The objective of this study was to evaluate effects of extracorporeal shockwave therapy (ESWT) on spinal mechanical nociceptive threshold (MNT) and multifidus muscle cross-sectional area (CSA) in horses with thoracolumbar pain. We hypothesized that ESWT would increase MNT and multifidus CSA. Twelve horses with thoracolumbar pain were included. Prior to treatment, each thoracolumbar spine was radiographed to document existing pathology. Horses received 3 ESWT treatments, 2 weeks apart (days 0, 14, 28). Palpation scores were documented (days 0, 45, 65) and ultrasonographic CSA of left and right multifidus was recorded at T12, T14, T16, T18, L3 and L5 (days 0, 45, 65). MNT was measured at T12, T14, T16, T18, L3 and L5 every 7 days (day 0-56). Change in MNT in 10/12 horses was significant at each timepoint compared to day 0 (P<0.05). MNT increased at all timepoints at 6 sites in 2/12, at 5 sites in 3/12, at 4 sites in 4/12 and at 1 site in 1/12 (P<0.05). MNT average percent increase from day 0-56 was 64% for T12-T18 and 29% for L3-L5. There was no statistical difference in MNT from day 35-56 (P=0.25). A bimodal analgesic trend was observed following ESWT. Degree of radiographic change was not associated with response to treatment and no significant change in multifidus CSA was observed. In conclusion, 3 treatments of ESWT 2 weeks apart raised MNT over a 56-day period in horses with back pain, but did not influence change in CSA of the multifidus. / Master of Science / Back pain in the horse is a frequently diagnosed and treated cause of back stiffness, lameness, poor performance and/or avoidance behavior under saddle. Treatment is focused on reducing pain and inflammation and on strengthening and promoting proper muscle development to maintain long term results. Recently, rehabilitation of the deep spinal stabilizer multifidus muscle, particularly with regard to increased cross-sectional area (CSA), has become a focus of targeted physiotherapy. Assessment of the degree of pain is subjective due to individual interpretation and palpation technique. In an attempt to standardize quantification of pain, pressure algometry has become a validated, objective and repeatable measure of axial skeleton mechanical nociceptive threshold (MNT), which is defined as the minimum pressure required to induce a pain response. Although many treatment options for back pain exist, there is limited research documenting the efficacy of these treatments in horses. Extracorporeal shockwave therapy (ESWT), which consists of focused, high velocity acoustic waves, is one type of non-invasive, well-tolerated treatment for back pain. Despite its popularity, there is no research documenting the effects of ESWT on equine spinal MNT or multifidus muscle CSA. This is the first study to document the effects of ESWT on spinal MNT and multifidus muscle CSA in horses with back pain. We hope that the results of this study will help guide treatment decisions for horses with back pain.

