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BACKGROUND: The efficacy of acupuncture at Zusanli (ST36) in alleviating lower-limb pain is widely acknowledged in clinical practice, while its underlying mechanism remains incompletely elucidated. Our previous research had revealed that the prompt analgesia induced by needling-ST36 was accompanied by expression alterations in certain exco-nucleotidases within the sciatic nerve. Building upon this finding, the current work focused on NTPDase1, the primary ecto-nucleotidase in the human body, which converts ATP into AMP. METHODS: A 20-min acupuncture was administered unilaterally at the ST36 on rats with acute ankle arthritis. The pain thresholds of the injured hind paws were determined. Pharmacological interference was carried out by introducing the corresponding reagents to the sciatic nerve. ATP levels around the excised nerve were measured using a luciferase-luciferin assay. Live calcium imaging, utilizing the Fura 2-related-F340/F380 ratio, was conducted on Schwann cells in excised nerves and cultured rat SCs line, RSC96 cells. RESULTS: The analgesic effect induced by needling-ST36 was impaired when preventing ATP degradation via inhibiting NTPDase1 activities with ARL67156 or Ticlopidine. Conversely, increasing NTPDase1 activities with Apyrase duplicated the acupuncture effect. Similarly, preventing the conversion of AMP to adenosine via suppression of NT5E with AMP-CP hindered the acupuncture effect. Unexpectedly, impeded ATP hydrolysis ability and diminished NTPDase1 expression were observed in the treated group. Agonism at P2Y2Rs with ATP, UTP, or INS365 resulted in anti-nociception. Contrarily, antagonism at P2Y2Rs with Suramin or AR-C 118925xx prevented acupuncture analgesia. Immunofluorescent labeling demonstrated that the treated rats expressed more P2Y2Rs that were predominant in Schwann cells. Suppression of Schwann cells by inhibiting ErbB receptors also prevented acupuncture analgesia. Finally, living imaging on the excised nerves or RSC96 cells showed that agonism at P2Y2Rs indeed led to [Ca2+]i rise. CONCLUSION: These findings strongly suggest that the analgesic mechanism of needling-ST36 on the hypersensation in the lower limb partially relies on NTPDase1 activities in the sciatic nerve. In addition to facilitating adenosine signaling in conjunction with NT5E, most importantly, NTPDase1 may provide an appropriate low-level ATP milieu for the activation of P2Y2R in the sciatic nerve, particularly in Schwann cells.
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Analgesia por Acupuntura , Terapia por Acupuntura , Antígenos CD , Artrite , Ratos , Humanos , Animais , Apirase , Tornozelo , Dor , Nervo Isquiático/metabolismo , Trifosfato de Adenosina/metabolismo , Analgésicos , Monofosfato de Adenosina , Adenosina , Pontos de AcupunturaRESUMO
BACKGROUND: The activation of subcutaneous mast cells (MCs) helps to trigger the analgesic effect induced by acupuncture (AP), a traditional oriental therapy, that has been gradually accepted worldwide. This work aimed to reveal whether the serotonin (5-hydroxytryptamine, 5-HT) released from MCs plays an important role in this process, which has a controversial effect in the mechanism of pain. METHODS: In vivo tests, a 20-min session of AP was applied at Zusanli acupuncture point (acupoint) of acute ankle arthritis rats. Pain thresholds of the injured hindpaw were assessed to reflect the pain state, and the targeting substances in the interstitial space of the treated acupoint were sampled by microdialysis. In vitro experiments, exogenous 5-HT (exo-5-HT) was introduced to mediate adenosine triphosphate (ATP) release from cultured MCs. RESULTS: Needling promoted 5-HT accumulation at the Zusanli acupoint, which was prevented by sodium cromolyn. AP's analgesic effect was suppressed by the inhibition of 5-HT receptors at the acupoint, especially 5-HT1A subtype. In vitro tests, mechanical perturbation mimicking needling stimulation induced MCs to release 5-HT. 1 µM and 10 µM of exo-5-HT facilitated ATP release, which was restrained by blocking of 5-HT1 receptors rather than 5-HT3 receptors. As 5-HT, ATP and adenosine were also transiently accumulated in the treated acupoint during needling. Promoting ATP hydrolysis or activation adenosine A1 receptors duplicated AP analgesic effect. Finally, the inhibition of ATP receptors by suramin or pyridoxal phosphate-6-azo tetrasodium salt hydrate (PPADS) prevented AP analgesic effect. CONCLUSIONS: Our results suggest that MC-associated 5-HT release at acupoints contributes to AP analgesia, and the mediation of ATP secretion through 5-HT1A receptors might be the underlying mechanism at play. ATP could facilitate adenosine production or the propagation of needling signals.
