Consists of twenty nine papers previously published in various journals. / Includes bibliographical references. / 1 v. (various pagings) : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Physical, chemical, and neurophysiological processes responsible for fabric-evoked discomfort, itch and prickle sensation, and skin rash are defined. / Thesis (M.D.)--University of Adelaide, Dept. of Physiology, 1995?

We investigated the role of two intracellular second messengers, extracellular signal-regulated protein kinase (ERK), and protein kinase C (PKC) in a model of persistent pain, using intrathecal (i.t) (R,S )-DHPG to induce spontaneous nociceptive behaviours (SNBs). SNBs were measured in animals that were treated with an ERK inhibitor (PD 98059), and a PKC inhibitor (GF 109203X) compared with controls. Mechanical allodynia, was measured using paw withdrawal thresholds in the von Frey test, and thermal hyperalgesia was measured using response latencies in the plantar test. In study 1, it was shown that spinal administration of PD 98059, dose-dependently decreased SNBs, and reduced mechanical allodynia and thermal hyperalgesia. In study 2, it was shown that i.t. pretreatment with the GF 109203X, reduced SNBs and thermal hyperalgesia, but not mechanical allodynia. These results suggest that both ERK and PKC are involved in SNBs and the concomitant and thermal hyperalgesia and possibly mechanical allodynia.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 7 uppsatser.

Thesis (Ph. D.)--University of Oklahoma. / Bibliography: leaves 62-71.

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No description available.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

A proteólise limitada de certas proteínas leva à liberação de peptídeos opióides endógenos. Vários relatos apontam que peptídeos derivados da hemoglobina como hemorfinas e hemopressinas têm efeito antinociceptivo, pela atividade de modulação de receptores acoplados a proteínas G. No presente estudo, um ensaio de captura do substrato (ECS) foi combinado com a marcação isotópica e LC-MS/MS para identificar e caracterizar um novo fragmento da hemoglobina que se liga à EP24.15. O peptídeo AGH, identificado neste trabalho, inibe respostas de hipernocicepção periféricas através de receptores opióides do tipo <font face=\"Symbol\">m . A persistência do peptídeo AGH no tecido nervoso perfundido sugere relevância fisiológica. Embora o AGH seja derivado de hemoglobina e tenha atividade opióide, falta-lhe a sequência chave das hemorfinas (YPWT), indicando que ele pode pertencer a uma nova classe de peptídeos derivados da hemoglobina. Adicionalmente, o AGH modula as interações entre as proteínas 14-3-3<font face=\"Symbol\">e e EP24.15 in vitro, podendo estar relacionado com a secreção não convencional da EP24.15. / Limited proteolysis of certain proteins leads to the release of endogenous opioid peptides. Several reports have shown that hemoglobin-derived peptides such as hemorphins and hemopressins have an antinociceptive effect by modulating GPCR activity. In the present study, a substrate capture assay (SCA) was combined with isotopic labeling and LC-MS/MS to identify and characterize a new bioactive hemoglobin fragment that binds to EP24.15. AGH, a new peptide identified in this work, inhibits peripheral hyperalgesic responses through <font face=\"Symbol\">m opioid receptors (MOR). The persistence of AGH peptide in perfused nervous tissue suggests its physiological relevance. Although AGH is derived from hemoglobin and it is a peptide with opioid activity, it lacks the key sequence of hemorphins (YPWT), indicating that it is part of a new class of peptides derived from hemoglobin. Additionally, the AGH modulates interactions between 14-3-3<font face=\"Symbol\">e and EP24.15 proteins in vitro and may be related to the unconventional EP24.15 secretion.