The modulation of brain functional connectivity with manual acupuncture in healthy subjects:An electroencephalograph case study

Manual acupuncture is widely used for pain relief and stress control.Previous studies on acupuncture have shown its modulatory effects on the functional connectivity associated with one or a few preselected brain regions.To investigate how manual acupuncture modulates the organization of functional networks at a whole-brain level,we acupuncture at ST36 of a right leg to obtain electroencephalograph（EEG） signals.By coherence estimation,we determine the synchronizations between all pairwise combinations of EEG channels in three acupuncture states.The resulting synchronization matrices are converted into functional networks by applying a threshold,and the clustering coefficients and path lengths are computed as a function of threshold.The results show that acupuncture can increase functional connections and synchronizations between different brain areas.For a wide range of thresholds,the clustering coefficient during acupuncture and postacupuncture period is higher than that during the pre-acupuncture control period,whereas the characteristic path length is shorter.We provide further support for the presence of ＂small-world＂ network characteristics in functional networks by using acupuncture.These preliminary results highlight the beneficial modulations of functional connectivity by manual acupuncture,which could contribute to the understanding of the effects of acupuncture on the entire brain,as well as the neurophysiological mechanisms underlying acupuncture.Moreover,the proposed method may be a useful approach to the further investigation of the complexity of patterns of interrelations between EEG channels.

Pretreatment of emulational manual acupuncture versus electroacupuncture against visceral traction pain in rats

BACKGROUND： Acupuncture and moxibustion against visceral noxious stimulation present different mechanisms in the peripheral and central nervous systems, involving release of neurotransmitter substance P, acetylcholine esterase, leucine-enkephalin, and c-Fos protein expression. However, there are few reports addressing changes in neurotransmitter expression following manual acupuncture and electroacupuncture against visceral traction pain.OBJECTIVE： To explore changes in neurotransmitter expression in the ileum and protein expression in the medullary visceral zone of visceral traction pain rats undergoing pretreatment of emulational manual acupuncture, and to investigate the differences between emulational manual acupuncture and electroacupuncture.DESIGN, TIME AND SETTING： The randomized, controlled study was performed at the Biomedical Engineering Laboratory, Shanghai University of Traditional Chinese Medicine, Shanghai, China from August 2008 to July 2009.MATERIALS： G6805 electroacupuncture apparatus （Shanghai Medical Electronic Machine Factory, China） and ZSF-I acupuncture manipulation simulation therapeutic system （Chinese Medical Engineering Room, Shanghai University of Traditional Chinese Medicine, Shanghai China） were used in the present study.METHODS： A total of 40 male Sprague Dawley rats were equally and randomly assigned to sham surgery, model, emulational manual acupuncture and electroacupuncture groups. In the emulational manual acupuncture and electroacupuncture groups, emulational manual acupuncture and electroacupuncture were applied at bilateral Zusanli （ST 36） acupoints for 30 minutes, and models of visceral traction pain were established immediately.MAIN OUTCOME MEASURES： Substance P expression, c-Fos and glial fibrillary acidic protein expression were measured using immunohistochemistry. Acetylcholine esterase activity was examined utilizing a colorimetric method. Leucine-enkephalin content was detected using a radioimmune assay. Degree of pain in rats was assessed by pain score.RESULTS： Pain score, substance P expression in the ileum, acetylcholine esterase activity, expression of c-Fos protein and glial fibrillary acidic protein in the medullary visceral zone were significantly decreased following pretreatment of emulational manual acupuncture and electroacupuncture in rats with visceral traction pain （P〈0.05）. Compared with the electroacupuncture group, the leucine-enkephalin content was significantly increased, and pain score was significantly diminished in the emulational manual acupuncture group （P〈0.05）.CONCLUSION： Emulational manual acupuncture pretreatment decreases acetylcholine esterase activity, increases leucine-enkephalin release, downregulates expression of c-Fos protein and glial fibrillary acidic protein and ultimately inhibits visceral traction pain by reducing substance P release. The effectiveness in inhibiting visceral traction pain is greater when using emulational manual acupuncture compared with electroacupuncture. This is because emulational manual acupuncture effectively increases leucine-enkephalin release.

