzido em 50 e 25 µg/ml. A produção de violaceína foi reduzida pelo EMPM a 1,25 e 0,625 mg/ml, sem afetar o crescimento de C. violaceum. Ensaios com C. violaceum CV026, estirpe biosensora capaz de produzir o pigmento na presença de AI-1 exógeno, sugerem que o possível mecanismo de atuação do extrato sobre o sistema QS em C. violaceum 12472 é sobre a síntese do sinalizador, já que não foi observada inibição da produção de violaceína em CV026 pelo extrato. Contrariamente, a capsaicina incrementou a produção do pigmento na estirpe 12472, mas ensaios com a estirpe CV026 indicaram que a capsaicina não atua como sinalizador do QS, uma vez que esta não induziu a produção de violaceína nesta estirpe. Já a formação de biofilme foi incrementada na presença do EMPM, sendo consideravelmente maior em P. aeruginosa a 30 ºC. Igualmente, observou-se indução da formação de biofilme por capsaicina em S. liquefaciens (37 ºC) e P. aeruginosa (30 ºC). Porém, a capsaicina não teve efeito sobre a formação de biofilme de S. liquefaciens quando cultivada a 30 ºC, nem P. aeruginosa a 37 ºC. Os resultados revelam que a produção de violaceína em C. violaceum ATCC 12472 é inibida pelo EMPM, mas não pela capsaicina. Já, o EMPM e a capsaicina, de forma geral, não inibem a formação de biofilme de S. liquefaciens MG1 nem P. aeruginosa PAO1. Outros estudos são necessários para elucidar os mecanismos pelos quais o EMPM e a capsaicina agem sobre os fenótipos avaliados neste trabalho

Quorum sensing inhibition alters bacterial communication by reducing virulence factors expression and biofilm formation, exerting less selective pressure compared to antibiotics. Fruits and vegetables are rich sources of compounds with potential QS-inhibition properties. However, there are few references about the potential of peppers belonging to the genus Capsicum and its isolated compounds as QS inhibitors. This study aimed to assess the effect of organic extracts obtained from Capsicum varieties, pimenta-malagueta (red chili) and pimentão vermelho (red bell pepper), on the AI-1 dependent QS system. The extracts were obtained by solid phase extraction and split into a methanolic and an ammonic fraction. Characteristic compounds were identified and quantified by high performance liquid chromatography (HPLC). The antimicrobial activity of the extracts was assessed by determining the minimal inhibitory concentration (MIC) and the growth curve of Chromobacterium violaceum ATCC 12472, Serratia liquefaciens MG1 and Pseudomonas aeruginosa PAO1. The anti-QS effect of the extracts was evaluated by the agar diffusion assay and the quantification of violacein production was assessed in liquid medium by C. violaceum, as well as in the biofilm formation test determined by the crystal violet assay and confocal microscopy with S. liquefaciens and P. aeruginosa at 30 ºC and 37 ºC. HPLC results showed that the methanolic extract of pimenta-malagueta (EMPM) contained capsaicinoids such as capsaicin and dihidrocapsaicin, luteolin and other unidentified compounds in lower concentrations; while its ammonic extract did not have capsaicinoids. Both pimentão vermelho extracts contained luteolin and other unidentified compounds in low concentrations, but they did not contain capsaicinoids. As EMPM was representative among the extracts because it contained capsaicinoids and luteolin, the focus of this work was to assess the effect of EMPM over microbial phenotypes at concentrations of 5, 2.5, 1.25 and 0.625 mg/ml, using capsaicin as a comparative control at equivalent concentrations to those in EMPM (25, 50 and 100 µg/ml). Antimicrobial activity assays showed a partial inhibition growth of bacteria at sub-MIC concentrations (MIC >5 mg/ml) of EMPM at 5 and 2.5 mg/ml. Similarly, capsaicin partially inhibited bacterial growth at 100 µg/ml, except for S. liquefaciens at 37 ºC in which growth was induced at 50 and 25 µg/ml. Violacein production was reduced by EMPM at 1,25 and 0,625 mg/ml without affecting C. violaceum growth. Assays with C. violaceum CV026, a biosensor strain that produces violacein in the presence of exogenous AI-1, suggest that EMPM reduced violacein production in C. violaceum 12472 by interfering with the AI-1 synthesis. In contrast, capsaicin incremented violacein synthesis in strain 12472, but experiments with strain CV026 revealed that capsaicin does not function as an analog of AI-1. Biofilm formation was increased in EMPM presence, being remarkably superior in P. aeruginosa cultivated at 30 ºC, as opposed to cultivation at 37 ºC. Similarly, capsaicin induced biofilm formation in S. liquefaciens (37 ºC) and P. aeruginosa (30 ºC). However, capsaicin did not affect biofilm formation on S. liquefaciens cultured at 30 ºC, neither on P. aeruginosa at 37 ºC. These results show that violacein production in C. violaceum ATCC 12472 is inhibited by EMPM, but not by capsaicin. In general, EMPM and capsaicin did not inhibit biofilm formation in S. liquefaciens MG1 neither in P. aeruginosa PAO1. More studies are necessary to elucidate the mechanisms by which EMPM and capsaicin affect the studied phenotypes in this work

