PREFACE Acupuncture is a fundamental part of traditional Chinese medicine. Over its 3000 years of development, a wealth of experience has been accumulated in the practice of acupuncture, attesting to a wide range of diseases and conditions that can be effectively treated by this approach. Modern acupuncture can be defined as insertion of fine thin needles into the specific points on the body with mechanical, electrical, or other physical manipulations, which stimulate nerve receptors both directly or indirectly mechanical coupling with connective tissue surrounding the needles. In general, the acupuncture stimulation, through the local reflex and central nervous system, induces endocrine, neuroendocrine, autonomic, and systemic behavioral responses. This suggests that acupuncture therapy may beneficially affect a whole body even if it, using a few fine needles, stimulates only limited sites of the body. Within past three decades, there has been a rapid progress in acupuncture research including neuroscience due to the development of modern technology and ever increasing demand for a more efficient and cost-effective health-care system. We believe that there is a need to compile a book to summarize the recent developments in acupuncture research and, in particular, the neurobiology of acupuncture, and that this will promote understanding and enhance acupuncture research in the future. In this volume, a talented group of scientists and/or clinicians review the major breakthrough and capture the status of the fields, from clinic issues to basic science and feedback to the clinic, from body systems to tissues, to cells and molecules; from past to present days and future challenges. We have tried to cover as many topics as possible although it is ultimately impossible to get every topic in one volume regarding vast amount of information in the literature. Recently, efficacy in acupuncture has been intensively debated due to the failure of some large scales of clinical trials in chronic pain. This is a critical and urgent issue for future acupuncture research. “Acupuncture point specificity” by J-.J. Xing reviews recent development in basic science and clinical studies on the role of acupoint specificity. Evidence cumulated from brain image and biological studies showed that acupoint specificity does exist although acupuncture needling, acupoint location, and more importantly acupoint specificity-related issues, such as sham acupuncture, and placebo phenomena should be seriously considered before analyzing the efficacy of acupuncture. xv
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Bench science provides fundamental insight and mechanisms of many subjects including acupuncture. “Effects of acupuncture needling with specific sensation on cerebral hemodynamics and autonomic nervous activity in humans” by K. Takamoto focuses on the cerebral hemodynamic responses and autonomic nervous activity changes induced by acupuncture stimulation with or without de-qi sensation. Interestingly, the authors argued that acupuncture-induced specific de-qi sensation is more important than specific acupoint stimulation for inducing cerebral hemodynamic responses and changes in autonomic nervous activity. Then, “Acupuncture stimulation induces neurogenesis in adult brain” by M-.H. Nam reviews recent studies on the effect of stimulation at ST36 and GV20 for adult neurogenesis. They showed that acupuncture-induced upregulation of neurotrophic factors such GDNF, BDNF, and activation of primo vascular system in the brain all contribute to the enhanced neurogenesis in the brain. “Acupuncture stimulation and neuroendocrine regulation” by J-.S. Yu provides evidence from literature review that somatic stimulation by acupuncture has specific pathways and central sites for its action in the spinal cord and different regions of brain, and needling-specific acupoint triggers the release of neurotransmitters, neurohormones, and opioids which have wide range of effects on different body systems. “Acupuncture and neurotrophin modulation” by M. Soligo reviews evidence from animal models and human subjects that acupuncture stimulation increases neurotrophin expression/ action not only in peripheral system and target organs but also in spinal cord and brain although further studies are needed to investigate the underlying mechanisms of acupuncture on neurotrophin modulation. “Acupuncture regulation of blood pressure: Two decades of research” by J.C. Longhurst reviews the development in acupuncture regulation of blood pressure in their laboratory. Their studies showed that acupoint stimulation activated somatic input to different brain regions, including ventral hypothalamic arcuate nucleus and midbrain vlPAG, leading to prolonged release of opioids and GABA and nociceptin, in addition to other neurotransmitter, acting postsynaptically to directly or indirectly modulate autonomic outflow, guiding to a long-lasting reduction of blood pressure. “Effect and mechanism of acupuncture on gastrointestinal diseases” by T. Takahashi focuses on effect of acupuncture stimulation on gastrointestinal system and finds that acupuncture stimulation of somato-sensory neurons activates various nuclei at the CNS, leading to modulating the imbalance between sympathetic and parasympathetic activity, releasing opioids and
