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There is an unmet medical need for the efficient treatment of neuropathic pain, a condition that affects approximately 10% of the population worldwide. Current therapies need to be improved due to the associated side effects and lack of response in many patients. Moreover, neuropathic pain causes great suffering to patients and puts an economical burden on society. The work presented in this thesis addresses SP1-7, (Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH), a major metabolite of the pronociceptive neuropeptide Substance P (SP). SP is released in the spinal cord following a noxious stimulus and binds to the NK1 receptor. In contrast to SP, the degradation fragment SP1-7 is antinociceptive through binding to specific binding sites distinct from the NK1 receptor. The aim of this thesis was to investigate the impact of SP1-7 on neuropathic pain. To understand how SP1-7 exerts its effect, a series of N-truncated forms of the heptapeptide were biologically evaluated. A set of small high-affinity ligands was evaluated in animal models of neuropathic pain. To confirm a clinical relevance the levels of SP1-7 in human neuropathic pain were assessed incerebrospinal fluid (CSF) collected from neuropathic pain patients. The results showed that SP1-7 could alleviate thermal as well as mechanical hypersensitivity in three different animal models of neuropathic pain. C-terminal amidation was connected with increased efficacy. N-terminal truncation of SP1-7 indicated a necessity of five amino acids in order to retain biological effect. One small high-affinity ligand showed a significant anti-allodynic effect. CSF levels of SP1-7 in neuropathic pain patients were lower compared to controls. Taken together, these findings demonstrate that the formation of SP1-7 may be attenuated in neuropathic pain. C-terminal amidation and a majority of its amino acids are necessary for stability and permeability. Clearly, SP1-7 and SP1-7 mimetics with high affinity to the SP1-7 binding site ameliorate neuropathic pain-like behaviors in animal models of neuropathic pain. Overall, the findings presented in this thesis contribute to new knowledge regarding the role of SP1-7 and related analogues and fragments in neuropathic pain. In a future perspective, this could be essential for the development of efficient strategies for managing patients with neuropathic pain.

The objective of this study was to: (1) model the course of the lingual nerve (LN) in the third molar region using digitized data and (2) investigate landmarks to aid in predicting the position of LN. A MicroScribe 3-DX digitizer and Autodesk® Maya® 8.5 were used to create 3-D in-situ models of LN for seven human cadaveric specimens. Regression analysis demonstrated that an anteriorly positioned lingula is directly proportional to the vertical distance of the LN relative to the alveolar crest (p < 0.05). A superiorly positioned mylohyoid ridge was also directly proportional to the vertical distance of the LN relative to the alveolar crest (p < 0.05). The LN is positioned closer to the alveolar crest in specimens where the mylohyoid ridge is positioned superiorly (p = 0.001). This study demonstrated a novel way of quantifying the relative position of the LN using 3-D computer modeling.

The objective of this study was to: (1) model the course of the lingual nerve (LN) in the third molar region using digitized data and (2) investigate landmarks to aid in predicting the position of LN. A MicroScribe 3-DX digitizer and Autodesk® Maya® 8.5 were used to create 3-D in-situ models of LN for seven human cadaveric specimens. Regression analysis demonstrated that an anteriorly positioned lingula is directly proportional to the vertical distance of the LN relative to the alveolar crest (p < 0.05). A superiorly positioned mylohyoid ridge was also directly proportional to the vertical distance of the LN relative to the alveolar crest (p < 0.05). The LN is positioned closer to the alveolar crest in specimens where the mylohyoid ridge is positioned superiorly (p = 0.001). This study demonstrated a novel way of quantifying the relative position of the LN using 3-D computer modeling.

