Electroacupuncture attenuates inflammatory pain via peripheral cannabinoid receptor type 1 signaling pathway in mice.

Pain is strongly associated with neuro-immune activation. Thus, the emerging role of the endocannabinoid system in neuro-inflammation is important. Acupuncture has been used for over 2500 years and is widely accepted for the management of pain. Our study aimed to investigate the effects of electroacupuncture on the regulation of cannabinoid receptor type 1 within the peripheral nervous system. Inflammatory pain was induced by injecting Complete Freund's adjuvant to induce mechanical and thermal hyperalgesia. Electroacupuncture significantly attenuated the mechanical and thermal sensitivities, and AM251, a cannabinoid receptor type 1 antagonist, eliminated these effects. Dual immunofluorescence staining demonstrated that electroacupuncture elevated expression of cannabinoid receptor type 1, co-localized with Nav 1.8. Furthermore, electroacupuncture significantly reduced levels of Nav 1.8 and COX-2 by western blot analysis, but not vice versa as AM251 treatment. Our data indicate that electroacupuncture mediates antinociceptive effects through peripheral endocannabinoid system signaling pathway and provide evidence that electroacupuncture is beneficial for pain treatment.

Application of acupuncture in the emergency department for patients with ileus: A pilot prospective cohort clinical study.

Acupuncture can be conveniently used for pain control in patients with a variety of conditions, and it has obvious effects on various acute pains. In 2018, we implemented a program for emergency treatment with Chinese medicine to promote the integration of Chinese and Western medicine at the Emergency Department (ED). Ileus is a common cause of abdominal pain among patients in the ED, and it is an indication for emergency treatment with Chinese medicine. This study investigated the efficacy of acupuncture as a traditional Chinese medicine (TCM)-based treatment method for the treatment of patients with ileus in the ED. We analyzed data of patients with ileus, who visited ED between January and December 2019, and compared the length of ED stay between the Western medicine group and the Western medicine plus acupuncture group. Furthermore, pain intensity was measured by a visual analogue scale before and after acupuncture. We found that the length of ED stay was 10.8 hours lesser in the Western medicine plus acupuncture group than in the Western medicine group (P = .04), and the visual analogue scale score decreased by 2.0 on average from before to after acupuncture treatment (P = .02). Acupuncture treatment was effective and rapid in relieving the symptoms and discomfort in patients with ileus and in reducing their length of stay in the ED.

Mitochondrial Dysfunction as a Novel Target for Neuroprotective Nutraceuticals in Ocular Diseases.

The eyes require a rich oxygen and nutrient supply; hence, the high-energy demand of the visual system makes it sensitive to oxidative stress. Excessive free radicals result in mitochondrial dysfunction and lead to retinal neurodegeneration, as an early stage of retinal metabolic disorders. Retinal cells are vulnerable because of their coordinated interaction and intricate neural networks. Nutraceuticals are believed to target multiple pathways and have shown neuroprotective benefits by scavenging free radicals and promoting mitochondrial gene expression. Furthermore, encouraging results demonstrate that nutraceuticals improve the organization of retinal cells and visual functions. This review discusses the mitochondrial impairments of retinal cells and the mechanisms underlying the neuroprotective effects of nutraceuticals. However, some unsolved problems still exist between laboratory study and clinical therapy. Poor bioavailability and bioaccessibility strongly limit their development. A new delivery system and improved formulation may offer promise for health care applications.

Electroacupuncture attenuates chronic fibromyalgia pain through the phosphorylated phosphoinositide 3-kinase signaling pathway in the mouse brain.