EFECTO DE LA LIOFILIZACIÓN SOBRE LAS PROPIEDADES FUNCIONALES DEL AJÍ ROCOTO (Capsicum pubescens)

El ají rocoto (Capsicum pubescens) es un fruto perecedero, por lo cual, se hace necesario explorar alternativas agroindustriales, que permitan conservar sus propiedades funcionales. Entre los desarrollos tecnológicos estudiados en la transformación y la conservación de alimentos, se encuentra la liofilización. En esta investigación, se liofilizó ají rocoto, colectado en San Cristóbal-Medellín, Antioquia (Colombia) y se evaluó su efecto sobre las propiedades funcionales, como la capacidad antioxidante, por el método Ferric Reducing Antioxidant Power (FRAP), fenoles totales, carotenoides, contenido de ácido ascórbico y capsaicina, tanto en el producto fresco como en los tratamientos liofilizados. Se realizó un arreglo de parcelas dividas, con el factor de la programación de la velocidad de calentamiento, entre 0,02 y 0,05°C/ min, durante la sublimación, asignado a la parcela principal y al factor categórico de semilla en la subparcela, con una aleatorización completamente al azar (DCA), con tres repeticiones. Se registró, que el ají rocoto fresco con semilla incluida, la placenta valores de 1,18mg, equivalentes de ácido ascórbico/g base seca (b.s.), como capacidad antioxidante, por FRAP; 5,37mg, equivalentes de ácido gálico/g b.s., para el contenido de fenoles totales; 4,74mg/g, b.s. de carotenoides; 1,88mg/g b.s., de ácido ascórbico y 1,57mg/g b.s., de capsaicina. Se concluyó que para los tratamientos liofilizados con y sin semillas, se incrementó la capacidad antioxidante y fenoles totales con respecto al producto en fresco. Se evidenció diferencia estadística en las programaciones de calentamiento durante la sublimación, afectando el contenido de capsaicina, en los tratamientos con y sin semillas.

