[Challenges and choices: translational acupuncture research spectrum-a proposal].

For more than half a century，the modern bioresearch in acupuncture has made remarkable advancements, proving scientific basis underlying the traditional, intuitive treatment, as well as leading to some new discoveries with the potential to enhance the effectiveness of acupuncture as we know it. Meanwhile, the clinical researches have started to shift its paradigm from traditional individual observation to modern evidence-based medicine. However, there is little interaction between basic and clinic researches, which are like two separate worlds, not benefiting each other. Also the education and training of acupuncture are still traditional style, little combining with modern studies. To bridging the large gap, we need translational science involving in. In this article, with a critical reviews of the limitations of the traditional methods of acupuncture, the challenges faced by clinic practices and placebo-control studies, and the advantages and disadvantages of basic research, we propose a methodological paradigm of the translational research, Translational Acupuncture Research Spectrum, that meets the current situation of acupuncture researches, hoping to give insights into this field and to promote modern acupuncture to move towards a new stage.

[The significance of "A neuroanatomical basis for electroacupuncture to drive the vagal-adrenal axis" published in Nature for acupuncture research].

October 2021, Nature published an original research article entitled A neuroanatomical basis for electroacupuncture to drive the vagal-adrenal axis, which draws great attention and arouses extensive discussion in the acupuncture field. Based on previous findings, this study demonstrates that the abundant innervation of PROKR2-Cre neurons in deep fascia tissues mediates the anti-inflammatory effect induced by low-intensity electroacupuncture stimulation at "Zusanli"（ST36） or "Shousanli"(LI10) via the "vagal-adrenal axis". This study is one of milestones in the field of acupuncture basic research and represents a great achievement generated by multi-discipline integration of acupuncture and neuro-immunology. It reveals partial contributing factors involved in acupuncture's effect and the relative specificity of the neuroanatomical basis of acupoints in the context of immune modulation. This study is both very informative and instructive for the innovation and clinical translation of future acupuncture research. Acupuncture researchers are recommended to attach great importance to this study in terms of its research strategy,methods and findings.

[Discussion on Acupuncture as adjunctive therapy for chronic stable angina: a randomized clinical trial published in JAMA Internal Medicine].

Professor LIANG Fan-rong's team from Chengdu University of TCM published Acupuncture as adjunctive therapy for chronic stable angina: a randomized clinical trial in JAMA Internal Medicine on July 29, 2019, which demonstrates that acupuncture as an adjunctive therapy is safety and effective for mild and moderate chronic stable angina. Sixteen experts at home and abroad conducted serious discussions on the research design, evaluation methods, principles and mechanisms, clinical significance and enlightenment of future acupuncture research, and provided practical suggestions for acupuncture and moxibustion to go global and gain international recognition.

Acupuncture and Related Techniques for Pain Relief and Treatment of Heroin Addiction: Mechanisms and Clinical Application.

A neurochemical hypothesis of acupuncture analgesia suggests that the pain relief effect of acupuncture is primarily due to activation of a central endorphin system. It has been shown that the primary afferent sensory fibers, a mesolymbic neural circuit, and a descending inhibitory pathway are critical in acupuncture analgesia. The therapeutic effects of electroacupuncture (EA) and related techniques, such as transcutaneous electroacupoint stimulation (TEAS), are frequency-dependent: different frequencies of EA activate different brain regions and release different neuropeptides. EA and TEAS have been used successfully to treat heroin addiction. Activation of endorphin gene expression and release by TEAS can explain the dramatic attenuation of withdrawal syndrome and prolongation of retention time during and after detoxification treatment in patients who are addicted to heroin. However, repeated EA at high intensity should be avoided because it can induce a gradual loss of the analgesic effect. Opioid-receptor desensitization occurs and is manifested as decreased ligand-binding affinity and second-messenger detachment. Repeated large doses of morphine induce morphine tolerance. Cross-tolerance between morphine and EA suggests similar underlying mechanisms. Recent studies have demonstrated that excessive activation of cholecystokinin (CCK), an antiopioid peptide, appears to be responsible. CCK-receptor subtype B (CCKBR) and opioid µ-receptor are co-expressed in the dorsal-horn neurons. Activation of CCKBR promotes formation of heteromerization of morphine-receptor and CCKBR. Interaction of the third transmembrane domain between the 2 receptors resulted in the reduced binding affinity of the opioid receptor.

