Diss.--Philosophisch-Historische Fakultät--Basel, 1997. / Bibliogr. p. 299-321. Notes bibliogr.

Diss.--Mediz.--Zürich--Medizinhistorischer Institut. / Bibliogr. p. 267-278. Index.

Thèse--Paris. / Includes bibliographical references.

Thesis (Honors)--College of William and Mary, 2008. / Includes bibliographical references (leaves 43-45). Also available via the World Wide Web.

Research into the mechanisms of hyperalgesia is ongoing with the goal of improving clinical management of chronic pain. One animal model of chronic musculoskeletal pain uses two injections of acidic saline into a lateral gastrocnemius muscle to induce a long-lasting bilateral decrease in paw withdrawal thresholds. This study tested whether the two injections need to occur in the same muscle. Male Sprague-Dawley rats were injected with acidic saline (pH 4.0) in either the lateral or medial head of gastrocnemius or the contralateral gastrocnemius (lateral head). All animals received a second injection in the ipsilateral gastrocnemius (lateral head). Mechanical withdrawal thresholds were reduced in all groups when tested 24 hours after the second injection. Animals in which the first muscle injection was substituted with a non-specific treatment (intraperitoneal injection of lipopolysaccharide) developed bilateral hyperalgesia after a single acidic saline injection. Thus, the mechanism of hyperalgesia in this model is not restricted to the injected tissues and may include central nervous system structures. Consistent with this, an inhibitor of glia cell activation (minocycline) blocked the development of bilateral hyperalgesia. These data indicate that the central nervous system may play a large role in mediating chronic musculoskeletal pain. / October 2007

El síndrome aurículo-temporal, también conocido como síndrome de Frey, es una entidad clínica caracterizada por presentar sudoración en la región preauricular coincidiendo con las comidas.Este cuadro aparece en algunos pacientes que han sido sometidos a parotidectomías, generalmente por tumoraciones benignas, debido a una reinervación aberrante de las fibras parasimpáticas colinérgicas que inervaban las glándulas parótidas, un periodo variable de alrededor de 6 meses es lo que tardan las terminales nerviosas en alcanzar la piel, sinaptando a nivel de la dermis liberando la acetilcolina a este nivel. Esto produce en el momento de la ingesta enrojecimiento (por vasodilatación cutánea) y sudoración (por activación de las glándulas sudoríparas ecrinas) en la región preauricular.En el presente estudio, se ha seleccionado una población de pacientes afectos de síndrome de Frey y se les ha propuesto entrar en estudio para determinar la utilidad de la toxina botulínica A para su tratamiento.Los pacientes que aceptaron entrar en el estudio, fueron sometidos a un cuestionario y se les realizó el test de Minor, para cuantificar y delimitar la afectación inicial.En los pacientes en los que se objetivó un síndrome de Frey significativo, se llevó a cabo la inyección intradérmica de toxina botulínica A. La dosis utilizada fue de 10 unidades/cm².Los pacientes fueron sometidos a un estrecho seguimiento durante las semanas siguientes a la inyección. No se observaron efectos secundarios ni reacciones adversas en ningún paciente. En torno al quinto día post-inyección los pacientes presentaron una desaparición total de la sudoración coincidente con las comidas en la zona afecta. Los pacientes se mantuvieron asintomáticos un periodo variable de tiempo, cuya media ha sido de diez y seis meses.En comparación con las diversas alternativas quirúrgicas (interposición de colgajos o de materiales aloplásticos) y no quirúrgicas (medicamentos varios, Iontoforesis o radioterapia) disponibles en la actualidad para el tratamiento del cuadro, el tratamiento con toxina botulínica A se ha mostrado como un tratamiento que sitúa a esta modalidad terapéutica al frente del arsenal terapéutico disponible.Conclusiones1. La inyección intradérmica de toxina botulínica A es un método efectivo para controlar los síntomas de sudoración y enrojecimiento presentes en el síndrome aurícula-temporal establecido.2. La inyección a altas dosis de toxina botulínica A en la región afectada no ha desencadenado, ni a nivel local, ni a nivel sistémico, efectos secundarios.3. Se trata de un procedimiento de fácil aplicación en la consulta médica sin necesidad de ingreso, ni de hacer uso de las instalaciones quirúrgicas, ya que posee un carácter claramente ambulatorio.4. La técnica presenta una baja morbilidad, ya que en ningún casos se produjeron efectos adversos durante, ni como consecuencia de la inyección.5. Se trata de una técnica reproducible y protocolizable, y además una vez finalizado el efecto puede repetirse.6. La duración del efecto libre de sudoración aplicando una dosis de 10 U/ cm² fue de 16 meses de media. / The auricular-temporal syndrome also known as Frey´s síndrome or gustatory sweatting is carachterized for presentting sweatting in the preauricular region during meals. This pathology appears in some patients that have been operated of a parotid tumour, generally because of benign tumours, due to the aberrant reinervation of parasympathetic cholinergic fibbers that normally innervated the parotid gland.An average time of six months after the surgery, which is the time needed for the nerves to reach the skin and establish a new synapses in the dermis, allowing acetylcholine into the synapses at this level.During meals patients experience flushing (due to vasodilatation) and sweating (because of the activation of the sweat glands located on the dermal part of the skin) on the preauricular region.In this study, we reviewed the patients that had been operated of a parotid tumour, and we selected the patients who presented the auricular-temporal syndrome, they were asked to join the study with botullinum toxin A.The patients that accepted to join the study, were asked to answer a questionnaire and we carried a Minor's test in all of them in order to quantify the surface of skin affected.In the patients that we observed a clinical significant Frey's syndrome we proceeded to the intradermal injection of botullinum toxin A. The dose used was of 10 IU/cm².The patients were followed during the weeks after the injection. Neither secondary effects nor adverse reactions were observed.The fifth day after day after the injection the sweating and flushing disappeared in all the patients when the Minor's test was carried out. Patients stayed free of symptoms for an average time of sixteen months.Comparing our results with the surgical and nonsurgical procedures that can be nowadays performed in order to solve the Frey´s syndrome, the treatment with botullinum toxin A has shown a better result and no complications.Conclusions1. The intradermal injection of botullinum toxin A is an effective method to control the symptoms of sweating and flushing on the preauricular region on those patients affected of auricular-temporal syndrome.2. The injection with high doses of botullinum toxin A in the affected region has not developed any adverse effect, either locally or systemically.3. It's a procedure that can be easily carried on the consultations, without need of sleeping in the hospital, and also without having to make use of the operation room.4. This technique showed a very low morbidity, none of the cases developed any secondary effects during or after the injection.5. The technique can be reproduced easily and standardized, and once finished the effect the technique can be repeated again.6. The time free of symptoms with the dose of 10 IU/ cm² was of an average of 16 months.

