Chronic pain may be defined as pain which persists in a patient for a prolonged period of time. Although this period of time may range from 3-12 months, it is most commonly described as pain which extends beyond the time required for healing. Chronic pain may also be classified into two different categories depending on the cause. The first category is nociceptive, which is chronic pain caused by activation of nociceptors. This may be due to several factors such as trauma or temperature. The second category is neuropathic chronic pain. These are chronic pains which are not necessarily caused by trauma, but more likely due to the malfunction of the nervous system. For this study, our aim is to develop a patient-controlled, externally actuated hydrogel system which is capable of ‘ON-OFF’ drug release. The model drug which was incorporated into the SAPD was a Non- Steroidal Anti-Inflammatory Drugs (NSAID), and thus our drug release system would be beneficial primarily for nociceptive chronic pain. This subcutaneously implanted SAPD is produced with an electroactive polymer which allows drug release in the presence of electrical stimulation. This would result in direct availability of drug at the site of actuation with reduced side-effects and increased drug bio-availability. The SAPD was formed by crosslinking polyvinyl alcohol (PVA) with diethyl acetamidomalate (DAA). The result was a hydrogel which was capable of swelling while remaining insoluble when placed in various solvents. After the hydrogel was synthesized, indomethacin was incorporated as the model drug. Indomethacin exhibited superior Drug Entrapment Efficiency (DEE) (±70-90%) and responsive release in the presence of an electrical stimulus. Finally, polyaniline (PANi) was used as the electroactive polymer in order to enhance the conductivity and allow sufficient release of the drug. Optimization of the SAPD was undertaken with a 3-factor Box-Behnken Design which measured the rate of erosion, drug release and DEE. The optimized SAPD was synthesized using PVA (0.8g) crosslinked with DAA (0.0689g) and a concentration of 1.3418%w/w PANi. Indomethacin was used and the DEE achieved was 76.32±10.46% (target 80.5381%). The drug release profile was 1.622%±0.1857% (target 1.7%) per release cycle and erosion rate was 5.73±1.26% (target 6.3201%) when actuated with a potential difference of 1V for a duration of 1 minute. Chemometric modelling performed on the SAPD showed that drug release may be attributed to erosion of the SAPD in the presence of an electrical stimulus. The polymeric strands usually rest as a coiled state within the SAPD. This coiled state may be the reason the hydrogel remained intact in the absence of electrical stimulation. However, external electrical fields may adduct to form a coil rather than an extended chain resulting in the formation of a globular aniline-vinyl complex. This formation thus leads to a weakened form of the hydrogel structure, resulting in breakdown and ultimately erosion. This erosive phenomenon ceased once the electrical stimulation was removed. The end result of this hydrogel erosion is the liberation of the entrapped indomethacin. In vivo animal studies on the SAPD indicated an ‘ON-OFF’ drug release profile. The drug release was consistent and drug quantity of ±0.15mg per release cycle in the Sprague-Dawley rat model. The SAPD was implanted subcutaneously under the left flank and an electrical stimulation was triggered with the use of a 2-in-1 galvano/potentiostat in order to ensure the electrical stimulus was constant. The potential difference used was 1V over a period of 1 minute. The rats were assessed for signs of illness or swelling after the implantation procedure to determine the biocompatibility of the SAPD. The rats were monitored for 10 days and weighed daily. Results have shown that the rats did not experience any considerable swelling and the weights of each rat were steady, thus indicating biocompatibility of the SAPD. Histopatholgical samples indicated mild inflammation around the site of implantation 10 days after implantation. This may have been due to minor surgery at site of implantation. The biocompatibility of the SAPD was generally good and there were no signs of tumour or long term tissue inflammation. Future application of the SAPD may include an external actuation device to be worn as a watch which allows actuation of the SAPD when required by the patient.