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Analgesia por Acupuntura , Artrite , Doença de Hashimoto , Animais , Ratos , Trifosfato de Adenosina , Serotonina , Pontos de Acupuntura , Mastócitos , Adenosina , AnalgésicosRESUMO
Our and in vitro studies had confirmed that mechanosensitive ATP release and accumulation in acupoints was elicited by acupuncture (AP), which might be a pivotal step for triggering AP analgesia. But to date, the dynamics of extracellular ATP (eATP) in the interstitial space during AP process was poorly known, mainly due to the low temporal resolution of the current detection approach. This study attempted to capture rapid eATP signals in vivo in the process of needling, and further explored the role of this eATP mobilization in initiating AP analgesic effect. Ipsilateral 20-min needling was applied on Zusanli acupoint (ST36) of complete Freund's adjuvant (CFA)-induced ankle arthritis rats. Pain thresholds were assessed in injured-side hindpaws. eATP in the interstitial space was microdialyzed and real-time quantified by luciferin-luciferase assay at 1-min interval with the aid of the microfluid chip. We revealed in behavioral tests that modulation of eATP levels in ST36 influenced AP analgesic effect on ankle arthritis. A transient eATP accumulation was induced by needling that started to mobilize at 4 min, climbed to the peak of 11.21 nM within 3.25 min and gradually recovered. Such AP-induced eATP mobilization was significantly impacted by ankle inflammation, needling depth, needle manipulation, and the presence of local ecto-nucleotidases. This work reveals that needling elicits a transient eATP mobilization in acupoints, which contributes to initiating AP analgesia. This study will help us better understand the peripheral mechanism of AP analgesia and guide clinicians to optimize the needle manipulations to improve AP efficacy.
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Analgesia por Acupuntura , Terapia por Acupuntura , Artrite , Ratos , Animais , Pontos de Acupuntura , Analgésicos , Trifosfato de AdenosinaRESUMO
INTRODUCTION: Knee osteoarthritis (KOA) is a chronic inflammatory disease with high morbidity and disability. As the aging and obese population increase, so will the medical services for this disease. The purpose of this study is to compare the clinical efficacy of herbal activated carbon smokeless moxibustion and traditional moxibustion in the treatment of KOA and to determine the clinical efficacy of herbal activated carbon smokeless moxibustion in the treatment of KOA. METHODS/DESIGN: This is a multicenter, two parallel-group, single-blind, randomized controlled trial. Eighty-eight subjects with KOA (Kellgren Lawrence grade II or III) will be recruited and randomly treated with smokeless moxibustion or traditional moxibustion in the ratio of 1:1. The smokeless moxibustion group will use plant herbal activated carbon smokeless moxa cone. The traditional moxibustion group will be treated with pure moxa cone. Subjects in both groups will receive treatment at the affected knee(s) at the acupuncture point ST35, EX-LE2, and EX-LE4. Subjects in both groups will receive 3 sessions per week of moxibustion for 4 weeks. The primary outcome are changes in the Western Ontario and McMaster Universities Osteoarthritis Index pain scores from baseline to week 24. Secondary outcomes include visual analog scale, 50 yards fast walking time, short-form heath survey 36, overall clinical efficacy evaluation, self-assessment of safety, treatment credibility and expectancy, and cytokines related to osteoarthritis in serum. DISCUSSION: This randomized single-blind controlled trial takes traditional moxibustion as the control group to provide strict evidence for the clinical efficacy and safety of herbal activated carbon smokeless moxibustion in the treatment of KOA.
