Deep electroacupuncture of neurogenic spots attenuates immobilization stress-induced acute hypertension in rats.

Background: Our previous studies proved that neurogenic inflammatory spots (or neurogenic spots) have the same physiological features as acupuncture points and that neurogenic spot stimulation generates therapeutic effects in various animal models. However, it is unclear how deeply the neurogenic spots should be stimulated to generate therapeutic effects. Methods: The effects of acupuncture at various needle depths below the neurogenic spot were examined in a rat immobilization stress-induced hypertension (IMH) model. Electroacupuncture was applied to a neurogenic spot at depths of 1, 2, or 3 mm using a concentric bipolar electrode. Results: Electrical stimulation of the neurogenic spot at a 3-mm depth most effectively lowered blood pressure compared with controls and stimulation at 1- and 2-mm depths, which was inhibited by pretreatment with a local anesthetic lidocaine. Electrical stimulation of the neurogenic spot or injection of substance P (SP) at a 3-mm depth significantly excited the rostral ventrolateral medulla (rVLM) compared with superficial stimulation. Electrical stimulation applied at a 3-mm depth on neurogenic spots dominantly caused c-fos expression from rVLM and ventrolateral periaqueductal gray (vlPAG) in IMH rats. Pretreatment with resiniferatoxin (RTX) injection into the neurogenic spot to ablate SP or calcitonin gene-related peptide (CGRP) prevented the effects of 3-mm neurogenic spot stimulation on blood pressure in IMH rats. Conversely, artificial injection of SP or CGRP generated anti-hypertensive effects in IMH rats. Conclusion: Our data suggest that neurogenic spot stimulation at a 3-mm depth generated anti-hypertensive effects through the local release of SP and CGRP and activation of rVLM and vlPAG.

What is the analgesic range of acupuncture stimulus for treating acute pain?

Introduction: Since the analgesic effect of acupuncture stimulation is derived from different mechanisms depending on the type of pain, it is important to know which acupuncture points to stimulate. In this study, to confirm the effect of acupuncture stimulation on acute pain from a neurological point of view, somatosensory evoked potential and sensory threshold changes were evaluated to identify the nerve range that is affected by acupuncture stimulation on LI4 (Hapgok acupuncture point, of the radial nerve) during acute pain. Methods: The subjects were 40 healthy men and women aged 19-35 years. The study was designed as a randomly controlled, crossover trial with acupuncture stimulation at LI4 as the intervention. The washout period for acupuncture stimulation was 2 weeks, and the subjects were divided into two groups, i.e., an acupuncture stimulation group and a nonstimulation group, with 10 men and 10 women in each group. Somatosensory evoked potential measurement was carried out for 5 min by alternately applying 2 HZ-pulse electrical stimulation to the thumb and the little finger of the hand acupunctured with a 64-channel electroencephalogram. The verbal rating scale was used before and after each acupuncture stimulation session. Result and discussion: The results of the study confirmed that the somatosensory evoked potential amplitude value of the thumb was significantly decreased and that the intensity of sensory stimulation corresponding to a verbal rating scale score of 6 was significantly increased only in the thumb after acupuncture stimulation. Therefore, the results show that acupuncture treatment for acute pain is more effective when direct acupuncture stimulation is applied to the painful area.

Mediation of mPFC-LHb pathway in acupuncture inhibition of cocaine psychomotor activity.