by Yiu-chung Wong. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1991. / Bibliography: leaves 171-184. / Acknowledgements --- p.i / Abstract --- p.iii / List of Figures --- p.1 / List of Tables --- p.4 / Chapter Chapter 1 - --- General Introduction --- p.6 / Chapter Chapter 2 - --- A Gas-liquid Chromatographic Method for Studying the Effect of Adrenaline on Venous Plasma Concentrations of Bupivaca- ine after Interpleural Administration --- p.41 / Chapter Chapter 3 - --- Gas-liquid Chromatographic Determination and Physicoche- mical Studies of Six Clinical Used Local Anaesthetics --- p.64 / Chapter Chapter 4 - --- Improved Gas-liquid Chromatographic Method for the Quant- itation of Plasma Pethidine and Norpethidine --- p.88 / Chapter Chapter 5 - --- Determination of Pethidine and Its Major metabolites in Hu- man Urine by Cas-liquid Chromatography --- p.112 / Chapter Chapter 6 - --- Plasma Protein Binding Characterization of Pethidine and norpethidine --- p.131 / Chapter Chapter 7 - --- "A Comparative Study of Plasma Pethidine and Norpethidine in Caucasian, Chinese and Nepalese Patients after Intramus- cular Post-operative Pethidine" --- p.153 / Chapter Chapter 8 - --- Future Prospects of the Work --- p.168 / References --- p.171 / Appendices

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 9 uppsatser.

An alternative complementary approach was used to verify the antinociceptive effect of 4 CMMs aqueous extracts in a Drosophila adult model. Drosophila adults were subjected to CMM treatments and then placed on an in-house-designed heating device for noxious heat stimulation. Their behavioral outputs were quantified and expressed as heat avoidance index (AI) for revealing the degree of antinociceptive effect of CMMs. By comparing the AI value of non-CMM treated control group with CMM-treated groups at temperature challenge 32°C, it was found that an AI value of 0.2 was obtained for non-CMM-treated control group whereas CMMs-treated groups showed AI values ranged from 0.33 to 0.4. The increase of AI value in those CMM-treated groups means that Drosophila adults became more susceptible to noxious heat stimulation. This indicates that those identified CMMs by the larvae model possess strong and versatile antinoceiceptive activities in Drosophila adults. / In addition, reverse transcription PCR (RT PCR) analysis was performed to study the effects of CMMs on the mRNA expression of three nociceptive-related genes painless, nompC and CG4536. These three genes all belong to the Transient Receptor Potential (TRP) families and have been shown to be involved in heat response. The results indicate that the gene expression level for nompC was significantly down-regulated with fold changes ranging from 0.2 to 0.7 upon 2 hrs treatment of three aqueous CMM extracts Citrus aurantium, Angelica dahurica and Vitex trifolia. However, there is no significant difference in gene expression level for painless and CG4536. / In this study, it has been demonstrated that Drosophila are feasible to use for screening CMMs with antinociceptive activity. While the data of the relative gene expression level for those target genes observed in this study may also serve as biomarkers for providing more evidence to investigate drugs have antinociceptive effects. In the future, such information paves the way for further development in the study of antinociceptive drugs. / Nociception is the reception of signals in the central nervous system (CNS) triggered by specialized sensory receptors which received stimuli such as electrical, thermal, mechanical, or chemical and response to escape from danger. Similar to humans, the fruitfly Drosophila display evolutionarily conserved nociceptive response that makes it suitable for in vivo nociceptive study. In this study, Drosophila larvae were used as initial screening model to investigate the antinociceptive effect that was caused by 61 randomly selected Chinese Medicinal Materials (CMMs). Upon noxious heat stimulation, 73% of larvae in the control group produced a stereotypical rolling behavior within 1 s. Among those tested CMMs, the results indicated that 4 aqueous CMMs extracts from Citrus aurantium L. (family: Rutaceae), Angelica dahurica (Fish. ex Hoffm.) Benth. et Hook (family: Umbelliferae), Vitex trifolia L. var. simplicifolia Cham. (family: Verbenaceae) and Panax notoginseng (Burk.) F. H. Chen (family: Araliaceae) were found to have strong antinociceptive effect on Drosophila larvae since less than 40% of the larvae have produced stereotypical rolling behavior within 1 s upon noxious heat stimulation. / "September 2007." / Advisers: Ming Liang Song; Ho Yin Edwin Chan. / Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4768. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 134-139). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

In the last decade, prescription of anticonvulsants for treatment of low back pain (LBP) increased 4-fold. Among them, topiramate has frequent side effects and a mechanism of action that is not fully understood. The authors describe a 65-year-old woman with dependence on topiramate prescribed for chronic LBP and discuss how she was successfully weaned off topiramate using duloxetine. A significant agonistic effect by topiramate on α-2 adrenergic receptors in the brain likely accounts for the symptoms of withdrawal that were seen. We attribute the resolution of her topiramate withdrawal symptoms to reduced norepinephrine (NE) release, a known effect of duloxetine administration.