Dissertation--Medizinische Fakultät--Universität Leipzig. / Bibliogr. p. 86-96.

Research into the mechanisms of hyperalgesia is ongoing with the goal of improving clinical management of chronic pain. One animal model of chronic musculoskeletal pain uses two injections of acidic saline into a lateral gastrocnemius muscle to induce a long-lasting bilateral decrease in paw withdrawal thresholds. This study tested whether the two injections need to occur in the same muscle. Male Sprague-Dawley rats were injected with acidic saline (pH 4.0) in either the lateral or medial head of gastrocnemius or the contralateral gastrocnemius (lateral head). All animals received a second injection in the ipsilateral gastrocnemius (lateral head). Mechanical withdrawal thresholds were reduced in all groups when tested 24 hours after the second injection. Animals in which the first muscle injection was substituted with a non-specific treatment (intraperitoneal injection of lipopolysaccharide) developed bilateral hyperalgesia after a single acidic saline injection. Thus, the mechanism of hyperalgesia in this model is not restricted to the injected tissues and may include central nervous system structures. Consistent with this, an inhibitor of glia cell activation (minocycline) blocked the development of bilateral hyperalgesia. These data indicate that the central nervous system may play a large role in mediating chronic musculoskeletal pain.

Research into the mechanisms of hyperalgesia is ongoing with the goal of improving clinical management of chronic pain. One animal model of chronic musculoskeletal pain uses two injections of acidic saline into a lateral gastrocnemius muscle to induce a long-lasting bilateral decrease in paw withdrawal thresholds. This study tested whether the two injections need to occur in the same muscle. Male Sprague-Dawley rats were injected with acidic saline (pH 4.0) in either the lateral or medial head of gastrocnemius or the contralateral gastrocnemius (lateral head). All animals received a second injection in the ipsilateral gastrocnemius (lateral head). Mechanical withdrawal thresholds were reduced in all groups when tested 24 hours after the second injection. Animals in which the first muscle injection was substituted with a non-specific treatment (intraperitoneal injection of lipopolysaccharide) developed bilateral hyperalgesia after a single acidic saline injection. Thus, the mechanism of hyperalgesia in this model is not restricted to the injected tissues and may include central nervous system structures. Consistent with this, an inhibitor of glia cell activation (minocycline) blocked the development of bilateral hyperalgesia. These data indicate that the central nervous system may play a large role in mediating chronic musculoskeletal pain.