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Moxibustão , Osteoartrite do Joelho , Carvão Vegetal , Citocinas , Humanos , Lobelina , Moxibustão/métodos , Estudos Multicêntricos como Assunto , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego , Resultado do TratamentoRESUMO
This review summarizes experimental evidence indicating that subcutaneous mast cells are involved in the trigger mechanism of analgesia induced by acupuncture, a traditional oriental therapy, which has gradually become accepted worldwide. The results are essentially based on work from our laboratories. Skin mast cells are present at a high density in acupuncture points where fine needles are inserted and manipulated during acupuncture intervention. Mast cells are sensitive to mechanical stimulation because they express multiple types of mechanosensitive channels, including TRPV1, TRPV2, TRPV4, receptors and chloride channels. Acupuncture manipulation generates force and torque that indirectly activate the mast cells via the collagen network. Subsequently, various mediators, for example, histamine, serotonin, adenosine triphosphate and adenosine, are released from activated mast cells to the interstitial space; they or their downstream products activate the corresponding receptors situated at local nerve terminals of sensory neurons in peripheral ganglia. The analgesic effects are thought to be generated via the reduced electrical activities of the primary sensory neurons. Alternatively, these neurons project such signals to pain-relevant regions in spinal cord and/or higher centers of the brain.
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Pontos de Acupuntura , Analgesia , Humanos , Mastócitos , Dor , Células Receptoras SensoriaisRESUMO
Acupuncture is a medical modality based on the theory of traditional Chinese medicine, and its effect is relatively dependent on acupoint specificity. However, there is little knowledge on acupoint specificity versus acupuncture outcomes because of the deficiency of rigorous investigation on this topic, which has impeded the growing legitimacy of acupuncture in the mainstream of medicine as an evidence-based therapy. Therefore, it is of utmost importance to clarify this critical issue. The present study aims to verify the phenomenon of acupoint specificity in acupuncture-induced cardiovascular regulation and explore the biological mechanism by measuring mast cells' degranulation and adenosine release. This study was conducted to explore the specificity of acupoints in an acute bradycardia rabbit model. After electroacupuncture (EA) stimulation at PC6, PC control (con) 1, PC con 2, LU7, LI11, and nonacupoint, only the PC6 group showed a significant improvement in relative heart rate as compared to that of the model group. There was no significant difference between the relative heart rate of other EA groups and that of the model group. Historical results also showed that the ratio of degranulated mast cells in PC6 was significantly higher than other acupoints and control points. From the results of high-performance liquid chromatography (HPLC), a transient elevation of adenosine concentration during EA was only observed on acupoints and control points (P < 0.05) along the pericardium meridian. The EA-induced adjustment on acute bradycardia exhibits a relative specificity of acupoints, which may be related to mast cell degranulation and adenosine release in local acupoint areas. Increased degranulation of mast cells and augmentation of adenosine release during EA may be the mechanisms for PC6 having significantly better acupuncture effects than other acupoints and nonacupoints.
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This paper introduces a new technique combining microdialysis with patch clamp to detect the changes in ATP (adenosine triphosphate) concentration in acupoints during acupuncture. The microdialysis probe was implanted into the Zusanli acupoint (ST 36) of adult SD (Sprague Dawley) rats to sample acupoint fluid containing ATP released during acupuncture. Then, the fluid with ATP was delivered in real time to 293 T cells overexpressing P2X3 receptors, with which we could carry out patch clamp experiments. The results showed that changes in membrane currents could reflect changes in the concentration of ATP. Thus, we can successfully detect ATP released in acupoints during acupuncture in real time. This technique provides us with a new way to study the mechanism of acupuncture signal initiation.