Modulation of electroencephalograph activity by manual acupuncture stimulation in healthy subjects:An autoregressive spectral analysis

To investigate whether and how manual acupuncture（MA） modulates brain activities,we design an experiment where acupuncture at acupoint ST36 of the right leg is used to obtain electroencephalograph（EEG） signals in healthy subjects.We adopt the autoregressive（AR） Burg method to estimate the power spectrum of EEG signals and analyze the relative powers in delta（0 Hz-4 Hz）,theta（4 Hz-8 Hz）,alpha（8 Hz-13 Hz）,and beta（13 Hz-30 Hz） bands.Our results show that MA at ST36 can significantly increase the EEG slow wave relative power（delta band） and reduce the fast wave relative powers（alpha and beta bands）,while there are no statistical differences in theta band relative power between different acupuncture states.In order to quantify the ratio of slow to fast wave EEG activity,we compute the power ratio index.It is found that the MA can significantly increase the power ratio index,especially in frontal and central lobes.All the results highlight the modulation of brain activities with MA and may provide potential help for the clinical use of acupuncture.The proposed quantitative method of acupuncture signals may be further used to make MA more standardized.

MANUAL ACUPUNCTURE PRODUCES LONG TERM INHIBITION OF THE NOCICEPTIVE TRANSMISSION TO WIDE DYNAMIC RANGE NEURONS IN THE SPINAL CORD OF THE RAT

singe unit discharge recordings were made from 42 WDR neurons in spinal dorsal horn in the rat. These neurons could he driven by electrical stimull activiting innocuous and noxious afferent fibres in the ipsilateral plantar nerve. Traditional manual acupuncture delivered at the local acupoints Zusanli, Chengshan, Kunlun and Yongquan induced a strong inhibition or the C-fiber response. in 19 of 42 neurons obtained but did not after the A-fibre response of the neurons. The inhibition of the fibre response outlasted the period of acupuncture for more than 30 min. Neither Anor C-fibre responses in the remaining 23 neurous could be affected by manual acupuncture. These results suggest that the acupuncture stimulation specifically influences nociceptive nociceptive transmission,maybe through a presynaptic action,Furthermore, the fact that the inhibitory effect outlasts the stimulation by more than 30 min indicates that either a neuromodulatory ,presumably peptidergic action is at hand or that a temporary synaptic modification occurs in the spinal dorsal horn.

Initiation of Acupoint Molecular Mechanisms for Manual Acupuncture Analgesia—Nuclear FactorκB Signaling Pathway

Objective To identify the prominent molecular signaling in acupoints and explore their roles in initiating the analgesia effect of manual acupuncture(MA).Method A three-step study was conducted,the experiment 1 was a genome-wide analysis of the tissue at acupoint Zusanli(ST 36),including 12 Wistar rats which were divided into control,control+MA1,and control+MA7 groups.In the experiment 2,the paw withdrawal latency(PWL),immunohistochemistry and Western blot analysis of phospho-nuclear factor kappa B(NFκB)p65(p-p65),phospho-NFκB p50(p-p50)at ST 36 were performed on rats of saline,saline+MA,and complete Freund’s adjuvant(CFA)+MA groups(n=6).In experiment 3,24 rats were divided into saline+DMSO,CFA+DMSO,CFA+DMSO+MA,and CFA+BAY 11–7082+MA groups,the PWL and immunofluorescence assay of NFκB p65 at ST 36 was conducted.Result(1)The gene:inhibitor of NFκB(Nfkbia),interleukin-1β(Il1b),interleukin-6(Il6),chemokine c-x-c motif ligand 1(Cxcl1),monocyte chemoattractant protein-1(MCP-1/Ccl2)expressions in the control+MA7 group were significantly increased(P<0.05 or P<0.01),and the expression of NFκB p65(Rela),NFκB p50(Nfkb1)were increased in the control+MA7 group(P<0.05).(2)CFA+MA groups showed increased PWL from day 1 to 7(P<0.01 vs.CFA),and the Western blot results were consistent with immunohistochemistry,the expression of NFκB p-p65 and NFκB p-p50 were significantly increased in the MA-related groups compared with control and CFA groups(P<0.05).(3)Compared with the CFA+DMSO+MA group,the PWL of the CFA+BAY 11–7082+MA group decreased significantly and continued until day 5 and 7(P<0.05 and P<0.01,respectively),and the NFκB p65 expression of CFA+BAY 11–7082+MA was significantly reduced compared with CFA+DMSO+MA(P<0.01).Conclusion Local NFκB signaling cascade in acupoint caused by MA is an important step in initiating the analgesic effect,which would provide new evidence for the initiation of MA-effect and improve the understanding of the scientific basis of acupuncture analgesia.