Made available in DSpace on 2016-06-02T20:18:11Z (GMT). No. of bitstreams: 1 2133.pdf: 3477721 bytes, checksum: f34adaf38055f1196a4ab12f47e94877 (MD5) Previous issue date: 2008-10-16 / Universidade Federal de Minas Gerais / Recovery denervated skeletal muscles is a challenge to rehabilitation. The degenerative changes on muscle tissue due to denervation cause muscle fiber atrophy and force generating incapacity impairing the individual daily life activities. Design strategies to treat denervated muscles are important to Physical Therapy. Electrical stimulation (ES) is a resource largely recommended to treat denervated muscles in humans, nevertheless, its effects and mechanisms on muscle adaptation are unclear. The aim of this thesis was to evaluate the effects of ES, applied as used in clinical-like situations, e.g., during single sessions, using surface electrodes and considering the changes in muscle excitability, on the denervated skeletal muscle adaptation in rat. The characterization of the muscle excitability pattern was used to choose the best electrical parameters. Histochemistry and immunohistochemistry tecnics were used to verify the morphology of denervated muscles submitted to ES. Furthermore, the real time polymerase chain reaction (PCR) analysis was used to evaluate the expression of important muscular genes, such as myoD, atrogin-1, metalloproteinase-2 and myostatin. ES was able to regulate many genes on rat denervated muscles; however ES neither avoid muscle fiber atrophy nor detain connective tissue proliferation in theses muscles. The results of this thesis have brought significative contributions to understand the mechanisms of ES, as recommended in rehabilitation, on denervated muscle. / Recuperar o músculo esquelético desnervado é um desafio para a reabilitação. As modificações degenerativas no tecido muscular decorrentes da desnervação causam atrofia das fibras musculares e perda na capacidade de geração de força prejudicando as atividades de vida diária do indivíduo. Desenvolver estratégias de tratamento destes músculos é importante para a Fisioterapia. A estimulação elétrica (EE) é um recurso amplamente utilizado no tratamento de músculos desnervados em seres humanos, contudo seus efeitos e mecanismos de atuação sobre a adaptação muscular ainda não são claros. O objetivo desta tese foi avaliar os efeitos da EE, aplicada como recomendada na prática clínica, isto é, em sessões de tratamento, usando eletrodos de superfície e considerando as alterações de excitabilidade muscular, sobre a adaptação do músculo esquelético desnervado em ratos. A caracterização do padrão de excitabilidade muscular foi utilizada para a escolha dos parâmetros elétricos. Técnicas de histoquímica e imunohistoquímica foram usadas para averiguar a morfologia dos músculos desnervados submetidos ao tratamento elétrico. Além disso, a análise da reação em cadeia de polimerase (PCR) em tempo real foi utilizada para avaliar a expressão de importantes genes musculares, como myoD, atrogina-1, metaloproteinase-2 de matriz e miostatina. A EE é capaz de regular a expressão de diversos genes no músculo desnervado de rato, contudo ela não detém a atrofia das fibras musculares e nem impede a proliferação de tecido conjuntivo nestes músculos. Os resultados desta tese trouxeram significativa contribuição para o entendimento dos mecanismos de ação da EE, como preconizado na reabilitação, sobre o músculo desnervado.

Made available in DSpace on 2015-03-26T13:46:55Z (GMT). No. of bitstreams: 1 texto completo.pdf: 1938194 bytes, checksum: 146a5d9b11aed10c03d5037d31ad5c74 (MD5) Previous issue date: 2010-12-14 / Fundação de Amparo a Pesquisa do Estado de Minas Gerais / Laser irradiation is frequently used as treatment for many pathologies of skeletal muscle, including peripheral nerves lesion. Therefore, the aim of this research was to evaluate by clinical and morfometric analysis the effects of laser therapy on neural and muscle repair after crushing of sciatic nerve and hind limb unloading. 48 Wistar male rats machos, with 60 days old, were divided in three groups with 16 animals each, and they were performed as one control group (GA) and two irradiated groups (GB with 4 J/cm² dose; GC with 6 J/cm² dose). After the sciatic nerve was crushed animals were maintained under hind limb suspension and received laser (GaAlAs) irradiation three times per week, during 14 or 28 days. The sciatic functional index (SFI) were measured before surgery, at 14 and 28 days, recovery was observed in all groups especially to GA at 28 days. Morfometric analysis of the nerve showed that the nerve recovery was better to the treated groups, specially at 14 days. The muscle morfometric analysis weren&#8217;t effected by laser therapy. Taken together the results allowed to conclude that laser therapy promotes morphological recover of the nerve, specially until 14 days. Yet laser isn&#8217;t able to influence the muscle recovery and function. / A irradiação com o laser é muito empregada para tratar uma variedade de condições patológicas do sistema músculo-esquelético, inclusive dos nervos periféricos. O objetivo desse trabalho foi avaliar por análises clínicas e morfométricas, a reparação neural e muscular após a compressão do nervo ciático de ratos submetidos à imobilização por suspensão e tratados ou não com diferentes doses de laser terapêutico. Foram utilizados 48 ratos machos, com idade de 60 dias, da raça Wistar, distribuídos em três grupos de 16 animais, sendo um utilizado como controle (GA) e outros dois que receberam diferentes doses do laser (GB com dose de 4 J/cm² e GC com dose de 6 J/cm²). Após a compressão do nervo ciático os animais foram submetidos à hipocinesia dos membros pélvicos e ao tratamento com Laser de GaAlAs três vezes por semana, durante 14 ou 28 dias. O índice funcional do ciático (IFC) foi avaliado nos períodos pré-operatório, aos 14 e aos 28 dias apresentando melhora para ambos os grupos, porém com destaque para o GA aos 28 dias. Os resultados da morfometria demonstraram que a recuperação do nervo foi melhor para os grupos tratados, principalmente aos 14 dias. Já os músculos não foram afetados pela laserterapia. A conclusão aponta para os benéficos da laserterapia sobre a recuperação morfológica do nervo ciático principalmente nos primeiros 14 dias após a lesão por axonotmese. Além de que a laserterapia, per si, não é capaz de influenciar a recuperação e a funcionalidade dos músculos acometidos.