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Focusing on the mechanical effect of traditional Chinese acupuncture, this study builds a mathematical model that simulates the mechanical process of lifting-thrusting needle. Analytic and numerical solutions are obtained to explore the mechanical information (displacement, strain, stress, and energy) in the skin tissue. Our results show that (1) needle manipulation leads to tissue displacement and mechanical stress field, but the needle should be inserted into the right position (about π/ω cm around the acupoint, where ω is the angular frequency) and enough depth (about 2 cm in lower limbs) to achieve effective mechanical stimuli; (2) the tissue displacement decays with an increase of distance from the stimulus position, more rapidly at higher frequencies; (3) there is an inverse relationship between the area of the 'effective influence region' (where shear strain > 0.2) and the stimulus frequency, which means larger needle movement is needed at higher frequencies to achieve a better curative effect; (4) more energy is required to maintain high frequency manipulation. This study proposes a preliminary comprehension of the mechanical response around the needle during the acupuncture process.
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OBJECTIVE: To observe the effect of herb-partitioned moxibustion at the Tianshu (ST 25) and Qihai (CV 6) acupoints in rats with Crohn's disease, and explore the underlying mechanism from dopamine (DA) and dopamine receptor 1 (D1R) in the colon, spinal dorsal horn and hypothalamus. METHODS: The rats were randomly divided into the normal, model (CD), herb-partitioned moxibustion (Mox) and mesalazine (Mesa) groups. Damage in the colons was scored and observed by hematoxylin and eosin staining. DA and D1R protein expression in the colonic mucosa were detected by immunohistochemistry. The concentrations of DA and D1R in the spinal dorsal horn and hypothalamus were measured by enzyme-linked immunosorbent assay, and D1R mRNA expression was evaluated by quantitative real-time polymerase chain reaction. RESULTS: In the colon, compared with the normal group, DA, D1R protein expressions and D1R mRNA expression were significantly higher in the model group, while decreased in the Mox group and the Mesa group. In the spinal dorsal horn and hypothalamus, compared with the normal group, the concentrations of DA and D1R, and the D1R mRNA expressions were significantly higher in the model group, and decreased in the Mox group and the Mesa group. CONCLUSION: Herb-partitioned moxibustion at the Tianshu (ST 25) and Qihai (CV 6) acupoints relieved ulceration in CD rats, the underlying mechanism maybe relative with the regulation of DA and D1R in the colon, spinal dorsal horn and hypothalamus by moxibustion.
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Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Doença de Crohn/tratamento farmacológico , Doença de Crohn/terapia , Dopamina/metabolismo , Moxibustão/métodos , Receptores Dopaminérgicos/metabolismo , Animais , Doença de Crohn/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Masculino , Mesalamina/uso terapêutico , Distribuição Aleatória , Ratos , Reação em Cadeia da Polimerase em Tempo RealRESUMO
OBJECTIVE: The present study aimed at observing the profile of metabolites in sensitized acupoints induced by myocardial ischemia (MI) and the effect of acupuncture intervention on the changes of the metabolites so as to explore the material basis of acupoint sensitization. METHODS: A total of 20 New Zealand rabbits were randomly and equally divided into a control group and a model group. The MI model was established by occlusion of the anterior descending branch of the left coronary artery with a controllable air balloon inflation method for 5 min/time, twice a day (4-hours' interval) for continuous 5 days (the first stage of MI). After one day's rest, another 5 days' occlusion was conducted again (the second stage of MI) in the same way. The rabbits of the control group were treated with the same procedures but without occlusion. Subcutaneous microdialysis fluid samples were collected from "Neiguan" (PC 6), "Shenmen" (HT 7), "Xinshu" (BL 15), and "Taixi" (KI 3) regions on day 8(after recovery from operation), 14 (the first stage of MI), and 20 (the second stage of MI), as well as collected from PC 6 region during and post-acupuncture stimulation of PC 6, respectively. Manual acupuncture stimulation was applied to the right PC 6 for 30 min. Partial least squares -linear discriminant analysis (PLS-DA) was used to identify different metabolism patterns of the microdialysis fluid sample