There remains a high degree of scepticism about acupuncture since its theoretical basis has no clear reference in Western medical and scientific terms, making any associations between neurophysiology and specific acupuncture concepts difficult to determine. Using neuroimaging and engineering approaches to understand its physiological basis may engender greater acceptance of and improvement in the clinical application of acupuncture. Research into the efficacy of acupuncture has raised a number of difficult methodological issues, particularly in relation to the selection of appropriate controls. Separating specific effects from non-specific effects is complex because acupuncture is a physical, invasive, manual procedure involving time and ritual. Sham acupuncture results show only the difference between sham and real acupuncture not the real affect of acupuncture, and other controls may produce distinct subjective and objective effects. Point injection (the injection of a small amount of a substance at an acupoint), a recent innovation of traditional acupuncture, aims to enhance and prolong the stimulation effect in a standardised, reproducible manner. By providing precise, measurable acupoint stimulation applied incrementally in a specifically designed paradigm, an acupoint could act as its own control. This firstly requires injection to be validated against traditional needling. Aims 1. To develop an instrument for reproducible saline delivery at an acupoint. 2. To cross-validate saline acupoint injection (PI) with traditional needle acupuncture (TA). 3. To demonstrate central nervous system (CNS) effects of acupuncture both in health and chronic pain. Hypothesis The primary hypothesis is that stimulation of specific acupoints with linearly incremental saline injection produces differential effects within the CNS observable with functional magnetic resonance imaging (fMRI) allowing investigation of acupuncture in health and chronic pain. Novelty As neuroimaging has not yet clearly defined the brain structures that may be modulated by acupuncture, this project is exploratory in nature. It is expected that acupuncture effects can be robustly imaged with fMRI in healthy subjects and those suffering chronic pain. The demonstrated effects will result from the acupuncture process of progressive point stimulation by tissue distension rather than needle insertion or biological noise. It is proposed to examine the putative modulation of pain by acupuncture within the extensively mapped neuromatrix of cortical and subcortical regions, including the somatic, insula, and limbic cortices, and thalamus. Detailed information regarding differences in brain response between acupuncture in normal and diseased states will expand understanding of acupuncture as a clinical tool. The dilemma of sham stimulation or arbitrary controls will be addressed by confirming PI as a valid, reproducible stimulation method. Methods and Results A series of empirical experiments was designed and conducted to determine the effects of stimulation of different acupoints. 1. Chapters 1 and 3 outline the current understanding of acupuncture in the Western milieu and a review of the neuroimaging literature respectively. 2. In Chapter 2, the report of PI tested against TA in healthy volunteers to determine equivalence of physiological effect demonstrates no statistically significant differences between the methodologies. 3. Chapter 4 reports the design and validation of a task specific microprocessor controlled syringe driver. 4. Four differing acupoints were tested during an fMRI experiment described in Chapter 5; different activation areas were demonstrated across the acupoints providing early support for the hypothesis that different acupoints may have different effects. A subset of brain areas recognised within the pain neuromatrix was delineated, congruent spatially and directionally with those reported in pharmacological analgesia studies. 5. As outlined in Chapter 6, heart rate variability can be measured rapidly in a stressful environment to provide meaningful data on the response of the autonomic nervous system to acupuncture stimulation. 6. The hypothesis of different acupoints having different effects was tested in subjects suffering chronic pain by contrasting an accepted and a neutral acupoint, the results being reported in Chapter 7. Conclusion Despite a long history of clinical usage, appropriate scientific studies have not yet addressed the basic effectiveness and efficacy of acupuncture. This thesis presents a series of empirical studies designed to address a number of the questions arising in the literature and provides converging evidence of the manner in which different acupoints modulate the CNS, specifically within the pain neuromatrix.