The chili pepper (Capsicum pubescens) is a perishable fruit whereby it is necessary to explore agroindustrial alternatives, that preserves its functional properties; within the technological developments studied in food processing and preservation is freeze-drying. In this research, the rocoto chili pepper harvested in rural area of San Cristobal-Medellin, Antioquia (Colombia), was freeze-drying and it was evaluated the effect on the functional properties such as antioxidant capacity by the Ferric Reducing Antioxidant Power method (FRAP), total phenols, carotenoids, ascorbic acid and capsaicin, both in the fresh product and in freeze- drying treatments. Was realized a fix split plots, with the factor of programming the heating rate, between 0.02 and 0.05°C/min during sublimation assigned to the principal plot and the categorical factor seeds in the subplot, was performed with a Randomized Block Design (RBD) with three replications. It was obtained in fresh chilli with seed including placenta values of 1.18mg of eq. ascorbic acid/g dried basis (d.b.) as antioxidant capacity by FRAP; 5.37mg of eq. gallic acid/g d.b. for total phenols content; 4.74mg/g d.b. of carotenoids; 1.88mg/g d.b. of ascorbic acid and 1.57mg/g d.b. of capsaicin. It was concluded that for the freeze-drying treatments, the antioxidant capacity and total phenols were increased, with respect to the fresh product. It evidenced a statistical difference in the heating schedules during sublimation affecting the capsaicin content in seed and seedless treatments.

Expression and distribution of kinin B2 receptor in medulla and spinal cord tissues of Rats treated with capsaicin / Expresión y distribución del receptor B2 de cininas en la médula y tejido medular espinal de ratones tratados con capsaicina

Kinins are vasoactive peptides that promote pain and inflammation, yet centrally believed to participate to cardiovascular defensive reflexes produced by noxious stimuli. These peptides signal through the activation of two transmembrane G-protein-coupled receptors named B1 and B2 receptors (B1R and B2R). The B2R is constitutive in healthy tissues and animals. The aim of the study was to measure the gene and protein expression of B2R kinin receptors in central and peripheral tissues isolated from control rats and rats were pre-treated with capsaicin on the second day of life (50 mg/kg, s.c.) or two weeks prior to sacrifice (125 mg/kg over three days, s.c.). The same treatment with saline was made in control animals. Levels of mRNA for B2R were measured by quantitative RT-PCR and Qualitative while receptor binding sites were measured on tissue sections with the radioligands 125I-HPP-Hoe 140 (B2R). B2R was expressed in all studied tissues (hypothalamus, paratrigeminal nucleus, nucleus of solitary tract, spinal cord, aorta and liver) and treatment capsaicin neonates when compared to controls, did not affect its level of expression. Capsaicin had no significant effect on the expression of B2R in some tissues on binding sites. The synthesis of B2R kinin receptor is not associated with sensory C-fibre and tissues showed no significant difference indicating that B2R was regulated by distinct mechanisms.

Las cininas son péptidos vaso activos que participan de mecanismos de dolor e inflamación, con la promoción de reflejos cardiovasculares defensivos producidos por estímulos nocivos. Estos péptidos señalizan por medio de la activación de dos receptores transmembrana acoplados a proteína G llamados receptores B1 y B2 (B1R y B2R). El B2R es constitutivo en tejidos saludables y en animales. El objetivo de este estudio consistió en tomar las medidas de la expresión del gen y la proteína del receptor B2R de cinina en tejidos centrales y periféricos aislados de ratones control y ratones pre tratados con capsaicina en el segundo día de vida (50 mg/kg, s.c.) o con dos semanas antes del sacrificio (125 mg/kg por tres días, s.c.). El mismo tratamiento fue hecho con solución salina en los animales control. Fueron medidos niveles de mRNA para B2R por RT-PCR en forma cuantitativa y cualitativa, en cuanto los sitios de unión del receptor fueron medidos en secciones de tejido con radioligante 125I-HPP-Hoe 140 (B2R). B2R fue expresado en todos los tejidos estudiados (hipotálamo, núcleo paratrigeminal, núcleo del tracto solitario, médula espinal, aorta e hígado). El tratamiento con capsaicina en ratones neonatos comparados con controles no presentaron afectación del nivel de expresión. Por otro lado, la capsaicina no tuvo efecto significante en la expresión de los sitios de unión de B2R en los tejidos. La síntesis del receptor B2R de cininas no está asociado con fibras C sensoriales así como los tejidos no mostraron diferencias significativas indicando que B2R es regulado por mecanismos distintos.