OBJECTIVES: Fibromyalgia (FM) is a central nervous system disorder characterized by widespread mechanical hyperalgesia due to unknown mechanisms. Several inflammatory mediators, such as interleukin-1 (IL-1), IL-6, IL-8, and tumor necrosis factor, are increased in the serum of FM patients. Although medications including pregabalin, duloxetine, and milnacipran are used to treat FM, the results are unsatisfying. In the present study we assessed whether electroacupuncture (EA) can reduce chronic FM pain and then proposed an underlying mechanism for this effect. MATERIALS AND METHODS: Chronic FM pain was induced in mice by dual acid saline injection lasting up to 4 weeks. RESULTS: Chronic FM pain was treated by EA manipulation, but not in the sham operated group. Phosphorylated phosphatidylinositol 3-kinase (pPI3K), protein kinase B, mechanistic target of rapamycin, and nuclear factor kappa-light-chain-enhancer of activated B cells were unaltered in the mouse dorsal root ganglion (DRG) and spinal cord (SC) after inducing FM and administering EA treatment. The pPI3K-associated nociceptive signaling pathway was increased in the thalamus of FM mice, but reversed by EA. Similar results were observed in the mouse somatosensory cortex. CONCLUSION: These data suggest that EA has a significant effect on a signaling pathway in brain areas of FM mice. These findings suggest the value of EA for clinical practice.

Electroacupuncture Relieves CCI-Induced Neuropathic Pain Involving Excitatory and Inhibitory Neurotransmitters.

Neuropathic pain caused by peripheral tissue injuries to the higher brain regions still has no satisfactory therapy. Disruption of the balance of excitatory and inhibitory neurotransmitters is one of the underlying mechanisms that results in chronic neuropathic pain. Targeting neurotransmitters and related receptors may constitute a novel approach for treating neuropathic pain. We investigated the effects of electroacupuncture (EA) on chronic constriction injury- (CCI-) induced neuropathic pain. The mechanical allodynia and thermal hyperalgesia pain behaviors were relieved by 15 Hz EA but not by 2 and 50 Hz. These phenomena were associated with increasing γ-amino-butyric acid (GABA) receptors in the hippocampus and periaqueductal gray (PAG) but not N-methyl-D-aspartate receptors. Furthermore, excitatory neurotransmitter glutamate was decreased in the hippocampus and inhibitory neurotransmitter GABA was increased in the PAG under treatment with EA. These data provide novel evidence that EA modulates neurotransmitters and related receptors to reduce neuropathic pain in the higher brain regions. This suggests that EA may be a useful therapy option for treating neuropathic pain.

Targeting TRPV1 to relieve motion sickness symptoms in mice by electroacupuncture and gene deletion.

Motion sickness (MS) is an acute disorder that occurs in healthy individuals worldwide regardless of gender, age, or ethnicity. Our study used a mouse model to rule out the effects of any psychological factors related to MS and EA. Subjects were randomly separated into four groups, namely the control group (Con), motion sickness inducing group (MS), mentioning sickness inducing with electroacupuncture treatment group (EA) and motion sickness inducing only in TRPV1 knockout mice group (TRPV1-/-). The consumption of kaolin, a non-nutrient substance, was measured as a behavior observed response of an emetic reflex in a murine model. This behavior is referred to as pica behavior. Our results showed that pica behavior was observed in the MS group. Moreover, kaolin consumption in the EA group decreased to the average baseline of the control group. A similar result was observed in TRPV1 null mice. We also observed an increase of TRPV1 and related molecules in the thalamus, hypothalamic and brain stem after MS stimulation and a significant decrease in the EA and TRPV1 null groups. This is the first study to demonstrate that TRPV1 pathways are possibly associated with mechanisms of MS, and can be attended through EA or TRPV1 genetic manipulation.

Electroacupuncture Attenuates Induction of Inflammatory Pain by Regulating Opioid and Adenosine Pathways in Mice.

