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      Neurobiology of Acupuncture: Toward CAM

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          Abstract

          It has long been accepted that acupuncture, puncturing and scraping needles at certain points on the body, can have analgesic and anesthetic effects, as well as therapeutic effects in the treatment of various diseases. This therapy, including acupuncture anesthesia, has drawn the attention of many investigators and become a research subject of international interest around the world. Numerous studies have demonstrated that the nervous system, neurotransmitters, endogenous substances and Jingluo (meridians) may respond to needling stimulation and electrical acupuncture. An abundance of information has now accumulated concerning the neurobiological mechanisms of acupuncture, in relation to both neural pathways and neurotransmitters/hormonal factors that mediate autonomic regulation, pain relief and other therapeutics. Early studies demonstrated that the analgesic effects of electroacupuncture (EA) are mediated by opioid peptides in the periaqueductal gray. Recent evidence shows that nitric oxide plays an important role in mediating the cardiovascular responses to EA stimulation through the gracile nucleus-thalamic pathway. Other substances, including serotonin, catecholamines, inorganic chemicals and amino acids such as glutamate and α-aminobutyric acid (GABA), are proposed to mediate certain cardiovascular and analgesic effects of acupuncture, but at present their role is poorly understood. The increased interest in acupuncture health care has led to an ever-growing number of investigators pursuing research in the processes of the sense of needling touch, transduction of needling stimulation signals, stimulation parameters and placebos. In this Review, the evidence and understanding of the neurobiological processes of acupuncture research have been summarized with an emphasis on recent developments of nitric oxide mediating acupuncture signals through the dorsal medulla-thalamic pathways.

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          Introducing a placebo needle into acupuncture research.

          A problem acupuncture research has to face is the concept of a control group. If, in control groups, non-acupoint needling is done, physiological acupuncture effects are implied. Therefore the effects shown in this group are often close to those shown in the acupuncture group. In other trials, control groups have received obviously different treatments, such as transcutaneous electrical nervous stimulation or TENS-laser treatment; it is not clear if the effects of acupuncture are due only to the psychological effects of the treatment. We developed a placebo acupuncture needle, with which it should be possible to simulate an acupuncture procedure without penetrating the skin. In a cross-over experiment with 60 volunteers we tested whether needling with the placebo needle feels any different from real acupuncture. Of 60 volunteers, 54 felt a penetration with acupuncture (mean visual analogue scale [VAS] 13.4; SD 10.58) and 47 felt it with placebo (VAS 8.86; SD 10.55), 34 felt a dull pain sensation (DEQI) with acupuncture and 13 with placebo. None of the volunteers suspected that the needle may not have penetrated the skin. The placebo needle is sufficiently credible to be used in investigations of the effects of acupuncture.
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            Placebo controls for acupuncture studies.

            Many studies of acupuncture treatment are seriously flawed by methodological problems. Poor design, inadequate measures and statistical analysis, lack of follow-up data and sub-standard treatment are all too common. However, the major problem, which many investigators consider to be still unresolved, is the definition of an appropriate placebo control. The use of inappropriate placebo controls has bedeviled acupuncture research and led to serious misinterpretation of the results of clinical trials. While a number of different solutions have been proposed there is, as yet, no agreed way of assessing the adequacy of control conditions or of deciding which placebo to use in a particular trial. We propose that assessing the credibility of treatments and control conditions may provide a way forward to a more rigorous, consensus approach.
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              Blockade of opioid receptors in rostral ventral medulla prevents antihyperalgesia produced by transcutaneous electrical nerve stimulation (TENS).

              Although transcutaneous electrical nerve stimulation (TENS) is used extensively in inflammatory joint conditions such as arthritis, the underlying mechanisms are unclear. This study aims to demonstrate an opiate-mediated activation of descending inhibitory pathways from the rostral ventral medulla (RVM) in the antihyperalgesia produced by low- (4 Hz) or high-frequency (100 Hz) TENS. Paw withdrawal latency to radiant heat, as an index of secondary hyperalgesia, was recorded before and after knee joint inflammation (induced by intra-articular injection of 3% kaolin and carrageenan) and after TENS/no TENS coadministered with naloxone (20 microg/1 microl), naltrindole (5 microg/1 microl), or vehicle (1 microl) microinjected into the RVM. The selectivity of naloxone and naltrindole doses was tested against the mu-opioid receptor agonist [D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAMGO) (20 ng, 1 microl) and the delta2-opioid receptor agonist deltorphin (5 microg, 1 microl) in the RVM. Naloxone microinjection into the RVM blocks the antihyperalgesia produced by low frequency (p 0.05). In contrast, naltrindole injection into the RVM blocks the antihyperalgesia produced by high-frequency (p 0.05) TENS. The analgesia produced by DAMGO and deltorphin is selectively blocked by naloxone (p < 0.05) and naltrindole (p < 0.05), respectively. Thus, the dose of naloxone and naltrindole used in the current study blocks mu- and delta-opioid receptors, respectively. Hence, low-frequency and high-frequency TENS produces antihyperalgesia by activation of mu- and delta-opioid receptors, respectively, in the RVM.
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                Author and article information

                Journal
                Evid Based Complement Alternat Med
                Evidence-based Complementary and Alternative Medicine
                Evidence-based Complementary and Alternative Medicine
                Oxford University Press
                1741-427X
                1741-4288
                June 2004
                : 1
                : 1
                : 41-47
                Affiliations
                Departments of Obstetrics and Gynecology, Harbor–UCLA Medical Center, David Geffen School of Medicine at University of California at Los Angeles Torrance, CA, USA
                Author notes
                For reprints and all correspondence: Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, David Geffen School of Medicine at University of California at Los Angeles, 1124 W. Carson Street, RB-1, Torrance, CA 90502, USA. E-mail: ma@ 123456humc.edu
                Article
                10.1093/ecam/neh017
                442119
                15257325
                bf9cfdc3-6939-479d-9e1f-815de777bbfc
                © Oxford University Press, 2004.
                History
                : 23 December 2003
                : 27 February 2004
                Categories
                Reviews

                Complementary & Alternative medicine
                nitric oxide,opiate,acupuncture,neurobiology,neurotransmitter,pain

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