RESUMEN
Background and aim: We have previously reported that histamine H1 receptor antagonists facilitate electroacupuncture (EA) analgesia in experimental animals. In this pilot study, we sought to determine whether the histamine H1 receptor antagonist dexchlorpheniramine (DCPA) facilitates EA analgesia in healthy human subjects. Experimental procedure: Forty healthy subjects aged 20-30 years were randomly allocated to 1 of 4 groups: (1) sham EA at acupoints Zusanli (ST36) and Yanglingquan (GB34) (sham EA; n = 10); (2) EA at ST36 and GB34 (n = 10); (3) EA at ST36 and GB34 plus low-dose DCPA (2 mg, n = 10); (4) EA at ST36 and GB34 plus high-dose DCPA (4 mg, n = 10). Before and after acupuncture treatment, pain thresholds were determined by transcutaneous electrical stimuli on the glabrous skin of the left upper arm. Results: After the acupuncture session, subjects in the EA plus high-dose DCPA group had a significantly higher pain threshold elevation compared with the other 3 study groups. The change from baseline in pain threshold in the EA plus high-dose DCPA group was significantly greater than the change in pain threshold with EA only, indicating that DCPA 4 mg facilitated EA analgesia. Conclusion: The results suggest that combining H1 receptor antagonist treatment with EA appears to relieve pain to a greater extent compared with EA alone. This study is registered with ClinicalTrials.gov (https://clinicaltrials.gov/), number NCT03805035 (https://clinicaltrials.gov/ct2/show/NCT03805035).
RESUMEN
Background: Acupuncture or electroacupuncture (EA) appears to be a potential treatment in acute clinical traumatic brain injury (TBI); however, it remains uncertain whether acupuncture affects post-TBI histone deacetylase (HDAC) expression or impacts other biochemical/neurobiological events. Materials and methods: We used behavioral testing, Western blot, and immunohistochemistry analysis to evaluate the cellular and molecular effects of EA at LI4 and LI11 in both weight drop-impact acceleration (WD)- and controlled cortical impact (CCI)-induced TBI models. Results: Both WD- and CCI-induced TBI caused behavioral dysfunction, increased cortical levels of HDAC1 and HDAC3 isoforms, activated microglia and astrocytes, and decreased cortical levels of BDNF as well as its downstream mediators phosphorylated-Akt and phosphorylated-GSK-3ß. Application of EA reversed motor, sensorimotor, and learning/memory deficits. EA also restored overexpression of HDAC1 and HDAC3, and recovered downregulation of BDNF-associated signaling in the cortex of TBI mice. Conclusion: The results strongly suggest that acupuncture has multiple benefits against TBI-associated adverse behavioral and biochemical effects and that the underlying mechanisms are likely mediated by targeting HDAC overexpression and aberrant BDNF-associated Akt/GSK-3 signaling.
RESUMEN
BACKGROUND: No reports exist as to neuroprotective effects associated with topical activation of transient receptor potential melastatin 8 (TRPM8), a noted cold receptor. In the present study, we identified whether activating peripheral TRPM8 can be an adjuvant therapy for ischemic stroke. METHODS: Menthol, an agonist of TRPM8, was applied orally or topically to all paws or back of the mouse after middle cerebral artery occlusion (MCAO). We used Trpm8 gene knockout (Trpm8-/-) mice or TRPM8 antagonist and lidocaine to validate the roles of TRPM8 and peripheral nerve conduction in menthol against ischemic stroke. RESULTS: Application of menthol 16% to paw derma attenuated infarct volumes and ameliorated sensorimotor deficits in stroke mice induced by MCAO. The benefits of topically applied menthol were associated with reductions in oxidative stress, neuroinflammation and infiltration of monocytes and macrophages in ischemic brains. Antagonizing TRPM8 or Trpm8 knockout dulls the neuroprotective effects of topically application of menthol against MCAO. Immunohistochemistry analyses revealed significantly higher TRPM8 expression in skin tissue samples obtained from the paws compared with skin from the backs, which was reflected by significantly smaller infarct lesion volumes and better sensorimotor function in mice treated with menthol on the paws compared with the back. Blocking conduction of peripheral nerve in the four paws reversed the neuroprotective effects of topical menthol administrated to paws. On the other hand, oral menthol dosing did not assist with recovery from MCAO in our study. CONCLUSION: Our results suggested that activation of peripheral TRPM8 expressed in the derma tissue of limbs with sufficient concentration of menthol is beneficial to stroke recovery. Topical application of menthol on hands and feet could be a novel and simple-to-use therapeutic strategy for stroke patients.
Asunto(s)
Accidente Cerebrovascular Isquémico , Mentol , Fármacos Neuroprotectores , Canales Catiónicos TRPM , Animales , Infarto/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Mentol/farmacología , Mentol/uso terapéutico , Ratones , Canales Catiónicos TRPM/genéticaRESUMEN
The meridian and collateral theory in traditional Chinese medicine (TCM) provides practitioners with essential guidance about the complex network of meridians and collateral systems, as well as informing discussions on physiopathology, diagnoses, and treatments. Various translations have enabled nonnative Chinese to understand the intricacy of the meridian pathways. However, original meanings are easily lost in the text transcription and translation, leading to misinterpretation and confusion in the learning process. We set out to (a) review the standard glossary that describes the meridian pathways; (b) review English translations of the bladder meridian pathway in selected sources; and (c) propose more accurate English translations of both. Our proposed texts offer preliminary guidance on the standardization of the terminology describing the meridian pathways and remind us of the importance of being as precise as possible when translating TCM literature, so that the work retains its original meaning.