Orientador: Stelio Pacca Loureiro Luna / Banca: Francisco José Teixeira Neto / Banca: Yara Cury / Resumo: O objetivo do estudo foi avaliar e comparar um analgesiômetro de estimulação nociceptiva mecânica a um de estimulação nociceptiva térmica. Para tal, foi desenvolvido um modelo experimental de determinação do limiar nociceptivo mecânico (LNM), que envolveu a produção de um foco inflamatório para avaliar os efeitos analgésicos dos antiinflamatórios não esteróides (AINES) em gatos. Oito gatos adultos castrados, pesando entre 3,4l0,6kg, foram utilizados num estudo cruzado e aleatório. O estímulo nociceptivo mecânico foi realizado por meio de um bracelete de plástico, adaptado de um manguito de pressão neonatal, colocado ao redor do antebraço e contendo três pinos de 2,4mm de diâmetro. O manguito foi inflado até a reação do animal, que foi considerado como o LNM. O estímulo nociceptivo térmico (LNT) foi realizado por meio de um dispositivo justaposto a um manguito de pressão neonatal, posicionado ao redor do tórax por uma cinta elástica. O elemento de calor era acionado e a temperatura elevada em 0,6oC/s. O estímulo foi interrompido assim que o animal reagiu. O estudo foi cego e dividido em duas fases. Na primeira, após quatro mensurações basais dos LNT e LNM, cada gato recebeu pela via SC, buprenorfina (0,01mg/kg), carprofeno (4mg/kg) ou solução fisiológica (0,3mL) em um estudo de três períodos, com uma semana de intervalo. As mensurações foram feitas aos 15, 30, 45min e 1,2,3,4,6,8 e 24h, após cada tratamento. Na segunda fase, os gatos foram anestesiados com isofluorano para a injeção intradérmica de kaolin no antebraço, para produção de um foco inflamatório. No dia 0, às -3hr, cada gato recebeu pela via subcutânea, 0,3 ml de solução fisiológia 0,9% (GS e GB) ou 4 mg/kg de carprofeno (GC)... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The aim of this study was to evaluate a prototype pressure stimulus device for cats and to compare with a known thermal threshold device. An objective model of nociceptive threshold determination on a site of mild inflammation was developed for evaluation of NSAID analgesia in cats. Eight healthy adult cats weighing between 3.0 and 4.9 kg were used in a randomized crossover study. Pressure stimulation was performed via a plastic bracelet taped around the forearm. Three 2.4mm diameter ball-bearings, in a 10mm triangle, were advanced against the craniolateral surface of the antebrachium by manual inflation of a modified blood pressure bladder. Pressure in the cuff was recorded as threshold (PT) at the behavioral end point (lifting, turning towards, leg shake and head turn). Thermal threshold (TT) was tested as previously reported by Dixon et al. (2002). Stimuli were stopped if they reached 55°C or 650mmHg without response. The study was divided in two phases. In both phases, the investigator was blinded to the treatment. In the first phase, after four pressure and thermal threshold baseline measurements, each cat received SC buprenorphine 0.01mg/kg, carprofen 4 mg/kg or saline 0.3mL in a three period study with one week interval. Measurements were made at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8 and 24h, after injection. In the second phase, cats were anaesthetized with isoflurane and at 0h, kaolin (0.15ml of 5% suspension at 5 sites) was injected intradermally at the testing site on the forelimb to produce mild inflammation. In control treatment (SG), at -3h, cats received physiological saline (0.3ml, SC) and three baseline pressure thresholds in the forearm were recorded before cats received another injection of a similar volume at -1h... (Complete abstract, access undermentioned electronic address) / Mestre

Made available in DSpace on 2014-06-11T19:27:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-02-09Bitstream added on 2014-06-13T19:14:54Z : No. of bitstreams: 1 steagall_pvm_me_botfm.pdf: 548034 bytes, checksum: 9a8da28f5fb380f73f0c1d4a2494de63 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O objetivo do estudo foi avaliar e comparar um analgesiômetro de estimulação nociceptiva mecânica a um de estimulação nociceptiva térmica. Para tal, foi desenvolvido um modelo experimental de determinação do limiar nociceptivo mecânico (LNM), que envolveu a produção de um foco inflamatório para avaliar os efeitos analgésicos dos antiinflamatórios não esteróides (AINES) em gatos. Oito gatos