between groups and at different time-points in the same one group, and the distinct metabolites as the potential markers between groups were weighted via the values of variable importance in the projection (VIP) in combination with t-test analysis. An area under the curve (AUC) >1.0 indicated a test exhibiting good discrimination between groups. RESULTS: Six metabolites identified to be significantly different between the control and model groups were L-glutamic acid, phenylalanine and 3-hydroxyisobutyric acid (which were significantly increased relevant to the control group), and L-histidine, octadecanedioic acid and 9-keto palmitic acid (significantly decreased relevant to the control group) in the microdialysate of PC 6, HT 7 and BL 15 regions. In the microdialysate of PC 6, 4 metabolites including L-glutamic acid, octadecanedioic acid and 8-isohydroxy PGF 2 α (significantly increased), as well as L-histidine (markedly decreased) were identified to be considerably different between the model and control groups. After acupuncture for 30 min, the AUC level of L-glutamic acid was further significantly increased (P<0.05), that of L-histidine obviously decreased, and those of octadecanedioic acid and 8-isohydroxy PGF 2 α turned back nearly to the level of pre-MI. CONCLUSION: L-glutamic acid, phenylalanine, 3-hydroxyisobutyric acid, L-histidine, octadecanedioic acid and 9-keto palmitic acid from PC 6, HT 7 and BL 15 regions may be used as the material biomarker for MI-induced sensitization of these acupoints. Manual acupuncture intervention of PC 6 induces a significant change of L-histidine and L-glutamic acid in the local subcutaneous tissues.
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Eletroacupuntura , Isquemia Miocárdica , Pontos de Acupuntura , Animais , Coelhos , Tela SubcutâneaRESUMO
The distribution and location of mast cells are closely related to their physiological and pathological functions, such as allergic responses, immunity, and fibrosis, and are used in acupuncture. In this study, the distribution of mast cells in vivo was observed, and mechanical clues for understanding their distribution based on mechanical niches were explored. By toluidine blue staining and immunohistochemical staining, we examined the distribution and location of mast cells in rat skin and found that mast cells are distributed in a spatially nonuniform manner, preferring to locate at regions in the tissue and extracellular matrix with stiffness changes. In vitro experiments for studying the distribution of rat basophilic leukemia (RBL-2H3) mast cell line on poly-di-methyl-siloxane (PDMS) substrates with stiffness variations were performed. It was found that RBL-2H3 cells migrate and tend to remain in the areas with stiffness variations. The present research suggests that changing the stiffness of local tissues may stimulate mast cell recruitment, which may be the method by which some traditional Chinese medicine treatments, such as acupuncture. On the basis of the origin of mast cells and our experimental results, we predict that mast cells exist in tissues that contain permeable capillaries and prefer regions with stiffness changes. We discussed this prediction using examples of specific tissues from some cases.
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Mastócitos/metabolismo , Acupuntura , Animais , Linhagem Celular Tumoral , Dimetilpolisiloxanos , Fibrose/metabolismo , Mastócitos/fisiologia , Nylons , Ratos , Pele/citologiaRESUMO
Nerve and mast cells are densely distributed around acupoints in connective tissue. To explore the internal relations between them in acupuncture effect, we examined dorsal root potential (DRP) response to acupuncture at Zusanli (ST36) under sodium cromoglicate (DSCG, a mast cell stabilizer) intervention in anesthetized Sprague-Dawley (SD) rats. We used single unit nerve recording techniques to collect nerve signals from DRP afferent nerves for a 45-minute period that includes 4 stages, that is, base, drug absorption, acupuncture, and recovery stages. We analyzed the recorded signals from time-domain and frequency-domain perspectives. The results showed that once acupuncture needle was inserted, twisting needle excited more nerves discharges than those at base discharges in ACU (from 35.1 ± 7.2 to 47 ± 9.2 Hz, P = 0.004), and there existed the same trend in Saline + ACU group (from 23.8 ± 2.6 to 29.8 ± 4.2 Hz, P = 0.059). There was no change of nerve discharges under twisting needle with injection of DSCG (from 34.8 ± 5.3 to 34.7 ± 4.4 Hz, P = 0.480). We conclude that acupuncture manipulation promotes neural signal production and DSCG could partly inhibit nerve discharges.