Asunto(s)
Meridianos , Pueblo Asiatico , Humanos , Medicina Tradicional ChinaRESUMEN
Systemic growth differentiation factor 11 (GDF11) treatment improves the vasculature in the hippocampus and cortex in mice in recent studies. However, systemic application of recombinant GDF11 (rGDF11) cannot cross the brain blood barrier (BBB). Thus, large doses and long-term administration are required, while systemically applied high-dose rGDF11 is associated with deleterious effects, such as severe cachexia. This study tested whether in situ low dosage rGDF11 (1 µg/kg) protects the brain against ischemic stroke and it investigated the underlying mechanisms. Fibrin glue mixed with rGDF11 was applied to the surgical cortex for the slow release of rGDF11 in mice after permanent middle cerebral artery occlusion (MCAO). In situ rGDF11 improved cerebral infarction and sensorimotor function by upregulating Smad2/3 and downregulating FOXO3 expression. In situ rGDF11 was associated with reductions in protein and lipid oxidation, Wnt5a, iNOS and COX2 expression, at 24 h after injury. In situ rGDF11 protected hippocampal neurons and subventricular neural progenitor cells against MCAO injury, and increased newborn neurogenesis in the peri-infarct cortex. Systematic profiling and qPCR analysis revealed that Pax5, Sox3, Th, and Cdk5rap2, genes associated with neurogenesis, were increased by in situ rGDF11 treatment. In addition, greater numbers of newborn neurons in the peri-infarct cortex were observed with in situ rGDF11 than with systemic application. Our evidence indicates that in situ rGDF11 effectively decreases the extent of damage after ischemic stroke via antioxidative, anti-inflammatory and proneurogenic activities. We suggest that in situ slow-release rGDF11 with fibrin glue is a potential therapeutic approach against ischemic stroke.
Asunto(s)
Antiinflamatorios/administración & dosificación , Antioxidantes/administración & dosificación , Encéfalo/efectos de los fármacos , Factores de Diferenciación de Crecimiento/administración & dosificación , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Administración Tópica , Animales , Antiinflamatorios/química , Antioxidantes/química , Conducta Animal/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/fisiopatología , Preparaciones de Acción Retardada , Modelos Animales de Enfermedad , Composición de Medicamentos , Regulación de la Expresión Génica , Factores de Diferenciación de Crecimiento/química , Fuerza de la Mano , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Infarto de la Arteria Cerebral Media/fisiopatología , Mediadores de Inflamación/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/patología , Accidente Cerebrovascular Isquémico/fisiopatología , Ratones Endogámicos C57BL , Actividad Motora/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Proteínas Recombinantes/farmacología , Vía de Señalización WntRESUMEN
Osteoblasts and osteoclasts are major cellular components in the bone microenvironment and they play a key role in the bone turnover cycle. Many risk factors interfere with this cycle and contribute to bone-wasting diseases that progressively destroy bone and markedly reduce quality of life. Melatonin (N-acetyl-5-methoxy-tryptamine) has demonstrated intriguing therapeutic potential in the bone microenvironment, with reported effects that include the regulation of bone metabolism, acceleration of osteoblastogenesis, inhibition of osteoclastogenesis and the induction of apoptosis in mature osteoclasts, as well as the suppression of osteolytic bone metastasis. This review aims to shed light on molecular and clinical evidence that points to possibilities of melatonin for the treatment of both osteoporosis and osteolytic bone metastasis. It appears that the therapeutic qualities of melatonin supplementation may enable existing antiresorptive osteoporotic drugs to treat osteolytic metastasis.
Asunto(s)
Antioxidantes/farmacología , Neoplasias Óseas/prevención & control , Melatonina/farmacología , Osteoclastos/efectos de los fármacos , Osteogénesis , Osteoporosis/prevención & control , Animales , Neoplasias Óseas/secundario , Humanos , Osteoclastos/citología , Osteoporosis/patologíaRESUMEN
Acupuncture has been used for treating drug addiction since the 1970s, but little is known about the mechanisms by which acupuncture affects drug cue-induced relapse. The transcription factor delta-FosB (ΔFosB) plays a critical role in behavior and pathology after chronic use of cocaine. ΔFosB regulates glutamate receptor signaling and dendritic spine morphology in animal models. This experimental study compared the effects of electroacupuncture (EA) at acupoints LI4 and LI11 with those of another potentially beneficial intervention, gabapentin (GBP), alone or in combination, on reinstatement of cocaine-induced conditioned place preference (CPP) and levels of ΔFosB and glutamate receptor subunit 2 (GluR2) expression in the nucleus accumbens (NAc). EA at LI4 and LI11 significantly prevented cue-induced cocaine CPP reinstatement, whereas needle insertion without electrical stimulation at these acupoints had no such effect. EA also significantly attenuated cocaine-induced increases in ΔFosB and GluR2 expression in the NAc. Unexpectedly, these effects were reversed when GBP was combined with EA. Treatment with EA at LI4 and LI11 prevented cocaine-induced increases in dendritic spine density in the NAc core and shell. Our results suggest that EA at LI4 and LI11 may prevent cocaine relapse by modulating ΔFosB and GluR2 expression, as well as dendritic spine density.