The medial prefrontal cortex (mPFC) and the lateral habenula (LHb) play roles in drug addiction and cognitive functions. Our previous studies have suggested that acupuncture at Shenmen (HT7) points modulates mesolimbic reward system in order to suppress drug-induced addiction behaviours. To explore whether an mPFC-LHb circuit mediates the inhibitory effects of acupuncture on addictive behaviours, we examined the projection from mPFC to LHb, excitation of mPFC neurons during acupuncture stimulation, the effects of optogenetic modulation of mPFC-LHb on HT7 inhibition of cocaine-induced locomotion and the effect of mPFC lesion on HT7 inhibition of nucleus accumbens (NAc) dopamine release. Acupuncture was applied at bilateral HT7 points for 20 s, and locomotor activity was measured in male Sprague-Dawley rats. Although cocaine injection significantly increased locomotor activity, HT7 acupuncture suppressed the cocaine-induced locomotion. The inhibitory effect of HT7 on cocaine-enhanced locomotion was blocked by optogenetic silencing of the mPFC-LHb circuit. In vivo extracellular recordings showed that HT7 acupuncture evoked an increase in the action potentials of mPFC neurons. Optopatch experiment proved glutamatergic projections from mPFC to LHb. HT7 acupuncture suppressed NAc dopamine release following cocaine injection, which was blocked by electrolytic lesion of mPFC. These results suggest the mediation of mPFC-LHb circuit in the inhibitory effects of acupuncture on cocaine psychomotor activity in rats.

Acupuncture treatment for functional gastrointestinal disorders: Identification of major acupoints using network analysis.

Background: Using network analysis, we sought to determine the acupoints most commonly used to treat functional gastrointestinal disorders (FGIDs), particularly functional dyspepsia (FD) and irritable bowel syndrome (IBS). Methods: To explore the acupoint patterns used for FGID, data on acupoint combinations for FD and IBS were gathered from systematic reviews. Network analysis was used to determine the degree, closeness centrality, betweenness centrality, and eigenvector centrality of each acupoint. The most common acupoint combinations for FD and IBS were examined based on the eigenvector centrality. Results: Network analysis revealed that CV12, ST25, ST36, CV10, and LR3, which had the highest eigenvector centrality values, were the main acupoints for treating FGID. CV12 was the main acupoint for treating FD, while ST25 was the hub acupoint for treating IBS in the abdomen. ST36, LR3, and PC6 were the key peripheral acupoints for FD and IBS. Conclusions: Using network analysis, we provided data that will aid the selection of both general and specific acupoints for FD and IBS, along with spatial information (i.e., the positions of acupoints on a body map). These findings could be applied in future acupuncture research on therapy for gastrointestinal system dysfunction. They may also help bridge the gap between the traditional meridian theory, which assumes that there is a link between diseases/symptoms and the specific body region being treated, and real-world clinical evidence.

Analgesic efficacy of median nerve stimulation in mice with chemotherapy-induced peripheral neuropathymodulation of brain-derived neurotrophic factor expression.

OBJECTIVE: Chemotherapeutic agents such as docetaxel (DTX) can trigger chemotherapy-induced peripheral neuropathy (CIPN), which is characterized by unbearable pain. This study was designed to investigate the analgesic effect and related neuronal mechanism of low-frequency median nerve stimulation (LFMNS) on DTX-induced tactile hypersensitivity in mice. METHODS: To produce CIPN, DTX was administered intraperitoneally 4 times, once every 2 d, to male ICR mice. LFMNS was performed on the wrist area, and the pain response was measured using von Frey filaments on both hind paws. Western blot and immunofluorescence staining were performed using dorsal root ganglion and spinal cord samples to measure the expression of brain-derived neurotrophic factor (BDNF). RESULTS: Repeated LFMNS significantly attenuated the DTX-induced abnormal sensory response and suppressed the enhanced expression of BDNF in the DRG neurons and spinal dorsal area. CONCLUSIONS: LFMNS might be an effective non-pharmaceutical option for treating patients suffering from CIPN regulating the expression of peripheral and central BDNF.

Attenuation of immobilization stress-induced hypertension by temperature-controllable warm needle acupuncture in rats and the peripheral neural mechanisms.