adultos castrados, pesando entre 3,4l0,6kg, foram utilizados num estudo cruzado e aleatório. O estímulo nociceptivo mecânico foi realizado por meio de um bracelete de plástico, adaptado de um manguito de pressão neonatal, colocado ao redor do antebraço e contendo três pinos de 2,4mm de diâmetro. O manguito foi inflado até a reação do animal, que foi considerado como o LNM. O estímulo nociceptivo térmico (LNT) foi realizado por meio de um dispositivo justaposto a um manguito de pressão neonatal, posicionado ao redor do tórax por uma cinta elástica. O elemento de calor era acionado e a temperatura elevada em 0,6oC/s. O estímulo foi interrompido assim que o animal reagiu. O estudo foi cego e dividido em duas fases. Na primeira, após quatro mensurações basais dos LNT e LNM, cada gato recebeu pela via SC, buprenorfina (0,01mg/kg), carprofeno (4mg/kg) ou solução fisiológica (0,3mL) em um estudo de três períodos, com uma semana de intervalo. As mensurações foram feitas aos 15, 30, 45min e 1,2,3,4,6,8 e 24h, após cada tratamento. Na segunda fase, os gatos foram anestesiados com isofluorano para a injeção intradérmica de kaolin no antebraço, para produção de um foco inflamatório. No dia 0, às -3hr, cada gato recebeu pela via subcutânea, 0,3 ml de solução fisiológia 0,9% (GS e GB) ou 4 mg/kg de carprofeno (GC)... / The aim of this study was to evaluate a prototype pressure stimulus device for cats and to compare with a known thermal threshold device. An objective model of nociceptive threshold determination on a site of mild inflammation was developed for evaluation of NSAID analgesia in cats. Eight healthy adult cats weighing between 3.0 and 4.9 kg were used in a randomized crossover study. Pressure stimulation was performed via a plastic bracelet taped around the forearm. Three 2.4mm diameter ball-bearings, in a 10mm triangle, were advanced against the craniolateral surface of the antebrachium by manual inflation of a modified blood pressure bladder. Pressure in the cuff was recorded as threshold (PT) at the behavioral end point (lifting, turning towards, leg shake and head turn). Thermal threshold (TT) was tested as previously reported by Dixon et al. (2002). Stimuli were stopped if they reached 55°C or 650mmHg without response. The study was divided in two phases. In both phases, the investigator was blinded to the treatment. In the first phase, after four pressure and thermal threshold baseline measurements, each cat received SC buprenorphine 0.01mg/kg, carprofen 4 mg/kg or saline 0.3mL in a three period study with one week interval. Measurements were made at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8 and 24h, after injection. In the second phase, cats were anaesthetized with isoflurane and at 0h, kaolin (0.15ml of 5% suspension at 5 sites) was injected intradermally at the testing site on the forelimb to produce mild inflammation. In control treatment (SG), at -3h, cats received physiological saline (0.3ml, SC) and three baseline pressure thresholds in the forearm were recorded before cats received another injection of a similar volume at -1h... (Complete abstract, access undermentioned electronic address)

Selon l’Association Internationale pour l’Étude de la Douleur, la douleur neuropathique est causée par « une lésion ou une maladie du système somatosensoriel ». Actuellement, il n’existe pas de test permettant de la diagnostiquer avec certitude. En médecine humaine, les suspicions cliniques reposent essentiellement sur les caractéristiques de la douleur perçue par le patient. En effet, le mélange de douleurs lancinantes et fulgurantes souvent de très forte intensité, et les termes utilisés pour les décrire, permettent de poser un diagnostic présomptif. En revanche, chez les personnes non-communicantes ainsi que chez nos patients en médecine vétérinaire, la douleur neuropathique devient extrêmement difficile à déceler. Elle pose aussi un problème éthique puisque ces douleurs sont souvent qualifiées d’insoutenables et sont notoirement réfractaires aux traitements analgésiques conventionnels. Faute de données spécifiques, le Conseil sur la douleur de l’Association internationale des vétérinaires pour les animaux de compagnie (WSAVA Global Pain Council) base ses recommandations thérapeutiques sur des succès anecdotiques relevés dans des rapports de cas ou des données tirées de la médecine humaine. Notre étude s’articulait autour de trois