Submitted by Sandra Pereira (srpereira@ufrrj.br) on 2016-08-24T15:39:27Z No. of bitstreams: 1 2011 - Raphael Andrade de Castro.pdf: 917522 bytes, checksum: f65a225b9fc808c90016c649f5cb2be1 (MD5) / Made available in DSpace on 2016-08-24T15:39:27Z (GMT). No. of bitstreams: 1 2011 - Raphael Andrade de Castro.pdf: 917522 bytes, checksum: f65a225b9fc808c90016c649f5cb2be1 (MD5) Previous issue date: 2011-02-18 / causing pain as a constant feature. The pyrazole compounds are the drugs of synthetic origin in their chemical structure consisting of a ring pirazol?nico, with which several studies show the effectiveness in controlling of pain, fever and inflammation. The need to develop new drugs with analgesic and anti-inflammatory, low cost and which have few adverse reactions, has stimulated the synthesis and study of pharmacological activities of pyrazole compounds. With this objective, we studied the antinociceptive and anti-inflammatory potential of compound 1.5-diphenyl-pyrazole-3-hidrazinopirazol(a) (DHP), administered orally in pharmacological models of the acetic acid writhing, tail-flick, formalin, ear edema induced by croton oil and carrageenan-induced peritonitis in mice, and mechanical allodynia (von Frey) and thermal hyperalgesia (Hargreaves) in rats. The administration of DHP (1, 3 and 10mg/kg) decreased in a dose-dependent (41.3, 62.7 and 76%) number of writhing (ID50 = 1.3mg/kg). In the tail-flick test, DHP (10mg/kg) was ineffective and the application of positive control fentanyl (200?g/kg, sc) increased the latency to thermal stimulation in up to 138%. Without changing the first phase of nociception (neurogenic pain) of the formalin test, DHP (10mg/kg) and the positive control indomethacin (10mg/kg, p.o.) inhibited the reactivity in the 2 phase (ndinflammatory pain) in 40.9 and 48.7% respectively. This same dose of DHP reduced by 54% the ear edema induced by croton oil, as well as the positive control, dexamethasone (2mg/kg, sc) at 55.3%. Also in a dose-dependent DHP (3, 10 and 30 mg / kg) inhibited by 11.8, 39 and 53.7%, respectively, leukocyte migration in peritonitis induced by carrageenan test (ID50 = 22.9mg/kg). In the assessment of mechanical allodynia incision group treated with DHP (GIDHP - 10mg/kg) showed a significant reversal of allodynia (RA) after one hour of administration, with maximum reading RA for 12 hours (28.2%) in the second stage of the experiment, remaining in the third stage with RA of 26.9, 43.4 and 60.4% in the 7th, 10th and 14th days of evaluations, when compared with the vehicle group incised (GIV). In thermal hyperalgesia GIDHP (10mg/kg) also significantly reversed the hyperalgesia (RH) after one hour of treatment, with RH maximum of three hours in reading (68.9%) in the second stage, obtaining in the third stage RA of 43.4, 32,1 and 64% in 7th, 10th and 14th days of evaluations, when compared to the GIV and obtaining similar values of the group not incised vehicle (GNIV) on 14 dayth. In the von Frey and Hargreaves GNIV showed similar readings in the three stages of the experiment. The DHP (10mg/kg) did not alter the motor activity of mice in rota-rod test. Whereas the compound DHP showed antinociceptive activity in writhing test, antiedematogenic in ear edema, inhibited the 2nd phase of nociception (inflammatory pain) in formalin test and leukocyte migration, promoting reversal of hypernociception in models of thermal hyperalgesia and allodynia mechanics, these results indicate that the effectiveness of DHP involves the