Papel da capsaicina de uso tópico em modelo murino de alergia alimentar / Topical use of capsaicin in murine model of food allergy

A alergia alimentar é uma reação de hipersensibilidade imediata mediada por lgE que ocorre com a ingestão de alimentos alergênicos após sensibilização prévia. t: considerada um importante problema de saúde pública mundial, afetando cerca de 7% de crianças e 2% de adultos, com crescente prevalência em países desenvolvidos e em desenvolvimento. Hipoteticamente, agentes anti-inflamatórios poderiam contribuir para o controle de algumas manifestações da alergia. Um candidato a tal efeito e a capsaicina (8-metil-N-6-vanilil-nonenamida), principal componente picante da pimenta, que possui ação analgésica e anti-inflamatória quando aplicada topicamente. Este estudo avaliou o efeito do uso t6pico de capsaicina nas manifestações da alergia alimentar. Para tanto, camundongos BALB/c foram sensibilizados com ovalbumina (OVA) com posterior desafio oral com solução de clara de ovo a 20%. A partir do desafio oral até a eutanásia, animais do grupo capsaicina (ALE-CAP) foram tratados com creme capsaicina a 0,075%, enquanto que animais alérgicos (ALE) foram tratados apenas com o creme base. Os resultados mostram o aumento da concentração sérica de lgE e lgG1 anti-OVA em ambos os grupos, como esperado pelo protocolo de sensibilização. Porém, em relação ao grupo alérgico(ALE), animais do grupo ALE CAP apresentaram um perfil mais favorável, como visto pela maior ingestão do alérgeno, menor perda de peso, redução da infiltração de eosinófilos e neutrófilos (avaliados indiretamente pela atividade de enzimas EPO eMPO, respectivamente) e menor produção de muco pelas células caliciformes. Os resultados sugerem que o tratamento t6pico com capsaicina leva a uma melhora de algumas das manifestações mais importantes da alergia como a inflamação intestinal e a perda de peso. Esse fato pode estar relacionado a inibição do canal TRPV1, atuando indiretamente em vias de sinalização de células TC04•, mast6citos e basófilos, aumentando o limiar de ativação de tais células e, assim...

Food allergy is an immediate hypersensitivity reaction mediated by lgE whichoccurs with the ingestion of allergenic foods after previous sensitization. It is considered a major problem of public health worldwide, affecting about 7% of childrenand 2% of adults, with increasing prevalence in developed and developing countries. Hypothetically, anti-inflammatory agents could contribute to the control some allergy symptoms. A candidate for this purpose is the capsaicin (8-methyl-N-vanillyl-6-nonenamide), the main pungent component of red pepper, having analgesic and anti- inflammatory actions when applied topically. This study evaluated the effect of topical treatment of capsaicin in some food allergy maniestations. For this purpose BALB/c mice were sensitized with ovalbumin (OVA) with subsequent oral challenge with 20% egg yolk solution. From the oral challenge to euthanasia, animals of capsaicin group(CAP) were topically treated with a capsaicin cream (0.075% in cream base) while the allergic group (ALE) were treated with the cream base (without capsaicin). The results showed that there was an increase in serum lgE and anti-OVA lgG1 in both groups, as expected with this from sensitization protocol. However, compared to allergic group(ALE), animals from CAP group presented a more favorable profile, as suggested by the higher intake of allergen, reduced weight loss, reduced eosinophil and neutrophilinfiltrations (assessed indirectly by the activity of the enzymes EPO and MPO, respectively) and lower production of mucus by goblet cells. The results suggest that topical treatment with capsaicin leads to an improvement of some of the most important manifestations allergy such as intestinal inflammation and weight loss. These effects may be related to inhibition of TRPV1 channel, acting indirectly on CD4+ T cell, mastcells and basophils signaling, increasing their activation thre shold and thus decreasing the inflammatory process...