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Acupuncture is one of the most promising modalities in complimentary medicine. However, the underlying mechanisms are not well understood yet. We found that in TRPV2 knockout male mice, acupuncture-induced analgesia was suppressed with a decreased activation of mast cells in the acupoints stimulated. The mast cell stabilizer sodium cromolyn could suppress the release of adenosine in the acupoints on male rats. A direct injection of adenosine A1 receptor agonist or histamine H1 receptor agonist increased ß-endorphin in the cerebral-spinal fluid in the acute adjuvant arthritis male rats and thus replicated the analgesic effect of acupuncture. These observations suggest that the mast cell is the central structure of acupoints and is activated by acupuncture through TRPV2 channels. The mast cell transduces the mechanical stimuli to acupuncture signal by activating either H1 or A1 receptors, therefore triggering the acupuncture effect in the subject. These findings might open new frontiers for acupuncture research.
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Canais de Cálcio/metabolismo , Histamina/metabolismo , Receptor A1 de Adenosina/metabolismo , Canais de Cátion TRPV/metabolismo , Acupuntura/métodos , Analgesia por Acupuntura/métodos , Pontos de Acupuntura , Terapia por Acupuntura/métodos , Adenosina/metabolismo , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Cromolina Sódica/metabolismo , Agonistas dos Receptores Histamínicos/farmacologia , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ratos , Ratos Sprague-Dawley , beta-Endorfina/metabolismoRESUMO
OBJECTIVE: To develop an animal model suitable for the study of acupoint sensitization in myocardial ischemia(MI) animals by observing changes of the mechanical withdrawal threshold (pain threshold, PT). METHODS: Twenty New Zea-land rabbits were randomly divided into control and model groups (n=10 in each group). The controllable MI model was set up by installing a balloon occluder at the left anterior descending branch of the left coronary artery. Air inflation of the balloon was given for 5 min/time, twice a day (4-hours' interval) for continuous 5 days (the first stage of MI), with one day's rest, then, another 5 days' air inflation was conducted again (2nd stage of MI). Electrocardiogram (ECG) of the standard limb lead â ¡ was recorded for assessing MI, and myocardial 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to verify the degree of ischemic myocardium. The PT of the skin areas of "Neiguan" (PC 6), "Shenmen" (HT 7),"Taixi"(KI 3),hind paw(HP)was detected under conscious conditions,before MI, on day 8(after recovery from MI), day 14 (the first stage of MI), and day 20 (the second stage of MI), respectively. RESULTS: The controllable MI model was successful due to a marked elevation of ECG ST â ¡ after inflation of the implanted balloon and a distinct recovery after balloon deflation (P<0.05). The myocardial TTC staining showed that the area of the myocardial necrosis was about 10%. The PT values were significantly decreased in PC 6 area at the first stage of MI and in both PC 6 and HT 7 regions at the 2nd stage of MI (P<0.01), suggesting a close relationship between the acupoints of the Pericardium and Heart meridians and the heart in terms of the basic theory of Chinese medicine. CONCLUSIONS: MI may induce a reduction of PT of some related acupoints in MI rabbits, and the controllable MI model of the present study is helpful to the study of acupoint sensitization phenomenon after occurrence of visceral diseases.
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Pontos de Acupuntura , Meridianos , Isquemia Miocárdica/terapia , Animais , Modelos Animais de Doenças , Eletroacupuntura , Humanos , Miocárdio , CoelhosRESUMO
This research was conducted to verify the structural and functional characteristics of mast cells in the electroacupuncture (EA) effects on bradycardia. First, we examined the mast cell density at PC 6, adjacent acupoint LU 7, and a non-acupoint. We tested the effects of EA at PC 6 on heart rate (HR) and blood pressure (BP) in rabbits with pituitrin-induced bradycardia. We also injected sodium cromolyn (Cro), a mast cell membrane stabilizer, at PC 6 30 min before EA to investigate if it affected the EA effects. The results showed that in both PC 6 and LU 7, the mast cell densities were higher than in the non-acupoint (P < 0.05). EA could induce mast cell degranulation at PC 6, which could be suppressed by sodium cromolyn (P < 0.05). EA improved HR, though the change was relatively small in the initial stage with a significant change at 35 min after modelling (P < 0.05). BP significantly improved at 10 min after the onset of pituitrin-induced bradycardia (P < 0.05). The EA effects on both HR and BP were suppressed by sodium cromolyn (P < 0.05). Therefore, we concluded that mast cells in the acupoint are important for the EA effects against pituitrin-induced bradycardia in rabbits.