Introduction: We and others have shown that electrical stimulation of the PC-6 acupoint over the wrist relieves hypertension by stimulating afferent sensory nerve fibers and activating the central endogenous opioid system. Warm needle acupuncture has long been utilized to treat various diseases in clinics. Methods: Here, we developed a temperature-controllable warm needle acupuncture instrument (WAI) and investigated the peripheral mechanism underlying the effect of warm needle acupuncture at PC-6 on hypertension in a rat model of immobilization stress-induced hypertension. Results: Stimulation with our newly developed WAI and traditional warm needle acupuncture attenuated hypertension development. Such effects were reproduced by capsaicin (a TRPV1 agonist) injection into PC-6 or WAI stimulation at 48°C. In contrast, PC-6 pretreatment with the TRPV1 antagonist capsazepine blocked the antihypertensive effect of WAI stimulation at PC-6. WAI stimulation at PC-6 increased the number of dorsal root ganglia double-stained with TRPV1 and CGRP. QX-314 and capsaicin perineural injection into the median nerve for chemical ablation of small afferent nerve fibers (C-fibers) prevented the antihypertensive effect of WAI stimulation at PC-6. Additionally, PC-6 pretreatment with RTX ablated the antihypertensive effect of WAI stimulation. Conclusion: These findings suggest that warm needle acupuncture at PC-6 activates C-fiber of median nerve and the peripheral TRPV1 receptors to attenuate the development of immobilization stress-induced hypertension in rats.

Electroacupuncture stimulation of HT7 alleviates sleep disruption following acute caffeine exposure by regulating BDNF-mediated endoplasmic reticulum stress in the rat medial septum.

Acupuncture stimulation can protect the brain against caffeine-induced sleep disruption. This study investigated whether electroacupuncture stimulation acupuncture point HT7 alleviates sleep disruption by regulating mBDNF and ER stress in the medial septum. Acute exposure to caffeine (15 mg/kg, i.p.) increased the wake time and decreased REM sleep, which HT7 stimulation alleviated. HT7 stimulation ameliorated the acute caffeine exposure-induced increase in the expression of BiP, an endoplasmic reticulum stress response protein, in the rat medial septum. Interestingly, HT7 stimulation induced the expression of mBDNF and pTrkB in the medial septum. The next experiment investigated whether TrkB phosphorylated by HT7 stimulation induced BiP expression in the rat medial septum. Before electroacupuncture stimulation at HT7, ANA-12 was administered to caffeine-treated rats. In rats administered ANA-12 in the medial septum, HT7 stimulation did not reduce BiP expression. These findings suggest that HT7 stimulation improves wake time and REM sleep dysfunction by regulating the BDNF-mediated endoplasmic reticulum stress response in the medial septum. These results indicate that the alleviation of endoplasmic reticulum stress in the medial septum by HT7 stimulation and the subsequent amelioration of insomnia may depend on phosphorylated TrkB activation.

Biopotential changes of acupuncture points by acupuncture stimulation.

Background: The energy flow at acupuncture point is important for understanding the mechanism of acupuncture treatment. However, there are few studies on energy at acupuncture point, and related studies have limitation in explaining the energy flow in all meridians. Thus, we aimed to understand the properties of electrical energy at acupuncture point in twelve meridians by measuring the biopotential at acupuncture and non-acupuncture points. Methods: For each meridian, twenty subjects were participated, and biopotential was measured at five transport points and their adjacent non-acupuncture points. In each subject, both 'non-stimulation' and 'stimulation' experiments were conducted in random order. The data were analyzed in two parts: biopotential variability and biopotential difference between acupuncture and non-acupuncture points. Results: The biopotential variability at acupuncture point was increased by acupuncture stimulation, and it was related to the activation of Qi flow by acupuncture stimulation. The biopotential difference between acupuncture and non-acupuncture points was formed in the direction related to the Qi flow theory, and this biopotential difference tended to decrease by acupuncture stimulation. Conclusion: The study on biopotential can provide a foundation for research on energy flow mechanism of acupuncture stimulation, and it is expected to overcome limitation of qualitative explanation in traditional medicine.

Acupuncture Regulates Symptoms of Parkinson's Disease via Brain Neural Activity and Functional Connectivity in Mice.

