Acupuncture modulates temporal neural responses in wide brain networks: evidence from fMRI study

<p>Abstract</p> <p>Background</p> <p>Accumulating neuroimaging studies in humans have shown that acupuncture can modulate a widely distributed brain network, large portions of which are overlapped with the pain-related areas. Recently, a striking feature of acupuncture-induced analgesia is found to be associated with its long-last effect, which has a delayed onset and gradually reaches a peak even after acupuncture needling being terminated. Identifying temporal neural responses in these areas that occur at particular time -- both acute and sustained effects during acupuncture processes -- may therefore shed lights on how such peripheral inputs are conducted and mediated through the CNS. In the present study, we adopted a non-repeated event-related (NRER) fMRI paradigm and control theory based approach namely change-point analysis in order to capture the detailed temporal profile of neural responses induced by acupuncture.</p> <p>Results</p> <p>Our findings demonstrated that neural activities at the different stages of acupuncture presented distinct temporal patterns, in which consistently positive neural responses were found during the period of acupuncture needling while much more complex and dynamic activities found during a post-acupuncture period. These brain responses had a significant time-dependent effect which showed different onset time and duration of neural activities. The amygdala and perigenual anterior cingulate cortex (pACC), exhibited increased activities during the needling phase while decreased gradually to reach a peak below the baseline. The periaqueductal gray (PAG) and hypothalamus presented saliently intermittent activations across the whole fMRI session. Apart from the time-dependent responses, relatively persistent activities were also identified in the anterior insula and prefrontal cortices. The overall findings indicate that acupuncture may engage differential temporal neural responses as a function of time in a wide range of brain networks.</p> <p>Conclusions</p> <p>Our study has provided evidence supporting a view that acupuncture intervention involves complex modulations of temporal neural response, and its effect can gradually resolve as a function of time. The functional specificity of acupuncture at ST36 may involve multiple levels of differential activities of a wide range of brain networks, which are gradually enhanced even after acupuncture needle being terminated.</p

Electroacupuncture Inhibits Inflammation Reaction by Upregulating Vasoactive Intestinal Peptide in Rats with Adjuvant-Induced Arthritis

Acupuncture is emerging as an alternative therapy for rheumatoid arthritis (RA). However, the molecular mechanism underlying this beneficial effect of acupuncture has not been fully understood. Here, we demonstrated that electroacupuncture at acupoints Zusanli (ST36), Xuanzhong (GB39); and Shenshu (BL23) markedly decreased the paw swelling and the histologic scores of inflammation in the synovial tissue, and reduced the body weight loss in an adjuvant-induced arthritis rat model. However, the electrical stimulation at nonacupoint did not produce any beneficial effects against the experimental arthritis. Most interestingly, the electroacupuncture treatment resulted in an enhanced immunostaining for vasoactive intestinal peptide (VIP), a potent anti-inflammatory neuropeptide, in the synovial tissue. Moreover, the VIP-immunostaining intensity was significantly negatively correlated with the scores of inflammation in the synovial tissue (r = −0.483, P = .0026). In conclusion, these findings suggest that electroacupuncture may offer therapeutic benefits for the treatment of RA, at least partially through the induction of VIP expression

Assessing the Effects of Acupuncture by Comparing Needling the Hegu Acupoint and Needling Nearby Nonacupoints by Spectral Analysis of Microcirculatory Laser Doppler Signals