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Pontos de Acupuntura , Bradicardia/etiologia , Bradicardia/fisiopatologia , Degranulação Celular/imunologia , Mastócitos/imunologia , Hormônios Neuro-Hipofisários/efeitos adversos , Animais , Pressão Sanguínea , Bradicardia/diagnóstico , Bradicardia/terapia , Contagem de Células , Modelos Animais de Doenças , Eletroacupuntura , Eletrocardiografia , Frequência Cardíaca , Masculino , Mastócitos/metabolismo , Mastócitos/patologia , CoelhosRESUMO
Acupoints (Xuewei) are the focus of acupuncture on the body in traditional Chinese medicine treatment. Mast and nerve cells share a perivascular location and are abundantly found at these acupoints. Both environmental factors and medical treatments (chemical and physical stimuli) can stimulate local mast cells (MCs) to degranulate and thus release histamine which then activates the nearby nerves and therefore contributes to a signal transmission from the peripheral to the central nervous system. In this paper, a mathematical model is constructed to describe the signaling pathways that originate from the cells located at an acupoint. We show that: (1) peripheral stimuli induce the release of histamine from MCs; (2) histamine excites receptors in primary sensory neurons and leads to membrane action potentials; (3) histamine released from MCs at an acupoint plays a key role in response to acupuncture. These results are consistent with experimental observations. Furthermore, this study may facilitate our understanding of the signal transmission process that occurs in response to peripheral stimuli as well as provide a useful modeling tool for quantitatively analyzing immune and acupuncture mechanisms that involve MCs.
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Terapia por Acupuntura , Histamina/farmacologia , Modelos Neurológicos , Neurônios/fisiologia , Pontos de Acupuntura , Animais , Simulação por Computador , Fluorescência , Humanos , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Neurônios/efeitos dos fármacos , Células Receptoras Sensoriais/efeitos dos fármacos , Células Receptoras Sensoriais/fisiologiaRESUMO
OBJECTIVE: To investigate the effects of warming moxibustion Tianshu (ST 25, bilateral) and Qihai (CV 6) in patients with diarrhea-dominant irritable bowel syndrome (D-IBS) by assessing predominant factors, and determining the best factor combinations and their interactions. To identify the optimal quantity of warming moxibustion Tianshu (ST 25, bilateral) and Qihai (CV 6) to achieve optimal efficacy. METHODS: An L9 (34) orthogonal design was applied to 233 confirmed subjects based on the three most influential factors and the three most frequently used levels. Nine programs were designed. Subjects were assigned to four subgroups according to age and gender; each subject underwent one of the nine programs randomly. We selected Tianshu (ST 25, bilateral) and Qihai (CV 6). The scores of symptoms and the IBS Quality of Life (IBS-QOL) were evaluated after the final treatment. RESULTS: After treatment, clinical symptoms of all patients were significantly improved (P = 0.001). Quality of life also improved significantly (P < 0.05). For all the participants, frequency was the dominating factor regarding symptoms (P = 0.01). Duration was the dominating factor for quality of life (P = 0.0001). The best combination for improving symptoms in 30-40-year-old male and female patients was two courses of 10 min each once a day, and for 41-50-year-old male and female patients it was three courses of 10 min (males) or 30 min (females) twice a day. The best combination for quality of life was three courses of 20 min once a day. No interaction was found between frequency and course, or frequency and duration. CONCLUSION: Warming moxibustion Tianshu (ST 25, bilateral) and Qihai (CV 6) is a promising therapy for D-IBS. To acquire optimal efficacy, the three main factors (duration, frequency and treatment course) of the warming moxibustion should reach a specific quantity and be combined appropriately.