Parkinson's disease (PD) is a multilayered progressive brain disease characterized by motor dysfunction and a variety of other symptoms. Although acupuncture has been used to ameliorate various symptoms of neurodegenerative disorders, including PD, the underlying mechanisms are unclear. Here, we investigated the mechanism of acupuncture by revealing the effects of acupuncture treatment on brain neural responses and its functional connectivity in an animal model of PD. We observed that destruction of neuronal network between many brain regions in PD mice were reversed by acupuncture. Using machine learning analysis, we found that the key region associated with the improvement of abnormal behaviors might be related to the neural activity of M1, suggesting that the changes of c-Fos in M1 could predict the improvement of motor function induced by acupuncture treatment. In addition, acupuncture treatment was shown to significantly normalize the brain neural activity not only in M1 but also in other brain regions related to motor behavior (striatum, substantia nigra pars compacta, and globus pallidus) and non-motor symptoms (hippocampus, lateral hypothalamus, and solitary tract) of PD. Taken together, our results demonstrate that acupuncture treatment might improve the PD symptoms by normalizing the brain functional connectivity in PD mice model and provide new insights that enhance our current understanding of acupuncture mechanisms for non-motor symptoms.

Diachronic analysis of major acupoints used in ancient and current acupuncture treatments: Changes in main acupoints over time.

Background: Over time, a large body of knowledge on acupoint selection patterns has accumulated. This study compared the main acupoint selection patterns between ancient and current acupuncture treatments. Methods: Data on the 10 most frequently used acupoints were obtained from a current medical database, the Cochrane Database of Systematic Reviews, and the ancient medical text Donguibogam. Network analysis was used to identify the most commonly used major points across various diseases. Results: The most commonly used acupoints in both ancient and current acupuncture were ST36, SP6, LR3, LI4, and GV20. Acupoints CV3, CV4, CV6, CV8, and CV12 were more widely used in ancient acupuncture, while in current acupuncture, HT7, PC6, KI3, GB34, and EX-HN3 were more prevalent. Conclusions: Ancient and current acupuncture practice had similar and distinct acupoint selection patterns. Diachronic analysis sheds light on how patterns of acupoint selection have changed.

Role of Lateral Hypothalamus in Acupuncture Inhibition of Cocaine Psychomotor Activity.

Acupuncture modulates the mesolimbic dopamine (DA) system; an area implicated in drug abuse. However, the mechanism by which peripheral sensory afferents, during acupuncture stimulation, modulate this system needs further investigation. The lateral hypothalamus (LH) has been implicated in reward processing and addictive behaviors. To investigate the role of the LH in mediating acupuncture effects, we evaluated the role of LH and spinohypothalamic neurons on cocaine-induced psychomotor activity and NAc DA release. Systemic injection of cocaine increased locomotor activity and 50 kHz ultrasonic vocalizations (USVs), which were attenuated by mechanical stimulation of needles inserted into HT7 but neither ST36 nor LI5. The acupuncture effects were blocked by chemical lesions of the LH or mimicked by activation of LH neurons. Single-unit extracellular recordings showed excitation of LH and spinohypothalamic neurons following acupuncture. Our results suggest that acupuncture recruits the LH to suppress the mesolimbic DA system and psychomotor responses following cocaine injection.

The Role of Skin Mast Cells in Acupuncture Induced Analgesia in Animals: A Preclinical Systematic Review and Meta-analysis.

While mast cells (MCs) are previously well-known as a pathological indicator of pain, their role in alleviating pain is recently emerged in acupuncture research. Thus, this study systematically reviews the role of MC in acupuncture analgesia. Animal studies on MC changes associated with the acupuncture analgesia were searched in PubMed and EMBASE. The MC number, degranulation ratio and pain threshold changes were collected as outcome measures for meta-analyses. Twenty studies were included with 13 suitable for meta-analysis, most with a moderate risk of bias. A significant MC degranulation after acupuncture was indicated in the normal and was significantly higher in the pain model. In the subgroup analysis by acupuncture type, manual (MA) and electrical (EA, each P < .00001) but not sham acupuncture had significant MC degranulation. Meta-regression revealed the linear proportionality between MC degranulation and acupuncture-induced analgesia (P < .001), which was found essential in MA (P < .00001), but not in EA (P = .45). MC mediators, such as adenosine and histamine, are involved in its mechanism. Taken together, skin MC is an essential factor for acupuncture-induced analgesia, which reveals a new aspect of MC as a pain alleviator. However, its molecular mechanism requires further study. PERSPECTIVE: This systematic review synthesizes data from studies that examined the contribution of skin MC in acupuncture analgesia. Current reports suggest a new role for skin MC and its mediators in pain alleviation and explain a peripheral mechanism of acupuncture analgesia, with suggesting the need of further studies to confirm these findings.