Title page, table of contents and summary only. The complete thesis in print form is available from the University of Adelaide Library. / HIV-1 infection of astrocytes is involved in HIV-1 induced neurological diseases and is a possible source of viral persistence. In situ studies of post mortem brain tissue indicate that HIV-1 infection of astrocytes does occur, but is restricted. Previous in vitro studies have revealed intrinsic intracellular blocks to HIV-1 transcription and translation in astrocytes. The early viral replication steps of entry, reverse transcription and integration have not been previously characterised in detail in astrocytes, and are the focus of this study. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1274468 / Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2007

There remains a high degree of scepticism about acupuncture since its theoretical basis has no clear reference in Western medical and scientific terms, making any associations between neurophysiology and specific acupuncture concepts difficult to determine. Using neuroimaging and engineering approaches to understand its physiological basis may engender greater acceptance of and improvement in the clinical application of acupuncture. Research into the efficacy of acupuncture has raised a number of difficult methodological issues, particularly in relation to the selection of appropriate controls. Separating specific effects from non-specific effects is complex because acupuncture is a physical, invasive, manual procedure involving time and ritual. Sham acupuncture results show only the difference between sham and real acupuncture not the real affect of acupuncture, and other controls may produce distinct subjective and objective effects. Point injection (the injection of a small amount of a substance at an acupoint), a recent innovation of traditional acupuncture, aims to enhance and prolong the stimulation effect in a standardised, reproducible manner. By providing precise, measurable acupoint stimulation applied incrementally in a specifically designed paradigm, an acupoint could act as its own control. This firstly requires injection to be validated against traditional needling. Aims 1. To develop an instrument for reproducible saline delivery at an acupoint. 2. To cross-validate saline acupoint injection (PI) with traditional needle acupuncture (TA). 3. To demonstrate central nervous system (CNS) effects of acupuncture both in health and chronic pain. Hypothesis The primary hypothesis is that stimulation of specific acupoints with linearly incremental saline injection produces differential effects within the CNS observable with functional magnetic resonance imaging (fMRI) allowing investigation of acupuncture in health and chronic pain. Novelty As neuroimaging has not yet clearly defined the brain structures that may be modulated by acupuncture, this project is exploratory in nature. It is expected that acupuncture effects can be robustly imaged with fMRI in healthy subjects and those suffering chronic pain. The demonstrated effects will result from the acupuncture process of progressive point stimulation by tissue distension rather than needle insertion or biological noise. It is proposed to examine the putative modulation of pain by acupuncture within the extensively mapped neuromatrix of cortical and subcortical regions, including the somatic, insula, and limbic cortices, and thalamus. Detailed information regarding differences in brain response between acupuncture in normal and diseased states will expand understanding of acupuncture as a clinical tool. The dilemma of sham stimulation or arbitrary controls will be addressed by confirming PI as a valid, reproducible stimulation method. Methods and Results A series of empirical experiments was designed and conducted to determine the effects of stimulation of different acupoints. 1. Chapters 1 and 3 outline the current understanding of acupuncture in the Western milieu and a review of the neuroimaging literature respectively. 2. In Chapter 2, the report of PI tested against TA in healthy volunteers to determine equivalence of physiological effect demonstrates no statistically significant differences between the methodologies. 3. Chapter 4 reports the design and validation of a task specific microprocessor controlled syringe driver. 4. Four differing acupoints were tested during an fMRI experiment described in Chapter 5; different activation areas were demonstrated across the acupoints providing early support for the hypothesis that different acupoints may have different effects. A subset of brain areas recognised within the pain neuromatrix was delineated, congruent spatially and directionally with those reported in pharmacological analgesia studies. 5. As outlined in Chapter 6, heart rate variability can be measured rapidly in a stressful environment to provide meaningful data on the response of the autonomic nervous system to acupuncture stimulation. 6. The hypothesis of different acupoints having different effects was tested in subjects suffering chronic pain by contrasting an accepted and a neutral acupoint, the results being reported in Chapter 7. Conclusion Despite a long history of clinical usage, appropriate scientific studies have not yet addressed the basic effectiveness and efficacy of acupuncture. This thesis presents a series of empirical studies designed to address a number of the questions arising in the literature and provides converging evidence of the manner in which different acupoints modulate the CNS, specifically within the pain neuromatrix.

Dissertation (Ph.D.).--University of Texas Graduate School of Biomedical Sciences at San Antonio, 2006. / Vita. Includes bibliographical references.

Thesis (Ph.D.)--Tufts University, 2003. / Adviser: Barry A. Trimmer. Submitted to the Dept. of Biology. Includes bibliographical references (leaves 147-164). Access restricted to members of the Tufts University community. Also available via the World Wide Web;

Diss. (sammanfattning) Stockholm : Karolinska institutet 2005. / I publ. felaktigt ISBN: 91-7140-442-4. Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Univ., 2003. / Härtill 5 uppsatser.

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

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.