Canales iónicos Receptores de Potencial Transitorio y su papel protagónico en la terapia analgésica / Transient receptor potential ion channels and their leading role in analgesic therapy

En la búsqueda de nuevas opciones terapéuticas para el tratamiento del dolor, se ha llegado al descubrimiento de canales iónicos que actúan como receptores y están presentes en neuronas nociceptoras aferentes primarias. Entre estos receptores, se encuentran los canales iónicos receptores de potencial transitorio que regulan las vías involucradas en el dolor y la nocicepción. Se realizó una revisión actualizada de los principales canales iónicos receptores de potencial transitorio implicados en la fisiopatología del dolor. Se hace una reseña histórica del descubrimiento de estas moléculas y sus estudios avanzados. A continuación se revisan las diferentes familias de estos canales con su clasificación, nomenclatura, estructura y funciones celulares. También se hace un recuento de la relación de estos canales con la analgesia, así como el mecanismo de acción de algunos analgésicos que actúan sobre ellos. Finalmente, se detallan importantes consideraciones a tomar en cuenta, que pudieran influir sobre la utilización de estos medicamentos en la clínica. Por tal motivo, el trabajo procura ser una revisión que abarque el rol de los canales TRP como nuevas dianas farmacológicas en el tratamiento del dolor.

In the search for new therapeutic options for pain treatment, new ion channels have been discovered, which act as receptors and are present in primary afferent nociceptor neurons. Some of them are the transient receptor potential ion channels that regulate the pathways involved in pain and nociception. An updated review of the main transient potential receptors ion channels involved in pain physiopathology and a historical review of the discovery of these molecules and advanced studies on them were also made. Then the different families of these channels with their classification, nomenclature, structure and cell functions were also examined. An account of the relationships of these channels with analgesia as well as the mechanism of action of some analgesics acting upon them was also presented. Finally, important considerations were given, which should be taken into account since they might influence on the clinical use of these drugs. For these reasons, the paper intends to be a review covering the role of the transient receptor potential channels as new pharmacological targets in the pain treatment.

Liposomal topical capsaicin in post-herpetic neuralgia: a safety pilot study / Capsaicina lipossomal tópica na neuralgia pós-herpética: um estudo piloto de segurança

Topical treatments have gained popularity for general use as an adjunct to systemic drugs in neuropathic pain, but their use produces variable clinical results and local adverse events. Objective To evaluate the safety and analgesic effect of a formulation of liposomal capsaicin (LC) (0.025%) in patients with post herpetic neuralgia (PHN). Method Patients who remained symptomatic after first-and second-line treatment were randomized to receive LC for six weeks in a placebo-controlled, crossover design study. Clinical assessment was performed at baseline, in the second, fourth and sixth week of treatment. Results Thirteen patients completed both treatment periods. Visual Analog Scale (VAS) was significantly decreased after the end of the study (p = 0.008), however the effect of treatment was not significant (p = 0.076). There was no difference on global impression of change and other pain characteristics. LC was safe and well tolerated. However, at the concentration used, its analgesic effects were marginal and not significant. .

Os tratamentos tópicos ganharam popularidade para uso geral como um adjuvante de medicamentos sistêmicos na dor neuropática, mas seu uso produz resultados clínicos variáveis e eventos adversos locais. Objetivo Avaliar o efeito de segurança e analgesia de uma formulação de capsaicina lipossomal (LC) (0,025%) em pacientes com neuralgia pós-herpética. Método Os pacientes que permaneceram sintomáticos após tratamento de primeira e de segunda linha foram randomizados para receber LC durante seis semanas em um estudo cruzado controlado por placebo. A avaliação clínica foi realizada no início do estudo, na segunda, quarta e sexta semana de tratamento. Resultados Treze pacientes completaram dois períodos de tratamento. Escala Visual Analógica diminuiu significativamente após o final do estudo (p = 0,008), no entanto, o efeito do tratamento não era significativo (p = 0,076). Não houve diferença na impressão global de mudança e de outras características da dor. LC foi segura e bem tolerada. No entanto, para a concentração utilizada, os seus efeitos analgésicos foram marginais e não significativos. .