Ultrasonic device developed for non-invasive moxibustion therapy.

BACKGROUND: Recently, some adverse effects of moxibustion has been reported such as burns, smoke, allergies, and so on. To overcome the adverse effects of traditional moxibustion, an ultrasonic moxibustion device (UMD) was designed, simulated, fabricated, and tested. The objective of this study is to provide detailed information about the main design parameters, simulation outcome, and performance-test results. METHODS: The main components of the UMD are a 1-MHz ultrasonic transducer (UT) with concave lens, and its applicator. The acoustic pressure and temperature distribution of the UT was simulated and described graphically using COMSOL software, which is based on the finite element method (FEM). Experimental verification of the temperature distribution was performed on the skin of pork. The temperature-change profiles of pork in relation to increase of therapy time were obtained at an unfocused point (2 mm) and at a focal distance of 13 mm. For the performance test, moxibustion therapy was conducted on the abdominal skin of mice for 120 min using the new UMD and its histological images were acquired to analyze the skin-tissue damage. RESULTS: The FEM simulation of temperature distribution and acoustic pressure agreed with the experimental outcome. Histological images showed that there was no skin-tissue damage to the mouse abdomens after therapy. The results clearly show that the newly developed UMD can overcome the disadvantages of traditional moxibustion therapy and achieve the proposed design parameters. CONCLUSION: The FEM simulation and performance tests provided valuable information about developing future UMDs. In addition, its performance can be compared with traditional moxibustion therapy for future study.

Acupuncture reduces cocaine psychomotor responses by activating the rostromedial tegmental nucleus.

The rostromedial tegmental nucleus (RMTg), a GABAergic afferent to midbrain dopamine (DA) neurons, has emerged as an integral player in both rewarding and nociceptive responses. While previous studies have demonstrated that acupuncture modulates DA transmission in the mesolimbic reward system originating in the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAc) and can reduce drug self-administration, the central links between peripheral acupuncture signals and brain reward systems are not well-characterized. Thus, we hypothesised that acupuncture would elicit inhibitory signals from RMTg neurons to brain reward systems. Acupuncture reduced acute cocaine-induced locomotor activity and DA release in a point-specific manner, which was blocked by optogenetic silencing or chemical lesion of the RMTg. The acupuncture effect was mimicked by chemical activation of the RMTg. Acupuncture activated RMTg GABA neurons. In addition, the inhibitory effects of acupuncture on acute cocaine-induced locomotor activity were prevented by electrolytic lesions of the lateral habenula (LHb) or fasciculus retroflexus (FR), areas known to project to the RMTg. These findings suggest that acupuncture recruits the RMTg to reduce the psychomotor responses enhanced by acute cocaine.

Acupuncture stimulation at HT7 as a non-pharmacological therapy for sleep disorder caused by caffeine administration in rats.

OBJECTIVES: Insomnia is one of the most common sleep disorders and is difficult to completely treat because of the undesirable side effects of hypnotics. The present study was designed to investigate the hypnotic effect of acupuncture stimulation at HT7 on caffeine-induced sleep disorders and locomotor activity in rats. We also evaluated neuronal activity changes in the arousal region of the basal forebrain. METHODS: Rats received intraperitoneal injections of caffeine, and then electroencephalogram power spectrum analysis and locomotor activity measurements were performed. Stimulation at HT7 was performed using a mechanical acupuncture instrument (MAI) before caffeine injection, and its effects on caffeine-induced changes in sleep architecture, locomotor activity and c-Fos expression were examined. RESULTS: Caffeine injection (7.5 mg/kg) produced a significant decrease in slow-wave sleep and an increase in wake time compared with saline injection. Caffeine injection also increased locomotor activity and c-Fos expression in the medial septum-vertical limb of the diagonal band of Broca (MS-VDB), one of the arousal regions of the basal forebrain. Stimulation at HT7 with the MAI alleviated the caffeine-induced sleep disturbance and the increase in locomotor activity. In addition, MAI treatment at HT7, compared with treatment at a location not corresponding to any traditional acupuncture point, reduced the caffeine-induced increase in c-Fos expression. CONCLUSION: These results indicate that the hypnotic effect of HT7 acupuncture stimulation on caffeine-induced insomnia was associated with suppression of neuronal activity in the basal forebrain.