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Perinatal hypoxic-ischemic (HI) brain injury results in death or profound long-term neurologic disability in both children and adults. However, there is no effective pharmacological therapy due to a poor understanding of HI events, especially the initial triggers for hypoxic-ischemic injury such as disrupted ionic homeostasis and the lack of effective intervention strategy. In the present study, we showed that neonatal brains undergo a developmental increase in the disruption of K+ homeostasis during simulated ischemia, oxygen-glucose deprivation (OGD) and neonatal HI cortex has a triple phasic response (earlier attenuation, later enhancement, and then recovery) of disrupted K+ homeostasis to OGD. This response partially involves the activity of the δ-opioid receptor (DOR) since the earlier attenuation of ischemic disruption of K+ homeostasis could be blocked by DOR antagonism, while the later enhancement was reversed by DOR activation. Similar to DOR activation, acupuncture, a strategy to promote DOR activity, could partially reverse the later enhanced ischemic disruption of K+ homeostasis in the neonatal cortex. Since maintaining cellular K+ homeostasis and inhibiting excessive K+ fluxes in the early phase of hypoxic-ischemic insults may be of therapeutic benefit in the treatment of ischemic brain injury and related neurodegenerative conditions, and since many neurons and other cells can be rescued during the "window of opportunity" after HI insults, our first findings regarding the role of acupuncture and DOR in attenuating ischemic disruption of K+ homeostasis in the neonatal HI brain suggest a potential intervention therapy in the treatment of neonatal brain injury, especially hypoxic-ischemic encephalopathy.
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Terapia por Acupuntura , Córtex Cerebral/patologia , Homeostase , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/terapia , Receptores Opioides delta/metabolismo , Animais , Animais Recém-Nascidos , Feminino , Glucose/deficiência , Oxigênio , Potássio/metabolismo , Ratos Sprague-DawleyRESUMO
Previous studies have demonstrated that acupuncture is beneficial to patients with Crohn's disease (CD), but the mechanism underlying its therapeutic effects remains unclear. To identify the mechanism by which acupuncture treats CD, the balance between Th17 and Treg cells was assessed in CD patients. In this study, Ninety-two CD patients were randomly and equally assigned to a treatment group that were treated with herb-partitioned moxibustion and acupuncture or a control group with wheat bran-partitioned moxibustion and superficial acupuncture. The effect of these treatments on Th17 and Treg cells and their related molecular markers in the intestinal mucosa were detected before (week 0) and after (week 12) treatment. The results suggested that the ratio of Th17 and Treg cells was significantly decreased after treatment and that the levels of IL-17 and RORγt in the intestinal mucosa were obviously reduced, while the expression of FOXP3 was increased after treatment in both groups. In the treatment group, the expression of these molecules was more markedly regulated than the control group. In conclusion, moxibustion and acupuncture have been shown to regulate the ratio of Th17 and Treg cells in the intestinal mucosa of CD patients and restore the balance between these immune cell subsets.
RESUMO
Mast cells are found abundant at sites of acupoints. Nerve cells share perivascular localization with mast cells. Acupuncture (mechanical stimuli) can activate mast cells to release adenosine triphosphate (ATP) which can activate nerve cells and modulates pain-processing pathways in response to acupuncture. In this paper, a mathematical model was constructed for describing intracellular Ca(2+) signal and ATP release in a coupled mast cell and nerve cell system induced by mechanical stimuli. The results showed mechanical stimuli lead to a intracellular Ca(2+) rise in the mast cell and ATP release, ATP diffuses in the extracellular space (ECS) and activates the nearby nerve cells, then induces electrical current in the nerve cell which spreads in the neural network. This study may facilitate our understanding of the mechanotransduction process induced by acupuncture and provide a methodology for quantitatively analyzing acupuncture treatment.