Canales iónicos Receptores de Potencial Transitorio y su papel protagónico en la terapia analgésica / Transient receptor potential ion channels and their leading role in analgesic therapy

En la búsqueda de nuevas opciones terapéuticas para el tratamiento del dolor, se ha llegado al descubrimiento de canales iónicos que actúan como receptores y estßn presentes en neuronas nociceptoras aferentes primarias. Entre estos receptores, se encuentran los canales iónicos receptores de potencial transitorio que regulan las vías involucradas en el dolor y la nocicepción. Se realizó una revisión actualizada de los principales canales iónicos receptores de potencial transitorio implicados en la fisiopatología del dolor. Se hace una reseña histórica del descubrimiento de estas moléculas y sus estudios avanzados. A continuación se revisan las diferentes familias de estos canales con su clasificación, nomenclatura, estructura y funciones celulares. También se hace un recuento de la relación de estos canales con la analgesia, así como el mecanismo de acción de algunos analgésicos que actúan sobre ellos. Finalmente, se detallan importantes consideraciones a tomar en cuenta, que pudieran influir sobre la utilización de estos medicamentos en la clínica. Por tal motivo, el trabajo procura ser una revisión que abarque el rol de los canales TRP como nuevas dianas farmacológicas en el tratamiento del dolor(AU)

In the search for new therapeutic options for pain treatment, new ion channels have been discovered, which act as receptors and are present in primary afferent nociceptor neurons. Some of them are the transient receptor potential ion channels that regulate the pathways involved in pain and nociception. An updated review of the main transient potential receptors ion channels involved in pain physiopathology and a historical review of the discovery of these molecules and advanced studies on them were also made. Then the different families of these channels with their classification, nomenclature, structure and cell functions were also examined. An account of the relationships of these channels with analgesia as well as the mechanism of action of some analgesics acting upon them was also presented. Finally, important considerations were given, which should be taken into account since they might influence on the clinical use of these drugs. For these reasons, the paper intends to be a review covering the role of the transient receptor potential channels as new pharmacological targets in the pain treatment(AU)

Periapical tissue repair of dog teeth after intracanal administration of capsaicin 0.075% / Reparação tecidual periapical em dentes de cão após administração intracanal de capsaicina 0.075%

O objetivo deste estudo foi realizar uma avaliação descritiva sobre a reparação tecidual da região periapical de dentes de cães. Material e Métodos: Foram utilizados trinta e seis canais radiculares, sendo dezoito preenchidos com capsaicina 0,075% e hidróxido de cálcio (pasta teste) e os outros dezoito canais preenchidos com hidróxido de cálcio (grupo controle). As análises histológicas foram realizadas para classificar a inflamação como ausente, leve, moderada ou grave. As análises também classificaram a presença ou ausência da reparação tecidual nos períodos de 7, 14 e 30 dias. Resultados: O uso de capsaicina 0,075% não alterou a resposta inflamatória e reparação quando comparado ao grupo controle. Conclusão: Nossos dados sugerem que o grupo teste, o qual utilizou capsaicina 0,075% como pasta intracanal, pode ser indicado para reparação tecidual. Além disso, outros experimentos devem ser realizados para avaliar a possível utilização clínica da capsaicina para odontalgias atípicas...

Objective: The aim of this study was make a descriptively evaluate the repair of the periapical region of dog teeth. Material and Methods: Thirty-six root canals were used, eighteen were filled with 0.075% capsaicin and calcium hydroxide (test paste) and the rest eighteen root canals were filled with calcium hydroxide (control group). Histological analyzes were performed to classify inflammation as absent, mild, moderate or severe. The analyses also classified the presence or absence of repair at 7, 14 and 30 days. Results: The use of 0.075% capsaicin did not modify the inflammatory response and repair when compared to control group. Conclusion: Our data suggests that test group with 0.075% capsaicin as intracanal administration could be indicated for tissue repair; furthermore other experiments should be carried out to evaluate possible clinical use of capsaicin for atypical odontalgia...