objectifs principaux : 1) Évaluer la fiabilité et la faisabilité des tests proposés pour explorer les profils somatosensoriels chez des chiens de propriétaires, incluant une nouvelle méthode dynamique permettant d’évaluer le système endogène de modulation de la douleur ; 2) Identifier une population de chiens de propriétaires présentant de la douleur neurologique chronique à composante neuropathique d’apparition spontanée, en se basant sur les recommandations données en médecine humaine, et caractériser la douleur neuropathique dans ce groupe, en comparant les profils somatosensoriels et les concentrations en cytokines inflammatoires de ces chiens avec ceux d’un groupe contrôle ; 3) Suivre l’évolution des profils somatosensoriels, des concentrations en cytokines inflammatoires et des scores de douleur/qualité de vie des chiens neuropathiques enrôlés dans un essai clinique croisé prospectif, partiellement masqué et randomisé, afin d’évaluer les effets du placebo, du gabapentin seul ou administré en combinaison avec le méloxicam sur ces paramètres. Nos hypothèses étaient que la méthodologie proposée serait fiable et faisable pour évaluer les profils somatosensoriels chez les chiens de propriétaires, et que la population de chiens souffrant de douleur neuropathique diffèrerait du groupe contrôle par leurs concentrations en cytokines inflammatoires, leurs seuils nociceptifs et leur capacité à moduler la douleur après application d’un stimulus conditionnant. Enfin, il était attendu que les traitements actifs (gabapentin et gabapentin-méloxicam) altèreraient les profils somatosensoriels, les scores de douleur/qualité de vie et les concentrations en cytokines inflammatoires des patients neuropathiques. Les tests quantitatifs sensoriels retenus pour évaluer la population de chiens neuropathiques dans la seconde partie du projet (stimulations mécanique et électrique) étaient fiables, faciles à réaliser et bien tolérés. L’évaluation du système inhibiteur descendant induit par les stimulations nociceptives (système endogène de modulation de la douleur; DNIC) a permis de mettre en évidence une dysfonction de la capacité de modulation de la douleur chez les chiens neuropathiques. L’administration de gabapentin combiné ou non avec le méloxicam a eu pour effet de « normaliser » les profils somatosensoriels dynamiques (augmentation du nombre de chiens présentant une inhibition après l’application d’un stimulus conditionnant). Les scores de douleur/qualité de vie ont évolué en faveur d’une amélioration avec l’administration de gabapentin seul ou en combinaison avec le méloxicam. Les concentrations en cytokines inflammatoires et les profils somatosensoriels statiques (les seuils nociceptifs), quant à eux, n’étaient pas différents entre les groupes et n’ont pas significativement varié avec les traitements étudiés. À travers ces études, nous avons présenté de nouvelles techniques de QST fiables et faisable chez le chien. Nous avons également montré que l’évaluation du DNIC est possible dans l’espèce canine, et que les chiens présentant une douleur chronique à composante neuropathique ont un DNIC déficient. L’évaluation des profils somatosensoriels dynamiques et des scores de douleur/qualité de vie supportent l’utilisation du gabapentin seul ou en combinaison avec le méloxicam pour le traitement médical de la douleur neuropathique chez le chien, tel que recommandé par les spécialistes du WSAVA. / According to the International Association for the Study of Pain, neuropathic pain is caused by "a lesion or a disease of the somatosensory system". Currently, there is no definitive test available to diagnose neuropathic pain. In humans, the presumptive diagnosis is essentially based on the characteristics of the pain perceived by the patient. In non-communicative individuals, on the other hand, just like in our patients in veterinary medicine, the diagnosis of neuropathic pain is difficult and poses an ethical problem because this type of pain is often qualified as unbearable and known to be refractory to conventional therapies. In the absence of specific data, the Global Pain Council of World Small Animal Veterinary Association (WSAVA) based its treatment recommendations of neuropathic pain on anecdotal veterinary reports, case reports or data from human medicine. This PhD program had three main objectives: 1) To assess the reliability and feasibility of the tests proposed