Labor Pain Treated with Acupuncture or Acupressure

Opioid-dependent women have an 80% to 90% unintended pregnancy rate, almost double the overall unintended pregnancy rate: 40% globally and 51% in north America. The prescription drug abuse milieu increases the possibility opioid abusing laboring patients. In 2012, neonatal abstinence syndrome occurred in 5.8 per 1000 hospital births. Non-pharmacological labor pain management (NPLPM) is especially recommended for laboring patients with a history of substance abuse. Therefore, literature review was performed to elucidate the efficacy and safety of acupuncture, noninvasive electro-acupuncture (EA), and acupressure in labor pain management. Compared to standard intrapartum controls, bilateral EA at JiaJin or Sanyinjiao significantly reduced visual analog scale (VAS) pain scores 30-minutes post intervention (p < 0.01) and Stage 1 active phase labor length (p < 0.05). EA achieves shorter Stage 2 labor than patient-controlled epidural analgesia (p = 0.05);and 10-point lower VAS pain scores and reduced cesarean delivery rate than no-analgesia controls, p < 0.05. Current evidence indicates that EA should have a role in NPLPM, and that acupressure may have a role in NPLPM. Nevertheless, future RCTs could strengthen the argument for increased EA and acupressure use in NPLPM.

De-qi,Not Psychological Factors,Determines the Therapeutic Efficacy of Acupuncture Treatment for Primary Dysmenorrhea

Objective： To study the impact of De-qi （得气%, obtaining qi） and psychological factors on the efficacy of acupuncture treatment for primary dysmenorrhea, with an attempt to explore the relationship among De-qi, psychological factors, and clinical efficacy. Methods： The patients with primary dysmenorrhea were randomly assigned to a group of acupuncture with manual manipulation （manipulation group, n=67） and an acupuncture group without manipulation （non-manipulation group, n=64）. Pain intensity and pain duration were used as measures for evaluating the therapeutic efficacy of the acupuncture treatment. De-qi, the sensations a patient experienced during the acupuncture treatment, was scored on a 4-point scale by the subjects. In addition, the psychological factors, including belief in acupuncture, the level of nervousness, anxiety, and depression, were quantitatively assessed. The personality of the subject was assessed using the Eysenck personality questionnaire （EPQ） and 16 personality factor questionnaire （16PF）. Results： Complete data were obtained from 120 patients, 60 patients in each group. There were statistically significant differences in pain intensity （W=2410.0, P〈0.01 ） and pain duration （W=3181.0, P〈0.01） between the two groups. The number of De-qi acupoints （W=1150.5, P〈0.01） and the average intensity of De-qi （W=1141.0, P〈0.01） were significantly higher in the manipulation group as compared with their non-manipulation counterparts. The correlation coefficients between De-qi and therapeutic efficacy of acupuncture were greater than those between psychological factors and therapeutic efficacy. Conclusions： Compared with the psychological factors, De-qi contributed more to the pain-relieving effect of acupuncture in subjects with primary dysmenorrhea. Moreover, manual manipulation is a prerequisite for eliciting and enhancing the De-qi sensations, and De-qi is critical for achieving therapeutic effects.

Acupuncture Enhances Signalsat Sensitized Acupoints to Elevate Pressure Pain Thresholdin Knee Osteoarthritis Patients

Objective:To observe the pressure pain threshold(PPT),skin conductance(SC)and blood perfusion(BP)of the sensitized acupoints in patients with knee osteoarthritis(KOA),and explore the mechanism of acupuncture at the sensitized acupoints for treating diseases.Methods:Eleven healthy subjects and 11 unilateral KOA patients were recruited from July 2020 to March 2021 in this study.The PPT,SC and BP of control acupoints in healthy controls,and non-sensitized and sensitized acupoints in KOA patients were measured and compared between baseline and after manual acupuncture(MA)treatment.Results:Before MA treatment,lower PPT was observed at the sensitized acupoints comparedwith non-sensitized andcontrol acupoints(P<0.05).After MA treatment,PPT at the sensitized acupoints increased significantly in KOA patients(P<0.05).Before MA treatment,there was no statistical difference in SC and BP among control,non-sensitized and sensitized acupoints(P>0.05).Compared with the control and non-sensitized acupoints,there were significant increases of SC and BP in sensitized acupoints of KOA patients after MA treatment(P<0.05 or P<0.01).Conclusion:MA at sensitized acupoints could elevate PPT of KOA patients,which may be associated with the increment of SC and BP.