Responses of Primary Afferent Fibers to Acupuncture-Like Peripheral Stimulation at Different Frequencies: Characterization by Single-Unit Recording in Rats.

The pain-relieving effect of acupuncture is known to involve primary afferent nerves (PANs) via their roles in signal transmission to the CNS. Using single-unit recording in rats, we characterized the generation and transmission of electrical signals in Aß and Aδ fibers induced by acupuncture-like stimuli. Acupuncture-like signals were elicited in PANs using three techniques: manual acupuncture (MAc), emulated acupuncture (EAc), and electro-acupuncture (EA)-like peripheral electrical stimulation (PES). The discharges evoked by MAc and EAc were mostly in a burst pattern with average intra-burst and inter-burst firing rates of 90 Hz and 2 Hz, respectively. The frequency of discharges in PANs was correlated with the frequency of PES. The highest discharge frequency was 246 Hz in Aß fibers and 180 Hz in Aδ fibers. Therefore, EA in a dense-disperse mode (at alternating frequency between 2 Hz and 15 Hz or between 2 Hz and 100 Hz) best mimics MAc. Frequencies of EA output >250 Hz appear to be obsolete for pain relief.

[A Preliminary Study on Effect of Transcutaneous Electrical Acupoint Stimulation for Children with Autism].

OBJECTIVE: To investigate the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) in treating children with autism spectrum disorders. METHODS: Forty-one autistic children receiving rehabilitation training were randomized into TEAS (n=21) and control (n=20) groups. The control group only received rehabilitation training. The TEAS group received both rehabilitation training and TEAS treatment[2 Hz/15 Hz alternating frequencies through two pairs of skin electrodes placed at Hegu (LI 4)-Neiguan (PC 6) on unilateral side, and Zusanli (ST 36)-Sanyinjiao (SP 6) on the contralateral side]. The treatment was given 30 min per day for 12 weeks. The outcome assessment was quantified with a series of rating scales including Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS) and Parent Symptom Questionnaire (PSQ). RESULTS: (1) The TEAS group showed more significant improvement than the control group in ABC (P<0.01). 38.1% effective rate (8/21) was observed in the TEAS group compared to 5.0% (1/20) in the control group (P<0.05). The CARS scores of both groups were reduced (P<0.0001) after treatment. The TEAS group showed significantly lower score compared to the control group (P<0.0001). (2)There was a distinctly reduced PSQ score in both TEAS and control groups (P<0.001) after treatment.(3)TEAS intervention showed better effect in children under 6 years old with moderate or severe autistic symptoms. CONCLUSIONS: TEAS intervention can significantly improve the autistic symptoms.

Use of electroacupuncture and transcutaneous electrical acupoint stimulation in reproductive medicine: a group consensus.

With the rapid development of assisted reproductive technology, various reproductive disorders have been effectively addressed. Acupuncture-like therapies, including electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS), become more popular world-wide. Increasing evidence has demonstrated that EA and TEAS are effective in treating gynecological disorders, especially infertility. This present paper describes how to select acupoints for the treatment of infertility from the view of theories of traditional Chinese medicine and how to determine critical parameters of electric pulses of EA/TEAS based on results from animal and clinical studies. It summarizes the principles of clinical application of EA/TEAS in treating various kinds of reproductive disorders, such as polycystic ovary syndrome (PCOS), pain induced by oocyte retrieval, diminished ovarian reserve, embryo transfer, and oligospermia/ asthenospermia. The possible underlying mechanisms mediating the therapeutic effects of EA/TEAS in reproductive medicine are also examined.

Effects of chronic restraint stress on social behaviors and the number of hypothalamic oxytocin neurons in male rats.