to explore the somatosensory profiles in client-owned dogs, including a method to assess the descending noxious inhibitory controls; 2) To identify a population of client-owned dogs with naturally-occurring neuropathic pain, based on the recommendations from human medicine ; and to characterize neuropathic pain in this group, by comparing the somatosensory profiles and the serum levels of inflammatory cytokines of these dogs with those of a control group; 3) To determine the effects of placebo, gabapentin alone or in combination with meloxicam on the somatosensory profiles, concentrations of inflammatory cytokines and pain scores of dogs with naturally-occurring neuropathic pain managed medically, in a prospective, partially masked and randomized crossover clinical trial. Our hypotheses were that the proposed methodology would be feasible and reliable, allowing to assess somatosensory profiles of client-owned dogs, and that dogs with neuropathic pain would differ from the control group in their serum concentrations of inflammatory cytokines, their nociceptive thresholds and their ability to modulate pain after the application of a conditioning stimulus. Gabapentin and gabapentin-meloxicam would change somatosensory profiles, pain scores and serum concentrations of inflammatory cytokines of dogs with neuropathic pain. 7 The quantitative sensory tests (electrical and mechanical stimulations) were easy to perform, well tolerated and reliable. The evaluation of the diffuse noxious inhibitory control (endogenous pain modulation system; DNIC) revealed a dysfunction of the pain modulation capacity in neuropathic dogs. Administration of gabapentin with or without meloxicam had a "normalizing" effect on the dynamic somatosensory profiles (increase in the number of dogs showing inhibition after application of a conditioning stimulus). Pain / quality of life scores improved after gabapentin alone or in combination with meloxicam. On the other hand, serum concentrations of inflammatory cytokines and static somatosensory profiles (nociceptive thresholds) were not different between groups and did not vary significantly with treatments. Through these studies, we have presented new reliable and feasible QST techniques in dogs. We have also shown that the evaluation of the DNIC is possible in the canine species, and that dogs with chronic pain with a neuropathic component have a deficient DNIC. The assessment of the dynamic somatosensory profiles and pain / quality of life scores support the use of gabapentin alone or in combination with meloxicam for the medical management of neuropathic pain in dogs, as recommended by WSAVA specialists.

Made available in DSpace on 2014-07-29T15:13:42Z (GMT). No. of bitstreams: 1 Tese fim.pdf: 2195590 bytes, checksum: d021e1bbfb36f512ab5f6d127c5908e1 (MD5) Previous issue date: 2011-03-25 / Tramadol is an analgesic with action of opioids and non-opioid receptors, which acts by promoting activation of central inhibitory mechanisms of pain. In the last decade, there was a significant advance in research related to the use of tramadol in horses. There is evidence that the drug has significant analgesic effect in horses through mechanisms unclear. The aim of this study was to evaluate clinical and cardiorrespiratory effects and mechanical nociceptive threshold of tramadol, administered intravenously in horses. Moreover, we assessed also the effects of preemptive administration of tramadol on the clinical effects and post-incisional mechanical hyperalgesia. In the first study, seven adult horses were used in a three-way crossover study design in which tramadol was intravenous administered at 1mg kg-1, 2mg kg-1 e 3mg kg-1. Heart rate, respiratory rate, rectal temperature, systolic arterial pressure, diastolic arterial pressure, mean arterial pressure, intestinal motility, head height and behavioral change were recorded before and during 180 minutes after treatment. Mechanical nociceptive threshold from these points were averaged to obtain mean values at each time with von Frey electronic analgesiometer, applying a force in a hoof. Compared to others treatments, the horses that received 3mg kg-1 showed significant increases in respiratory rate and more pronounced behavioral changes. In horses treated with 1mg kg-1, there was a significant decrease in respiratory rate and more pronounced behavioral changes. Motility scores showed transitory