Although inflammatory pain is a common clinical condition, its mechanisms are still unclear. Electroacupuncture (EA), a well-known method of pain management, may reduce inflammatory pain by regulating neurons, astrocytes, and inflammatory signaling pathways. Injections of complete Freund's adjuvant (CFA), which can initiate cell-mediated inflammatory pain, resulted in significant hyperalgesia, which was subsequently prevented by EA. In CFA-injected mice, a dramatic increase was observed in the expression of the following proteins in the dorsal root ganglion and spinal cord dorsal horn: the astrocytic marker GFAP, S100B, RAGE, pPKCε, COX-2, pERK, and pNFκB. These effects were reversed by EA. In addition, mechanical hyperalgesia was significantly reduced in the N6-cyclopentyladenosine (CPA) i.p. or i.m. and endomorphin (EM) i.p. groups. Neither EM i.m. nor EM i.p. exhibited any analgesic effect on thermal hyperalgesia. However, both CPA i.m. and CPA i.p. attenuated thermal hyperalgesia in the mouse inflammatory pain model. We showed that CPA reduced COX-2 and pPKCε expression. However, EM administration did not reduce COX-2 levels. Combined administration of naloxone and rolofylline increased pPKCε and COX-2 pathways. Taken together, our study results revealed a novel and detailed mechanism of EA-induced analgesia that involves the regulation of the opioid and adenosine pathways.

Electroacupuncture Attenuates CFA-induced Inflammatory Pain by suppressing Nav1.8 through S100B, TRPV1, Opioid, and Adenosine Pathways in Mice.

Pain is associated with several conditions, such as inflammation, that result from altered peripheral nerve properties. Electroacupuncture (EA) is a common Chinese clinical medical technology used for pain management. Using an inflammatory pain mouse model, we investigated the effects of EA on the regulation of neurons, microglia, and related molecules. Complete Freund's adjuvant (CFA) injections produced a significant mechanical and thermal hyperalgesia that was reversed by EA or a transient receptor potential V1 (TRPV1) gene deletion. The expression of the astrocytic marker glial fibrillary acidic protein (GFAP), the microglial marker Iba-1, S100B, receptor for advanced glycation end-products (RAGE), TRPV1, and other related molecules was dramatically increased in the dorsal root ganglion (DRG) and spinal cord dorsal horn (SCDH) of CFA-treated mice. This effect was reversed by EA and TRPV1 gene deletion. In addition, endomorphin (EM) and N6-cyclopentyladenosine (CPA) administration reliably reduced mechanical and thermal hyperalgesia, thereby suggesting the involvement of opioid and adenosine receptors. Furthermore, blocking of opioid and adenosine A1 receptors reversed the analgesic effects of EA. Our study illustrates the substantial therapeutic effects of EA against inflammatory pain and provides a novel and detailed mechanism underlying EA-mediated analgesia via neuronal and non-neuronal pathways.

[Soluble nitrogen and soluble phosphorus dynamics during foliar litter decomposition in winter in alinine forest streams].

In order to understand the dynamic pattern of soluble nitrogen and soluble phosphorus in the headwater streams during the process of litter decomposition in winter, a field experiment using litterbag method was conducted in an alpine forest in Western Sichuan, China. The foliar litter of two dominant canopy trees (Sabina saltuaria, and Larix mastersiana) and two shrubs (Salix paraplesia and Rhododendron lapponicum) were selected. The litterbags were placed in a headwater stream, river, riparian zone and closed canopy, and sampled in different freezing-thawing periods of winter (pre-freezing period, freezing period and thawing period). The results indicated that the soluble nitrogen content of foliar litter showed little changes over a whole winter decomposition regardless of species. In contrast, the soluble phosphorus content displayed the order as river < stream < riparian zone < closed canopy, and showed a decrease tendency in stream, river and riparian, although little changes under closed canopy over a whole winter decomposition. Correlation analysis suggested that the dynamics of soluble phosphorus content significantly correlated to the average temperature, positive accumulated temperature, negative accumulated temperature and flow velocity during the decomposition in winter. The dynamics of soluble nitrogen content only exhibited significant correlations with positive accumulated temperature. Additionally, litter quality (species) also controlled the dynamics of soluble nitrogen and soluble phosphorus content as litter decomposition proceeded. The results implied that soluble phosphorus could be more liable to loss in streams and rivers during litter decomposition compared with soluble nitrogen, which could further provide some new ideas in understanding nitrogen and phosphorus cycling in this alpine forest.

Electroacupuncture Reduces Carrageenan- and CFA-Induced Inflammatory Pain Accompanied by Changing the Expression of Nav1.7 and Nav1.8, rather than Nav1.9, in Mice Dorsal Root Ganglia.