Electroacupuncture at Neurogenic Spots in Referred Pain Areas Attenuates Hepatic Damages in Bile Duct-Ligated Rats.

Visceral pain frequently produces referred pain at somatic sites due to the convergence of somatic and visceral afferents. In skin overlying the referred pain, neurogenic spots characterized by hyperalgesia, tenderness and neurogenic inflammation are found. We investigated whether neurogenic inflammatory spots function as acupoints in the rat model of bile duct ligation-induced liver injury. The majority of neurogenic spots were found in the dorsal trunk overlying the referred pain and matched with locations of acupoints. The spots, as well as acupoints, showed high electrical conductance and enhanced expression of the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP). Electroacupuncture at neurogenic spots reduced serum hepatocellular enzyme activities and histological patterns of acute liver injury in bile duct ligation (BDL) rats. The results suggest that the neurogenic spots have therapeutic effects as acupoints on hepatic injury in bile-duct ligated rats.

Peripheral ERK modulates acupuncture-induced brain neural activity and its functional connectivity.

Acupuncture has been widely used as a therapeutic intervention, and the brain network plays a crucial role in its neural mechanism. This study aimed to investigate the acupuncture mechanism from peripheral to central by identifying how the peripheral molecular signals induced by acupuncture affect the brain neural responses and its functional connectivity. We confirmed that peripheral ERK activation by acupuncture plays a role in initiating acupuncture-induced peripheral proteomic changes in mice. The brain neural activities in the neocortex, hippocampus, thalamus, hypothalamus, periaqueductal grey, and nucleus of the solitary tract (Sol) were significantly changed after acupuncture, and these were altered by peripheral MEK/MAPK inhibition. The arcuate nucleus and lateral hypothalamus were the most affected by acupuncture and peripheral MEK/MAPK inhibition. The hypothalamic area was the most contributing brain region in contrast task PLS analysis. Acupuncture provoked extensive changes in brain functional connectivity, and the posterior hypothalamus showed the highest betweenness centrality after acupuncture. After brain hub identification, the Sol and cingulate cortex were selected as hub regions that reflect both degree and betweenness centrality after acupuncture. These results suggest that acupuncture activates brain functional connectivity and that peripheral ERK induced by acupuncture plays a role in initiating brain neural activation and its functional connectivity.

The effect of acupuncture stimulation on alleviating emotional changes due to acute alcohol administration and the possibility of sigma1 receptor involvement.

BACKGROUND: Most ETOH addiction preclinical studies have focused on the rewards of chronic ETOH self-administration or the ETOH reinstatement model. Acute ETOH administration studies are scarce despite the potential of ETOH to cause sedation, intoxication and reduced acute functional tolerance. Here, we established a rat model of acute ETOH administration induced by an intraperitoneal injection of 1 g/kg ethanol and assessed the similarities in physiological and behavioral effects between acupuncture and Sigma1 R antagonists. METHODS: Male Wistar rats (300-330 g) received pretreatment with (1) saline injection, (2) saline + mechanical stimulation using a mechanical acupuncture instrument (MAI) for acupuncture at the Shenmen (HT7), (3) ETOH (1 g/kg) injection, (4) ETOH + HT7, or (5) the selective σ1 R antagonist BD 1047 (3, 10, or 30 mg/kg, intraperitoneal (IP) injection). ETOH (1 g/kg) or saline was IP injected after 10 min. Then, ETOH-induced immobility was evaluated in an open field arena, ultrasonic vocalizations (USVs) indicating ethanol-induced emotional changes were recorded in a recording chamber, and the rats were sacrificed for the analysis of protein levels of σ1 R in several regions of the brain. RESULTS: Acute ethanol exposure increased the immobile time, 22-kHz USVs, and protein levels of σ1 R in the ventral tegmental area (VTA). However, pretreatment with acupuncture at HT7 induced recovery of immobile time, reduced 22-kHz USVs, and regulated the protein levels of σ1 R in the VTA. These effects have similarities with IP injection of BD 1047 (10 mg/kg). CONCLUSION: This study showed that acupuncture at HT7 regulates immobility and 22-kHz USVs via Sigma1 R in the VTA upon acute ETOH exposure.