decreased in horses treated with 2 mg kg-1. The tramadol did not caused changes in mechanical nociceptive threshold regardless of treatment. In conclusion, the tramadol at doses evaluated produced minimal transient side effects or clinical changes. However has no antinociceptive effect in a model of mechanical stimulus. In a second study, ten horses were divided in two groups. The horses were treated IV with a single dose of 2 mg kg-1 of tramadol (TG) or with a similar volume of sterile water (SG). Heart rate, respiratory rate, rectal temperature, systolic arterial pressure, diastolic arterial pressure, mean arterial pressure, intestinal motility, and behavioral change were recorded before and during 48 hours after treatment. Mechanical nociceptive threshold was measured by von Frey electronic analgesiometer in post-incisional model. To study, a skin incision was made over the thigh region. Compare to saline, tramadol caused transitory increased in mean and diastolic arterial pressure in first hour after treatment. The tramadol was able to decrease a remained time of primary hyperalgesia, but not prevented its appearance in compared to SG. In the global range score no changes were observed between groups along the moments. / O tramadol é um fármaco analgésico com ação em receptores opioides e não opioides, que atua promovendo ativação central dos mecanismos inibitórios da dor. Na última década, houve significativo avanço em pesquisas relacionadas ao seu emprego em equinos. Há indícios de que o fármaco possua efeito analgésico considerável nessa espécie por mecanismos ainda não completamente esclarecidos. Diante disso, os objetivos deste trabalho foram: avaliar os efeitos clínicos e o potencial antinociceptivo mecânico de três diferentes doses de tramadol, administradas por via intravenosa em equinos e os efeitos da administração preemptiva do tramadol sobre as variáveis clínicas e hiperalgesia mecânica pós-incisional. No primeiro estudo sete equinos adultos foram tratados com 1mg/kg, 2mg/kg ou 3mg/kg de cloridrato de tramadol, via intravenosa em três ocasiões distintas. Os parâmetros avaliados foram frequência cardíaca (FC), frequência respiratória ( f ), temperatura retal (TR), pressões arteriais sistólica (PAS), diastólica (PAD) e média (PAM), intensidade de sedação verificado pela medida de altura da cabeça (AC), motilidade intestinal (MI), alterações comportamentais e o limiar nociceptivo mecânico (LNM), empregando-se estímulo mecânico na coroa do casco, com analgesímetro digital de von Frey. Os animais tratados com 3mg/kg apresentaram aumento significativo na frequência respiratória, além de alterações comportamentais mais acentuadas em comparação aos demais tratamentos. Em relação à pressão arterial, houve aumento significativo no grupo tratado com 1mg/kg. Houve redução transitória nos escores de avaliação da MI, principalmente nos animais tratados com 2mg/kg. O tramadol, nas doses administradas, não apresentou potencial antinociceptivo capaz de desencadear mudanças no LNM em equinos. Diante dos resultados, conclui-se que as alterações clínicas observadas nas diferentes doses foram consideradas discretas e transitórias, especialmente na dose de 2mg/kg. No modelo de avaliação adotado, o tramadol não apresentou potencial antinociceptivo mecânico em nenhuma das doses avaliadas. No segundo estudo, dez equinos foram distribuídos em dois grupos, sendo o GT tratado com 2mg/kg de cloridrato de tramadol em solução a 1% e o GS tratado com solução salina, via intravenosa. Avaliaram-se FC, f, PAS, PAD, PAM, traçado eletrocardiográfico, TR, MI e LNM, empregando modelo incisional e analgesímetro digital de von Frey. Neste estudo, os animais do GT apresentaram aumento transitório na PAM e PAD, durante a primeira hora. Quanto ao LNM, o grupo GT apresentou redução no tempo de permanência de hiperalgesia primária quando comparado ao GS. Entretanto, a administração prévia não foi capaz de inibir seu desencadeamento. Ao comparar as médias globais do lado incisado entre o GS e o GT, não houve alteração significativa na força empregada em nenhum momento avaliado. Diante dos resultados, conclui-se que alterações clínicas observadas na dose de 2 mg/kg de tramadol foram consideradas transitórias e sem relevância clínica e que, no modelo de avaliação empregado, o tramadol não foi capaz de impedir o desencadeamento tanto de hiperalgesia primária quanto secundária.