Oxytocin (OXT) and vasopressin (AVP) are considered to be related to mammalian social behavior and the regulation of stress responses. The present study investigated the effects of chronic homotypic restraint stress (CHRS) on social behaviors and anxiety, as well as its repercussions on OXT- and AVP-positive neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) nuclei in rat. Male Sprague-Dawley rats receiving CHRS were exposed to repeated restraint stress of 30min per day for 10days. Changes in social approach behaviors were evaluated with the three-chambered social approach task. Changes in anxiety-like behaviors were evaluated in the light-dark box test. The number of neurons expressing oxytocin and/or vasopressin in PVN and SON were examined by immunohistochemistry techniques. The results demonstrated that social approach was increased and anxiety was decreased following 10-day exposure to CHRS. Furthermore, the number of OXT-immunoreactive cells in PVN was increased significantly, whereas no change in SON was seen. The number of AVP immunoreactive cells either in PVN or SON was unaffected. The results of this study suggest that certain types of stress could be effective in the treatment of social dysfunction in persons with mental disorders such as autism, social anxiety disorder. The therapeutic effects may be mediated by changes in the function of OXT neurons in PVN.

Electro-acupuncture improves the social interaction behavior of rats.

Oxytocin (OXT) and arginine-vasopressin (AVP) are two closely related neuropeptides and implicated in the regulation of mammalian social behaviors. A prior clinical study in our laboratory suggested that electro-acupuncture (EA) alleviated social impairment in autistic children accompanied by changes of peripheral levels of OXT and AVP. However, it remains unclear whether EA stimulation had an impact on central OXT and AVP levels. In the present study, rats were subjected to a single session of EA (sEA) or repeated sessions of EA (rEA). Following the stimulation, mRNA levels and peptide levels of OXT/AVP systems were determined. The results showed that sEA led to region-specific up-regulation of OXT and AVP mRNA levels in the hypothalamus where the peptides were produced, without affecting the content of OXT and AVP in the hypothalamus and peripheral blood. The rEA of 5 sessions in 9 days was given to the low socially interacting (LSI) rats. LSI rats that underwent rEA showed significant improvement of social behavior characterized by spending more time investigating the strange rats in the three-chamber sociability test. The improved sociability was accompanied by an up-regulation of mRNA and the peptide levels of OXT or AVP in SON of the hypothalamus as well as a significant increase of the serum level of AVP. It is concluded that activation of OXT/AVP systems may be associated with the pro-social effect caused by EA stimulation.

Transcutaneous electrical acupoint stimulation in children with autism and its impact on plasma levels of arginine-vasopressin and oxytocin: a prospective single-blinded controlled study.

Acupuncture increases brain levels of arginine-vasopressin (AVP) and oxytocin (OXT), which are known to be involved in the modulation of mammalian social behavior. Transcutaneous electrical acupoint stimulation (TEAS) is often used clinically to produce a similar stimulation to that of acupuncture on the acupoints. In the present study, TEAS was applied to children with autism to assess its therapeutic efficacy. Seventy-six autistic children receiving rehabilitation training were divided into 2 groups: a treatment group receiving TEAS 30min per day, 5 days per week for 12 weeks (n=37) and a control group without TEAS treatment (n=39). A series of rating scales was used in outcome assessment. Plasma levels of AVP and OXT were determined by enzyme immunoassay (EIA) before and after treatment. The TEAS group showed a significant improvement over the control in their emotional response, fear or anxiety, level/consistency of intellective relations and general impressions on the Childhood Autism Rating Scale (CARS) as well as improvements in the sensory and related factors in the Autism Behavior Checklist (ABC). In addition, the varieties of accepted food increased after TEAS treatment. It appears that TEAS was effective in autistic children who showed passive and aloof behavior, but not in those who were active but odd. The plasma level of AVP was significantly higher in the TEAS group than in the control group after the intervention. In addition, the change in the plasma AVP level paralleled the improvement of some of the behavior factors in CARS, including adaptation to environmental change, listening response, perceptive response and fear or anxiety. It is concluded that TEAS is effective for the treatment of autistic children with a passive and aloof social interaction style. Changes in plasma levels of AVP and possibly OXT may be involved in mediating the therapeutic effect of TEAS.