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OXT. These mechanisms underlie acupuncture treatment of GI disorders such as dysmotility, visceral hypersensitivity, and visceral pain. “Acupuncture therapy for psychiatric illness” by K. Pilkington summarizes acupuncture-induced central mediators such as serotonin, norepinephrine, dopamine, and glutamate and their roles in specific psychological disorders such as anxiety disorders, depression, bipolar disorder, and schizophrenia. “Acupuncture for the treatment of insomnia” by K. Zhao provides a comprehensive understanding of the efficacy of acupuncture therapy for insomnia and a list of acupoints used in clinical trials between 2007 and 2013; and very useful suggestions that integrated approaches to explore the efficacy of acupuncture are applicable not only to insomnia but also to other conditions. “Acupuncture for the treatment of drug addiction” by C-.L. Cui retrospects three important steps in the acupuncture treatment of substance abuse, including pioneer work by Dr. Wen in Hong Kong, in 1972, that acupuncture at four body points and two ear points combined with electrical stimulation can relieve opioid withdrawal signs in the addicts. Then, Dr. Smith, in New York, finalized a protocol (1985), using only ear points without electrical stimulation for the treatment of cocaine dependence. Recently, Dr. Han from Beijing characterized a protocol (2005), using electrical stimulation of identified frequencies on body points to ameliorate heroin withdrawal signs and reduce relapse of heroin use. Recently, the use of acupuncture in neurological disorders has been expanded from stroke to neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. “Acupuncture therapy for stroke patients” by X. Li reviews literature of stroke and provides evidence from both animal models and clinic studies that acupuncture therapy is not only effective in improving stroke function recovery but can also be used as a preventive strategy which could lead to ischemic tolerance when combined with electrotherapy. “Current development of acupuncture research in Parkinson’s disease” by B-.Y. Zeng focuses on the underlying mechanisms of acupuncture on Parkinson’s models. Evidence has showed that acupuncture has neuroprotective potential by increasing release of neurotrophic factors in basal ganglia area, it can slow down cell death by exerting antioxidant and antiinflammatory effects, and further, it modulated neuronal activity in the basal ganglia output structure. “Effect and Mechanism of Acupuncture on Alzheimer’s Disease” by B.Y. Zeng showed that acupuncture stimulation at Alzheimer’s models enhanced cholinergic neurotransmission, trophic factor releasing, improve synaptic plasticity, and decrease the levels of Ab
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proteins in the hippocampus and relevant brain regions. fMRI image of patients with AD demonstrated that acupuncture increased in the activity in the temporal lobe and prefrontal lobe, paralleling to the improving memory and cognitive function. “History of acupuncture research” by Y. Zhuang not only retrospects the past acupuncture research but also reviews the current achievements and discusses the challenges faced by acupuncture researchers in future, in particular how to improve efficacy of acupuncture and minimize the impact of sham acupuncture and placebo phenomena, how to improve methodology in design and evaluation of clinical studies, and furthermore, how to reconcile the individualized treatment in TCM with blinding and standardized controlling clinical trials. It seems that the need for unified standards and evaluation index particularly in acupuncture clinical studies may be one of the rationales. Finally, we would like to thank the excellent group of scientists who contributed a brilliant set of chapters to make up this volume, and dedicated editorial staff to accomplish this book. BAI-YUN ZENG KAICUN ZHAO FAN-RONG LIANG
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Bench science provides fundamental insight and mechanisms of many subjects including acupuncture. “Effects of acupuncture needling with specific sensation on cerebral hemodynamics and autonomic nervous activity in humans” by K. Takamoto focuses on the cerebral hemodynamic responses and autonomic nervous activity changes induced by acupuncture stimulation with or without de-qi sensation. Interestingly, the authors argued that acupuncture-induced specific de-qi sensation is more important than specific acupoint stimulation for inducing cerebral hemodynamic responses and changes in autonomic nervous activity. Then, “Acupuncture stimulation induces neurogenesis in adult brain” by M-.H. Nam reviews recent studies on the effect of stimulation at ST36 and GV20 for adult neurogenesis. They showed that acupuncture-induced upregulation of neurotrophic factors such GDNF, BDNF, and activation of primo vascular system in the brain all contribute to the enhanced neurogenesis in the brain. “Acupuncture stimulation and neuroendocrine regulation” by J-.S. Yu provides evidence from literature review that somatic stimulation by acupuncture has specific pathways and central sites for its action in the spinal cord and different regions of brain, and needling-specific acupoint triggers the release of neurotransmitters, neurohormones, and