Bakgrund: I Sverige rapporteras det årligen om patienter som drabbats av postoperativa trycksår och nervskador, till följd av felaktig positionering och/eller utesluten repositionering. Dessa komplikationer orsakar patienten onödigt lidande och förlängda vårdtider samt orsakar höga kostnader för sjukvården. Trots tidigare forskning som redogör för hur dessa komplikationer kan förebyggas saknas det ännu forskning om hur operationssjuksköterskans kunskaper är inom ämnet. Därmed är studien utförd för att undersöka och beskriva operationssjuksköterskans kunskaper idag utifrån ett stickprov bestående av några slumpmässigt utvalda sjukhus i Sverige. Syfte: Syftet med studien är att belysa operationssjuksköterskans kunskaper om positionering och repositionering för att förebygga postoperativa komplikationer, specifikt trycksår och nervskador. Metod: Studien utfördes som en empirisk tvärsnittsstudie med deskriptiv design och kvantitativ ansats där data samlades in via en egenutformad webbenkät. I studien deltog sju sjukhus i Sverige, vilket totalt resulterade i 137 enskilda deltagare. Resultat: Resultatet visade att dagens operationssjuksköterskor är intresserade av att få mer kunskap om preventivt arbete mot trycksår och nervskador. Det visade även en varierad åsikt om vem som besitter huvudansvaret för repositioneringen under operation. Slutsats: Deltagarna informerade om att de inte får regelbunden information inom ämnet från sin arbetsplats. Detta kan vara en av anledningarna till att repositionering inte utförs i den bemärkelsen som är rekommenderat enligt tidigare forskning. Det bör beslutas om vem som ska besitta huvudansvaret eller om det skall införas fasta rutiner för att därmed bidra till att patienten inte utsätts för onödigt lidande. / Background: Yearly in Sweden, patients are reported suffering from postoperative pressure ulcer and nerve damage due to incorrect positioning and/or excluded repositioning. These complications cause patient unnecessary suffering and extended time in care in the hospitals as well causes high costs for healthcare. Despite previous research which describes how these complications can be prevented, there is limited research on how the operating theatre nurse´s knowledge is on the subject. The study is conducted to investigate and describe today´s operating theatre nurses knowledge based on a sample of some randomly selected hospitals in Sweden. Aim: The aim of the study is to highlight the operating theatre nurse´s knowledge of positioning and repositioning to prevent postoperative complications, specifically pressure ulcers and nerve damage. Method: The study was conducted as an empirical cross-sectional study with descriptive design and quantitative approach where data was collected by a self-designed web questionnaire. In the study, seven hospitals in Sweden were participating, which resulted in 137 participants. Results: The results showed that today's theatre nurses are interested in gaining more knowledge about preventive work against postoperative complications, specific pressure ulcers and nerve injuries. It also showed a varied perception about who has the main responsibility for repositioning during surgery. Conclusion: Participants informed that they don´t receive regular information within the subject from their workplace. This may be one of the reasons why repositioning is not performed as recommended by previous research. It should be decided who should be in charge of the repositioning to prevent patients from unnecessary suffering.

A parestesia é um distúrbio neurosensitivo causado por uma lesão no tecido nervoso. Ela tem uma incidência pouco freqüente após as cirurgias de terceiros molares inferiores; no entanto para o cirurgião dentista é de grande relevância. A literatura comenta sobre os tipos de lesão nervosa, causas e alternativas de tratamento não conservadores ligados à neuromicrocirurgia que são relacionados nesses casos. Nesse trabalho procurou-se estabelecer a classificação da lesão ao nervo alveolar inferior que ocorre nas exodontias de terceiros molares inferiores, entender os mecanismos fisiológicos, as causas principais que levam à ocorrência desse distúrbio e estudar as técnicas de neuromicrocirurgia, com suas indicações e contra-indicações para os tipos de lesão nervosa. / Paresthesia consists of a neurosentitive disturb resulting from nerve tissue injury. It is less likely to occur following lower third molar surgeries, despite being highly relevant for dentists. The literature comments on the types of nerve injuries, its causes and related non-conservative treatment procedures involving neuromicrosurgery in such cases. This essay is an attempt to establish the types of nerve injury classification that occur following lower third molar surgery involving the inferior alveolar nerve, understand the physiological mechanisms, the main causes that result in such disturbance, and study the neuromicrosurgery procedures, their indications and non-indications concerning types of nerve injury.

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