We aimed to assess the effects of acupuncture by analyzing the frequency content of skin blood-flow signals simultaneously recorded at the Hegu acupoint and two nearby nonacupoints following acupuncture stimulation (AS). Laser Doppler flowmetry (LDF) signals were measured in male healthy volunteers in two groups of experiments: needling the Hegu acupoint (n = 13) and needling a nearby nonacupoint (control experiment; n = 10). Each experiment involved recording a 20 min baseline-data sequence and two sets of effects data recorded 0–20 and 50–70 min after stopping AS. Wavelet transform with Morlet mother wavelet was applied to the measured LDF signals. Needling the Hegu acupoint significantly increased the blood flow, significantly decreased the relative energy contribution at 0.02–0.06 Hz and significantly increased the relative energy contribution at 0.4–1.6 Hz at Hegu, but induced no significant changes at the nonacupoints. Also, needling a nearby nonacupoint had no effect in any band at any site. This is the first time that spectral analysis has been used to investigate the microcirculatory blood-flow responses induced by AS, and has revealed possible differences in sympathetic nerve activities between needling the Hegu acupoint and its nearby nonacupoint. One possible weakness of the present design is that different De-Qi feelings following AS could lead to nonblind experimental setup, which may bias the comparison between needling Hegu and its nearby nonacupoint. Our results suggest that the described noninvasive method can be used to evaluate sympathetic control of peripheral vascular activity, which might be useful for studying the therapeutic effects of AS

Manual Acupuncture at PC6 Ameliorates Acute Restraint Stress-Induced Anxiety in Rats by Normalizing Amygdaloid Noradrenergic Response

Acupuncture improves ethanol withdrawal-induced anxiety in rats in an acupoint-dependent manner. Thus, the present study investigated the effects of acupuncture on acute restraint stress- (ARS-) induced anxiety. Male rats were exposed to ARS for 3 h followed by acupuncture at either PC6 (Neiguan), HT7 (Shenmen), or a nonacupoint (tail) once a day for three consecutive days. Five minutes after the third acupuncture treatment, anxiety-like behavior was evaluated in an elevated plus maze (EPM). Additionally, plasma corticosterone (CORT) levels were measured by radioimmunoassay and the concentrations of norepinephrine (NE) and 3-methoxy-4-hydroxy-phenylglycol (MHPG) in the central nucleus of the amygdala (CeA) were determined using high-performance liquid chromatography. Acupuncture at PC6, but not HT7 or a nonacupoint, attenuated anxiety-like behavior, but this attenuation was abolished by a postacupunctural intra-CeA infusion of NE. Acupuncture at PC6 also reduced the oversecretion of plasma CORT and inhibited increases in amygdaloid NE and MHPG induced by ARS. Further, Western blot analyses and real-time polymerase chain reaction assays revealed that acupuncture at PC6 prevented ARS-induced enhancements in the protein and mRNA expressions of tyrosine hydroxylase in the CeA. These results suggest that acupuncture performed specifically at acupoint PC6 reduces ARS-induced anxiety-like behavior by dampening amygdaloid noradrenergic responses

A Correlation Study between Two Adjacent Same-Meridian Acupoints after Laser-Needle Acupuncture with Optical Coherence Tomography and Diffuse Reflectance Spectra

This study is to investigate the correlations among Sanjian (LI3), Hegu (LI4), and Yangxi (LI5) acupoints and their corresponding nonacupoints on the Yangming Large Intestine Meridian of Hand before and after laser irradiation using optical coherence tomography (OCT) and diffuse reflectance spectra. The experiment was conducted on 10 healthy people. A 658 nm laser with 50 mW output power was used for irradiating LI4, LI5 acupoints and their corresponding nonacupoints. As to LI4 acupoint with laser irradiation for duration of 15 or 45 minutes, the OCT backscattered light intensities of LI4 and LI5 acupoints increased significantly, and the reflectance intensities (RIs) of the LI3, LI4, and LI5 acupoints decreased significantly. As to LI5 acupoint with laser irradiation for duration of 15 or 45 minutes, the changes of OCT backscattered light intensities of the corresponding irradiated acupoint and LI4 acupoint increased significantly, and the RIs decreased significantly. However, the OCT backscattered light intensities and RIs for their nonacupoints were almost not changed. The results show that an association exists between two adjacent same-meridian acupoints on the same meridian after laser-needle acupuncture to some extent