participation of anti-inflammatory mechanisms and create favorable outlook for its future use with this therapeutic goal. / A inflama??o ? um processo fisiol?gico de resposta org?nica diante de les?o tissular ou infec??o, gerando a dor como caracter?stica constante. Os compostos piraz?licos s?o drogas de origem sint?tica com um anel pirazol?nico na sua estrutura qu?mica, com os quais diversos estudos demonstram a efic?cia no controle da dor, da febre e da inflama??o. A necessidade do desenvolvimento de novos f?rmacos com propriedades analg?sicas e anti-inflamat?rias, de baixo custo e que apresentem poucas rea??es adversas, tem estimulado a s?ntese e o estudo das atividades farmacol?gicas dos compostos piraz?licos. Com esse objetivo, foi estudado o potencial antinociceptivo e anti-inflamat?rio do composto piraz?lico 1,5-difenil-3-hidrazinopirazol(a) (DHP), administrado pela via oral, nos modelos farmacol?gicos das contor??es abdominais pelo ?cido ac?tico, tail-flick, formalina, edema de orelha induzido pelo ?leo de cr?ton e peritonite induzida pela carragenina em camundongos; e na alodinia mec?nica (von Frey) e hiperalgesia t?rmica (Hargreaves) em ratos. A administra??o do DHP (1, 3 e 10mg/kg) diminuiu de maneira dose-dependente (41,3, 62,7 e 76%) o numero de contor??es abdominais (ID50=1,3mg/kg). No teste de tail-flick, DHP (10mg/kg) n?o foi efetivo e a aplica??o do controle positivo fentanil (200?g/kg, s.c.) ampliou a lat?ncia ao est?mulo t?rmico em at? 138%. Sem alterarem a 1? fase de nocicep??o (dor neurog?nica) do teste da formalina, o DHP (10mg/kg) e o controle positivo indometacina (10mg/kg, p.o.) inibiram a reatividade na 2? fase (dor inflamat?ria) em 40,9 e 48,7% respectivamente. Essa mesma dose do DHP reduziu em 54% o edema de orelha induzido pelo ?leo de cr?ton, assim como o controle positivo dexametasona (2mg/kg, s.c.) em 55.3%. Tamb?m de forma dose-dependente o DHP (3, 10 e 30 mg/kg) inibiu em 11,8, 39 e 53,7% respectivamente, a migra??o de leuc?citos no teste da peritonite induzida pela carragenina (ID50=22,9mg/kg). Na avalia??o da alodinia mec?nica o grupo incisado tratado com o DHP (GIDHP - 10mg/kg) apresentou significativas revers?es da alodinia (RA) ap?s uma hora da administra??o, com RA m?xima na leitura de 12 horas (28,2%) na segunda etapa, mantendo-se na terceira etapa com RA de 26,9, 43,4 e 60,4% nos 7?, 10? e 14? dias de experimenta??o, comparados com o grupo incisado ve?culo (GIV). Na hiperalgesia t?rmica o GIDHP tamb?m produziu revers?o da hiperalgesia (RH) uma hora ap?s o tratamento, com RH m?ximo na leitura de 3 horas (68,9%) na segunda etapa, mantendo-se na terceira etapa com RH de 43,4, 32,1 e 64% nos 7?, 10? e 14? dias de experimenta??o, quando comparados ao GIV e obtendo valores semelhantes ao grupo n?o incisado ve?culo (GNIV) no 14? dia. No von Frey e no Hargreaves o GNIV apresentou leituras semelhantes nas tr?s etapas do experimento. O DHP (10mg/kg) n?o alterou a atividade motora de camundongos no teste do rota-rod. Considerando que o composto DHP apresentou atividade antinociceptiva no teste das contor??es, antiedematog?nica no edema de orelha, inibiu a 2? fase de nocicep??o (dor inflamat?ria) do teste da formalina e a migra??o leucocit?ria, promovendo ainda revers?o da hipernocicep??o nos modelos de hiperalgesia t?rmica e alodinia mec?nica; esses resultados indicam que a efetividade do DHP envolve a participa??o de mecanismos anti-inflamat?rios e criam perspectivas favor?veis para sua futura utiliza??o com esse objetivo terap?utico.