The present studies used the classical method of serial transections of the neuraxis to examine the neural mechanisms of injury-produced pain and morphine analgesia in the formalin test. The results showed that the behavioral response that follows formalin injection is complete within the brainstem, whereas telencephalic structures are critical for morphine to produce analgesia. In contrast, when the tail flick test, a model of noninjurious pain was used, both the behavioral response, and analgesia, were intact in the brainstem transected rat, in keeping with the current model of analgesia for this test. Brain areas classically associated with pain processing were not sufficient for morphine to produce analgesia in the formalin test. Instead, the amygdala, part of the emotion-mediating limbic system, was critical. It is argued that the formalin test may be a model of "dissociative" analgesia, in which reduction of the negative affective consequences of the pain plays a major role.

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Title page, table of contents and abstract only. The complete thesis in print form is available from the University of Adelaide Library. / While opioids are the most effective and widely used class of drug for the management of moderate to severe pain, their use may be limited by adverse effects that are unpleasant and potentially dangerous. Research is increasingly directed towards strategies to improve the use of opioids in pain management, investigating methods by which the analgesia afforded by an opioid may be enhanced, while minimising adverse effects. One approach that has produced promising findings in animal studies and some clinical reports is the combination of an opioid agonist and "ultra-low" (nanomole) doses of an opioid antagonist. A recent animal study reported that antinociception may be significantly enhanced with the combination of the partial opioid agonist/antagonist buprenorphine and ultra-low doses of the antagonist naloxone. The central aim of the studies described herein was to investigate the effect of this drug combination on response to experimental nociceptive stimuli and the incidence and severity of adverse effects among healthy volunteers. The first study established normative responses to two commonly used nociceptive tests, the cold pressor and electrical stimulation tests, in 100 healthy volunteers. The effect of buprenorphine on nociceptive test performance had not previously been determined, therefore a dose-ranging study of buprenorphine was conducted to establish a doseresponse relationship. The subsequent two studies investigated the effect of a range of buprenorphine:naloxone IV dose ratios (5:1, 10:1, 12.5:1, 15:1, 20:1 and 25:1) on nociception and adverse effects among healthy volunteers. These studies are the first to investigate the combination of buprenorphine and ultra-low dose antagonist in humans, and the first to assess the agonist:antagonist combination in an experimental model of human nociception. Antinociception was significantly enhanced with the combination of buprenorphine and naloxone in the 12.5:1 and 15:1 ratios. Moreover, this enhanced antinociception occurred without a simultaneous increase in adverse effects and indeed with a reduction in the severity of some effects. An agent that produces greater analgesia and reduces adverse effects has the potential to overcome some of the barriers that limit the use of opioids in pain management. The current findings indicate that further investigation of this drug combination is warranted. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1177227 / Thesis (Ph.D.) -- University of Adelaide, Dept. of Clinical and Experimental Pharmacology, 2005

Thesis (B.A.)--Haverford College, Dept. of Psychology, 2006. / Includes bibliographical references.

Thesis (B.A.)--Haverford College, Dept. of Psychology, 2006. / "Based on an experiment by: Caryn Dolich, Emily Hurwitz, Sarah Nagle and Jeff Ratliff." Includes bibliographical references.

Thesis (Ph. D.)--University of Rhode Island, 2005. / Typescript. Includes bibliographical references (leaves 179-196).

Thesis (B.A.)--Haverford College, Dept. of Psychology, 2006. / Includes bibliographical references.

Resumo: O bloqueio interpleural foi inicialmente utilizado para analgesia nas cirurgias do abdome superior, colecistectomias abertas, esofagectomias, fraturas costais múltiplas, dor crônica e pancreatites. Esta técnica não se demonstrou satisfatória para analgesia nas toracotomias para pneumonectomia e lobectomia, o que é justificado pela perda da solução anestésica pelo dreno torácico, com consequente má distribuição desta na cavidade pleural. Todavia, nos procedimentos minimamente invasivos, como a simpatectomia torácica videoassistida, se demonstrou satisfatória e duradoura com redução do consumo de opióide no período pós-operatório, nestes procedimentos o anestésico é administrado no espaço interpleural sem riscos de pneumotórax ou injeção intravascular do fármaco. Entretanto, não são encontradas publicações que atestem segurança ou eficácia desta técnica. O objetivo deste estudo foi avaliar a eficácia, as alterações hemodinâmicas e ventilatórias, bem como os riscos de intoxicação por anestésico local decorrentes da analgesia interpleural bilateral com ropivacaína em pacientes com hiper-hidrose palmoaxilar submetidos à simpatectomia torácica videoassistida.Estudo duplo-cego, randomizado, incluindo 51 pacientes divididos em três grupos iguais: G1, G2 e G3 que receberam solução interpleural bilateral de solução fisiológica 20mL a 0,9%, de ropivacaína 20mL a 0,35% e de ropivacaína 20mL a 0,5%, respectivamente. Foram avaliados: PAS, PAD, PAM, FC, f, PaO2, PaCO2, SaO2, pH, PImáx, presença de náuseas e vômitos, concentração plasmática da ropivacaína, sinais e sintomas de intoxicação por anestésico local, escore de dor (ENV), localização e fatores desencadeantes da dor, necessidade de analgesia suplementar e satisfação dos pacientes.Os grupos foram homogêneos em relação aos dados demográficos e apresentaram comportamento estável... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The interpleural block was first used for analgesia of upper abdominal surgeries, open cholecystectomy, esophagectomies, multiple rib fractures, chronic pain and pancreatitis. This technique has not proved satisfactory while used in thoracotomy for lobectomy and pneumonectomy which may be justified by the loss of the anesthetic thru the chest tube resulting in poor distribution of it in the pleural cavity. While applied in minimally invasive procedures, such as video-assisted thoracic sympathectomy, the technique has been proved satisfactory and long lasting with postoperatively reduced opioid consumption. In these kinds of procedures the anesthetic is administered in the interpleural space without the risk of pneumothorax and intravascular injection of the drug. However, there are no publications found attesting safety or effectiveness of this technique. The aim of this study was to evaluate the hemodynamic and ventilatory changes, as well as the risks of intoxication by local anesthetic, when bilateral interpleural analgesia with ropivacaine is performed for axillary sympathectomy thoracoscopy due palmar hyperhidrosis.It is a double-blind study with 51 patients randomized in three groups: G1 (saline), G2 (0.35% ropivacaine) and G3 (0.5% ropivacaine). Each group received bilateral interpleural injection of 20ml of the designed solution. Were evaluated the following parameters: PAS, PAD, PAM, FC, f, PaO2, PaCO2, SaO2, pH, PImáx, presence of nausea and vomiting, plasma concentrations of ropivacaine, signs and symptoms of intoxication by local anesthetic, pain score (VAS), location and triggering factors of pain, need of rescue analgesia and patient satisfaction towards the analgesia technique.Both groups were homogenous towards demographic data and demonstrated stable hemodynamic, pH, PaO2 and SaO2 measures. It was noted, however, that G2 had raised f in the immediate postoperative... (Complete abstract click electronic access below) / Orientador: Guilherme Antonio Moreira de Barros / Coorientador: Daniele Cristina Catâneo / Banca: Norma Sueli Pinheiro Módolo / Banca: Geraldo Rolim Rodrigues Junior / Banca: Rosa Inês Pereira / Banca: Glória Maria Braga Potério / Doutor