Acupuncture Stimulation Alleviates Corticosterone-Induced Impairments of Spatial Memory and Cholinergic Neurons in Rats

The purpose of this study was to examine whether acupuncture improves spatial cognitive impairment induced by repeated corticosterone (CORT) administration in rats. The effect of acupuncture on the acetylcholinergic system was also investigated in the hippocampus. Male rats were subcutaneously injected with CORT (5 mg/kg) once daily for 21 days. Acupuncture stimulation was performed at the HT7 (Sinmun) acupoint for 5 min before CORT injection. HT7 acupoint is located at the end of transverse crease of ulnar wrist of forepaw. In CORT-treated rats, reduced spatial cognitive function was associated with significant increases in plasma CORT level (+36%) and hippocampal CORT level (+204%) compared with saline-treated rats. Acupuncture stimulation improved the escape latency for finding the platform in the Morris water maze. Consistently, the acupuncture significantly alleviated memory-associated decreases in cholinergic immunoreactivity and mRNA expression of BDNF and CREB in the hippocampus. These findings demonstrate that stimulation of HT7 acupoint produced significant neuroprotective activity against the neuronal impairment and memory dysfunction

MicroRNA Profiling Response to Acupuncture Therapy in Spontaneously Hypertensive Rats

MicroRNAs (miRNAs) are a group of endogenous noncoding RNAs that play important roles in many biological processes. This study aimed to check if miRNAs were involved in the response to acupuncture in rats. Microarray analysis was performed to compare the miRNA expression profiles of medulla in spontaneously hypertensive rats (SHRs) treated with or without acupuncture. Our microarray analysis identified 222 differentially expressed miRNAs in the medulla of SHRs treated with acupuncture at taichong acupoint. Among these miRNAs, 23 miRNAs with a significant difference were found in acupuncture-treated SHRs compared to untreated rats. These 23 miRNAs could regulate 2963 target genes which were enriched in at least 14 pathways based on our bioinformatic analysis. miRNA-339, miR-223, and miR-145 were downregulated in the medulla of SHRs compared to normotensive rats. Notably, these miRNAs were upregulated to basal levels in the medulla of SHRs treated with acupuncture at taichong in comparison with SHRs receiving acupuncture at nonacupoint group or SHRs without any treatment. Our findings have revealed significant changes of a panel of selective miRNAs in hypertensive rats treated at taichong acupoint. These data provide insights into how acupuncture elicits beneficial effects on hypertension

Acupuncture Stimulation Attenuates Impaired Emotional-Like Behaviors and Activation of the Noradrenergic System during Protracted Abstinence following Chronic Morphine Exposure in Rats

The purpose of this study was to evaluate whether acupuncture stimulation attenuates withdrawal-induced behaviors in the rats during protracted abstinence following chronic morphine exposure. To do this, male rats were first exposed to morphine gradually from 20 to 100 mg/kg for 5 days, and subsequently naloxone was injected once to extend despair-related withdrawal behaviors for 4 weeks. Acupuncture stimulation was performed once at the SP6 (Sanyinjiao) acupoint on rat’s; hind leg for 5 min during protracted abstinence from morphine. The acupuncture stimulation significantly decreased despair-like behavior deficits in the forced swimming test and low sociability in the open-field test as well as increased open-arm exploration in the elevated plus maze test in the last week of 4-week withdrawal period. Also the acupuncture stimulation significantly suppressed the increase in the hypothalamic corticotropin-releasing factor (CRF) expression, the decrease in the tyrosine hydroxylase expression in the locus coeruleus, and the decrease in the hippocampal brain-derived neurotrophic factor mRNA expression, induced by repeated injection of morphine. Taken together, these findings demonstrate that the acupuncture stimulation of SP6 significantly reduces withdrawal-induced behaviors, induced by repeated administration of morphine in rats, possibly through the modulation of hypothalamic CRF and the central noradrenergic system