opioids which have wide range of effects on different body systems. “Acupuncture and neurotrophin modulation” by M. Soligo reviews evidence from animal models and human subjects that acupuncture stimulation increases neurotrophin expression/ action not only in peripheral system and target organs but also in spinal cord and brain although further studies are needed to investigate the underlying mechanisms of acupuncture on neurotrophin modulation. “Acupuncture regulation of blood pressure: Two decades of research” by J.C. Longhurst reviews the development in acupuncture regulation of blood pressure in their laboratory. Their studies showed that acupoint stimulation activated somatic input to different brain regions, including ventral hypothalamic arcuate nucleus and midbrain vlPAG, leading to prolonged release of opioids and GABA and nociceptin, in addition to other neurotransmitter, acting postsynaptically to directly or indirectly modulate autonomic outflow, guiding to a long-lasting reduction of blood pressure. “Effect and mechanism of acupuncture on gastrointestinal diseases” by T. Takahashi focuses on effect of acupuncture stimulation on gastrointestinal system and finds that acupuncture stimulation of somato-sensory neurons activates various nuclei at the CNS, leading to modulating the imbalance between sympathetic and parasympathetic activity, releasing opioids and
Preface
xvii
OXT. These mechanisms underlie acupuncture treatment of GI disorders such as dysmotility, visceral hypersensitivity, and visceral pain. “Acupuncture therapy for psychiatric illness” by K. Pilkington summarizes acupuncture-induced central mediators such as serotonin, norepinephrine, dopamine, and glutamate and their roles in specific psychological disorders such as anxiety disorders, depression, bipolar disorder, and schizophrenia. “Acupuncture for the treatment of insomnia” by K. Zhao provides a comprehensive understanding of the efficacy of acupuncture therapy for insomnia and a list of acupoints used in clinical trials between 2007 and 2013; and very useful suggestions that integrated approaches to explore the efficacy of acupuncture are applicable not only to insomnia but also to other conditions. “Acupuncture for the treatment of drug addiction” by C-.L. Cui retrospects three important steps in the acupuncture treatment of substance abuse, including pioneer work by Dr. Wen in Hong Kong, in 1972, that acupuncture at four body points and two ear points combined with electrical stimulation can relieve opioid withdrawal signs in the addicts. Then, Dr. Smith, in New York, finalized a protocol (1985), using only ear points without electrical stimulation for the treatment of cocaine dependence. Recently, Dr. Han from Beijing characterized a protocol (2005), using electrical stimulation of identified frequencies on body points to ameliorate heroin withdrawal signs and reduce relapse of heroin use. Recently, the use of acupuncture in neurological disorders has been expanded from stroke to neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. “Acupuncture therapy for stroke patients” by X. Li reviews literature of stroke and provides evidence from both animal models and clinic studies that acupuncture therapy is not only effective in improving stroke function recovery but can also be used as a preventive strategy which could lead to ischemic tolerance when combined with electrotherapy. “Current development of acupuncture research in Parkinson’s disease” by B-.Y. Zeng focuses on the underlying mechanisms of acupuncture on Parkinson’s models. Evidence has showed that acupuncture has neuroprotective potential by increasing release of neurotrophic factors in basal ganglia area, it can slow down cell death by exerting antioxidant and antiinflammatory effects, and further, it modulated neuronal activity in the basal ganglia output structure. “Effect and Mechanism of Acupuncture on Alzheimer’s Disease” by B.Y. Zeng showed that acupuncture stimulation at Alzheimer’s models enhanced cholinergic neurotransmission, trophic factor releasing, improve synaptic plasticity, and decrease the levels of Ab
xviii
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proteins in the hippocampus and relevant brain regions. fMRI image of patients with AD demonstrated that acupuncture increased in the activity in the temporal lobe and prefrontal lobe, paralleling to the improving memory and cognitive function. “History of acupuncture research” by Y. Zhuang not only retrospects the past acupuncture research but also reviews the current achievements and discusses the challenges faced by acupuncture researchers in future, in particular how to improve efficacy of acupuncture and minimize the impact of sham acupuncture and placebo phenomena, how to improve methodology in design and evaluation of clinical studies, and furthermore, how to reconcile the individualized treatment in TCM with blinding and standardized controlling clinical trials. It seems that the need for unified standards and evaluation index particularly in acupuncture clinical studies may be one of the rationales. Finally, we would like to thank the excellent group of scientists who contributed a brilliant set of chapters to make up this volume, and dedicated editorial staff to accomplish this book. BAI-YUN ZENG KAICUN ZHAO FAN-RONG LIANG