Acupuncture alleviates chronic pain and comorbid conditions in a mouse model of neuropathic pain: the involvement of DNA methylation in the prefrontal cortex.

ABSTRACT: Chronic pain reduces life quality and is an important clinical problem associated with emotional and cognitive dysfunction. Epigenetic regulation of DNA methylation is involved in the induction of abnormal behaviors and pathological gene expression. We examined whether acupuncture can restore epigenetic changes caused by chronic pain, and identified the underlying mechanisms in neuropathic pain mice. Acupuncture treatment for 6 months (3 days/week) improved mechanical/cold allodynia and the emotional/cognitive dysfunction caused by left partial sciatic nerve ligation (PSNL)-induced neuropathic pain. The effects of acupuncture were associated with global DNA methylation recovery in the prefrontal cortex (PFC). Analysis of DNA methylation patterns in PFC indicated that 1364 overlapping genes among 4442 and 4416 methylated genes in the PSNL vs sham and PSNL vs acupuncture points groups, respectively, were highly associated with the DNA methylation process. Acupuncture restored the reduced expression of 5-methylcytosine, methyl-cytosine-phospho-guanine binding protein 2, and DNA methyltransferase family enzymes induced by PSNL in PFC. Methylation levels of Nr4a1 and Chkb associated with mitochondrial dysfunction were decreased in PFC of the PSNL mice, and increased by acupuncture. By contrast, high expression of Nr4a1 and Chkb mRNA in PSNL mice decreased after acupuncture. We also found that acupuncture inhibited the expression of Ras pathway-related genes such as Rasgrp1 and Rassf1. Finally, the expression of Nr4a1, Rasgrp1, Rassf1, and Chkb mRNA increased in the neuronal cells treated with Mecp2 small interfering RNA. These results suggest that acupuncture can relieve chronic pain-induced comorbid conditions by altering DNA methylation of Nr4a1, Rasgrp1, Rassf1, and Chkb in the PFC.

Quality of moxa wool contained in commercial moxibustion devices: test method and examples of waste particle concentration.

BACKGROUND: Moxibustion treatment involves a combination of thermal and chemical stimulation applied by the combustion of moxa wool. The quality of moxa wool is considered to be an important factor in moxibustion treatment traditionally and clinically. However, despite its importance, quantitative and objective methods for determining moxa wool quality are lacking. METHODS: Moxa wool and commercial indirect moxibustion (CIM) device specimens were randomly collected, dried and strained through sieves of various sizes for 10 h. After sieving, the residues remaining on each sieve were collected. The collected samples were weighed and microscopically observed. RESULTS: In this study, we observed that fibres mainly remained on sieves sized 425 µm, and particles were smaller than 300 µm. The residues between 425 and 300 µm varied between the products. In addition, moxa wool for direct moxibustion (DMW) exhibited significantly more fibres than moxa wool for indirect moxibustion (IMW). Most of the CIM devices using moxa wool had a quality similar to IMW, except for one CIM brand using moxa wool that contained three times more waste particles than IMW. CONCLUSION: Based on the results of this study, we conclude that the sieving method is useful for testing the quality of moxa wool even after the CIM manufacturing process. The sieve sizes of 425 and 300 µm could be used as a yardstick to determine the quality of moxa wool. Although this approach requires larger scale validation against existing standard methodologies, we believe it has great potential to be used to improve and safeguard the quality of moxa wool contained in commercial moxibustion devices.