Nitric Oxide Signaling Molecules in Acupoints:Toward Mechanisms of Acupuncture

Recent clinical trial studies have demonstrated that the effects of acupuncture on pain improvement are small and no difference between acupoints and non-points. Whether acupuncture needles must be inserted in specific points depends on whether acupoint specificity exists that is still not resolved, and is now urgent. Previous anatomical studies have demonstrated that acupoints exist higher number of nerve fibers/trunks, blood vessels, hair follicles, and sweat glands as well as density of the gap junction. Recent evidence shows that nitric oxide（NO） level is elevated in the acupoints/meridians and is associated with an enhanced expression of NO synthase endowed with transient receptor potential vanilloid type-1. There is growing evidence from international groups showing that acupuncture induces NO-mediated vasodilatation, which increases local blood flow and allows for a flush of algesic or sensitizing substances, leading to pain relief. Previous studies, using a novel biocapture system, have demonstrated that NOx–（total nitrite and nitrate） and cyclic guanosine monophosphate（c GMP） concentrations are consistently increased over skin acupoints compared to non-meridian control regions（NMCR） in humans. Dermal microdialysis in humans showed that NO-c GMP releases in the subcutaneous tissue of acupoint are higher than those in NMCR and increased by electroacupuncture（EA）. Recent studies have demonstrated that low-frequency electrical stimulation and manual acupuncture with low stimulating force and rate produce an elevation of NO release predominantly over acupoints. In contrast, NO levels over the areas of the skin regions are moderately reduced by high-frequency EA stimulation. The results from anatomical and biochemical studies consistently show that acupoints exist higher levels of NO signaling molecules, and stimulus-evoked NO release is also with a higher level at acupoints. Results suggest that NO signaling molecules contribute to the specificity of acupoints, and selecting well-trained acupuncturetists for using correct acupoints and appropriate parameters should improve acupuncture clinical trial studies.

单盲双模拟针灸临床试验设计思路与实践——以“手针和电针治疗绝经烘热疗效比较”研究为例

Randomized controlled trial(RCT)is the golden standard for evaluation of clinical evidence.To assess the effect of acupuncture,due to the specificity of acupuncture intervention,the blinding and control methods are the difficulties in study design.It is not practical to blind investigators,participants and evaluators simultaneously.At present,blinding is generally conducted for the participants and evaluators in clinical trial.We took a comparative study of manual acupuncture and electroacupuncture for menopausal hot flush as an example to explore a new way with the reference of double-dummy design in new drug study.A single-blind and double-dummy clinical trial model of acupuncture was established.Based on individual acupuncture intervention in each group,the placebo intervention was combined to ensure the form consistency of two groups.Such a study design may eliminate non-specific effect of acupuncture,and can be conductive to comparing the specific effect of acupuncture and can provide the references and regimens for study design.

针药并举干预精神分裂症后抑郁共病失眠:一项基于JBI报告清单的回顾性系列病例研究

Background:Acupuncture combined with Chinese herbal medicine was performed on 24 patients with post-schizophrenia comorbid depressive disorder and insomnia admitted to the Psychiatry Department,Shanghai Municipal Hospital of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine from 2016 to 2020,and provided satisfactory results.Considering post-schizophrenia comorbid depressive disorder and insomnia is not a common clinical disorder in hospital of traditional Chinese medicine,the treatment and follow-up cycle is long,and the dropout rate is high,a retrospective case series based on Joanna Briggs Institute(JBI) reporting checklist were conducted instead of a randomized controlled trial.Objective:To retrospectively summary the short-,mid-and long-term effects of acupuncture combined with Chinese herbal medicine for post-schizophrenia comorbid depressive disorder and insomnia,and analyze the principles of the prescriptions.Methods:A retrospective analysis based on case series JBI reporting checklist were performed to investigate effects of 24 patients with post-schizophrenia comorbid depressive disorder and insomnia undergoing 12-week combined acupuncture and Chinese herbal medicine treatment(patients did not receive full dosage treatments,or received western medicine or other physical and psychological therapies during the treatment period were excluded).The psychotic symptoms,depression,insomnia,and self-care ability for daily living were measured by the Positive and Negative Syndrome Scale(PANSS),Calgary Depression Scale for Schizophrenia(CDSS),Pittsburgh Sleep Quality Index(PSQI),and Activity of Daily Living Questionnaire(ADL-Q),respectively.Follow-ups were conducted at 8 and 16 weeks after treatment.Meanwhile,Acupuncture Beliefs Scale(ABS) was assessed at pre-and post-treatment as well as 16-week follow-up to investigate patients’ beliefs and expectations for acupuncture treatment.Results:(1) compared with pre-treatment,the PANSS global scores did not decrease significantly at posttreatment and follow-up periods(P> 0.05).(2) compared with pre-treatment,the global scores of CDSS and PSQI decreased significantly at post-treatment and follow-up periods(both P<0.05).The PSQI global scores at the 16-week follow-up were even significantly lower than at port-treatment(P<0.05).(3) after treatment,the ADL-Q.global scores decreased significantly(P<0.05),and continued to decrease during the follow-ups(P<0.05).(4) effective treatment improved patients’ beliefs and expectations of acupuncture therapy.Conclusions:Acupuncture combined with Chinese herbal medicine can significantly improve the insomnia and depressed mood following schizophrenia,with satisfactory short-,medium-and long-term effects;effective treatment experience can increase patients’ beliefs and expectations for acupuncture therapy.