Several voltage-gated sodium channels (Navs) from nociceptive nerve fibers have been identified as important effectors in pain signaling. The objective of this study is to investigate the electroacupuncture (EA) analgesia mechanism by changing the expression of Navs in mice dorsal root ganglia (DRG). We injected carrageenan and complete Freund's adjuvant (CFA) into the mice plantar surface of the hind paw to induce inflammation and examined the antinociception effect of EA at the Zusanli (ST36) acupoint at 2 Hz low frequency. Mechanical hyperalgesia was evaluated by using electronic von Frey filaments, and thermal hyperalgesia was assessed using Hargreaves' test. Furthermore, we observed the expression and quality of Navs in DRG neurons. Our results showed that EA reduced mechanical and thermal pain in inflammatory animal model. The expression of Nav1.7 and Nav1.8 was increased after 4 days of carrageenan- and CFA-elicited inflammatory pain and further attenuated by 2 Hz EA stimulation. The attenuation cannot be observed in Nav1.9 sodium channels. We demonstrated that EA at Zusanli (ST36) acupoint at 2 Hz low-frequency stimulation attenuated inflammatory pain accompanied by decreasing the expression of Nav1.7 and 1.8, rather than Nav1.9, sodium channels in peripheral DRG neurons.

Acid-sensing ion channel 3 mediates peripheral anti-hyperalgesia effects of acupuncture in mice inflammatory pain.

BACKGROUND: Peripheral tissue inflammation initiates hyperalgesia accompanied by tissue acidosis, nociceptor activation, and inflammation mediators. Recent studies have suggested a significantly increased expression of acid-sensing ion channel 3 (ASIC3) in both carrageenan- and complete Freund's adjuvant (CFA)-induced inflammation. This study tested the hypothesis that acupuncture is curative for mechanical hyperalgesia induced by peripheral inflammation. METHODS: Here we used mechanical stimuli to assess behavioral responses in paw and muscle inflammation induced by carrageenan or CFA. We also used immunohistochemistry staining and western blot methodology to evaluate the expression of ASIC3 in dorsal root ganglion (DRG) neurons. RESULTS: In comparison with the control, the inflammation group showed significant mechanical hyperalgesia with both intraplantar carrageenan and CFA-induced inflammation. Interestingly, both carrageenan- and CFA-induced hyperalgesia were accompanied by ASIC3 up-regulation in DRG neurons. Furthermore, electroacupuncture (EA) at the ST36 rescued mechanical hyperalgesia through down-regulation of ASIC3 overexpression in both carrageenan- and CFA-induced inflammation. CONCLUSIONS: In addition, electrical stimulation at the ST36 acupoint can relieve mechanical hyperalgesia by attenuating ASIC3 overexpression.

[Screening and identification of steroidal saponins-producing endophytes from Paris polyphylla var. chinensis Franch].

Two endophytic strains SS01 and SS02 with the potential for producing steroidal saponins were isolated from the underground stems of Paris polyphylla var. chinensis Franch. The TLC comparison indicated that there are 3 sports with similar R(f) between the metabolites of SS01 and the saponins of Paris polyphylla var. chinensis Franch. And there are 2 sports with similar R(f) between the metabolites of SS02 and the saponins of Paris polyphylla var. chinensis The and that biochemical SS01 Franch. characteristics of morphology, physiological belonged showed to Enterobacteriaceae and SS02 belonged to Bacillus sp.. The 16S rDNA of SS01 and SS02 were PCR and sequenced. The accessions of GenBank are AY842143 and AY842144, respectively. The two 16S rDNA phylogenetic trees were constructed by comparing with the published 16S rDNA sequences of the relative bacteria species. In the first phylogenetic tree SS01 and Cedecea davisae DSM 4568 was the closest relative with 98.9% sequence similarity, and in the second phylogenetic tree SS02 and Paenibacillus daejeonensis was the closest relative with 97.7% sequence similarity. According to the phylogenetic analysis they were identified as Cedecea davisae SS01 and Paenibacillus daejeonensis SS02, respectively.