Asunto(s)
Trastornos Relacionados con Cocaína/genética , Electroacupuntura , Proteínas Proto-Oncogénicas c-fos/genética , Receptores AMPA/genética , Animales , Trastornos Relacionados con Cocaína/terapia , Expresión Génica , Masculino , Ratones Endogámicos ICR , Regulación hacia ArribaRESUMEN
Background: Chemotherapy is suspected to be a risk factor for stroke in patients with cancer, athough the results from large-scale studies are controversial. Few strategies are available for reducing the stroke-related risks. Methods: We analyzed stroke incidence rates in Taiwan's Longitudinal Health Insurance database 2000 (LHID2000) for patients aged ≥20 years with newly-diagnosed cancer between Jan 1, 2000 and Dec 31, 2006, who did or did not receive chemotherapy. Moreover, we compared stroke incidence rates among chemotherapy users who did or did not use traditional Chinese medicine. All study participants were followed-up for 5 years or until they had a stroke. Results: In adjusted Kaplan-Meier analysis, the incidence of stroke was higher within the first year of cancer diagnosis among chemotherapy recipients compared with those who did not receive chemotherapy (31.1 vs. 9.75; adjusted subdistribution hazard ratio [sHR] 2.21; 95% confidence interval [CI], 1.52-3.20; p < 0.001). This between-group difference persisted at 4 years of follow-up (13.6 vs. 5.42; adjusted sHR 1.94; 95% CI, 1.53-2.46; p < 0.001). Similarly, the 5-year incidence rate of stroke was significantly lower among chemotherapy recipients using TCM vs. non-TCM users (0.19 vs. 0.46; adjusted sHR 0.45; 95% CI, 0.26-0.79; p < 0.001), as was the mortality rate (adjusted sHR 0.55; 95% CI, 0.44-0.68; p < 0.001). Conclusion: These Taiwanese data suggest that chemotherapy is a risk factor for stroke and that the use of TCM can significantly mitigate this risk. TCM also appears to reduce the mortality risk associated with chemotherapy.
RESUMEN
The CCN family of matricellular proteins (CYR61/CCN1, CTGF/CCN2, NOV/CCN3 and WISP1-2-3/CCN4-5-6) are essential players in the key pathophysiological processes of angiogenesis, wound healing and inflammation. These proteins are well recognized for their important roles in many cellular processes, including cell proliferation, adhesion, migration and differentiation, as well as the regulation of extracellular matrix differentiation. Substantial evidence implicates four of the proteins (CCN1, CCN2, CCN3 and CCN4) in the inflammatory pathologies of rheumatoid arthritis (RA) and osteoarthritis (OA). A smaller evidence base supports the involvement of CCN5 and CCN6 in the development of these diseases. This review focuses on evidence providing insights into the involvement of the CCN family in RA and OA, as well as the potential of the CCN proteins as therapeutic targets in these diseases.
Asunto(s)
Artritis Reumatoide/fisiopatología , Proteínas CCN de Señalización Intercelular/metabolismo , Osteoartritis/fisiopatología , Animales , Artritis Reumatoide/metabolismo , Humanos , Osteoartritis/metabolismoRESUMEN
With almost no community-transmitted cases and without any complete lockdown throughout 2020, Taiwan is one of very few countries worldwide that has recorded minimal impact from the COVID-19 pandemic attack. This is despite being only 130 km from China and having frequent business communications with that country, where COVID-19 first emerged. At the end of December 2020, Taiwan had recorded just 873 cases and 7 deaths, in a country of around 24 million people. How to determine the effectiveness of public health policies is an important issue that must be resolved, especially in those countries that have experienced few cases of community-transmitted COVID-19. Our analysis of epidemiological data in Taiwan relating to influenza-like illness (ILI), enterovirus and diarrhoea from the past 3 years reveals dramatic reductions in the incidence of ILI and enterovirus in 2020, compared with 2018 and 2019. These reductions occurred within 2 weeks of the government issuing public health policies for COVID-19 and indicate that such policies can effectively reduce infectious diseases overall. In contrast, no such reduction in ILI activity was observed in 2020 after the first COVID-19 case was reported in the USA. We suggest that infectious diseases data can be used to inform effective public health policies needed to break the transmission chain of COVID-19 and that ongoing monitoring of infectious diseases data can provide confidence about nationwide health.
Asunto(s)
COVID-19 , Control de Enfermedades Transmisibles , Pandemias/prevención & control , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/transmisión , Humanos , SARS-CoV-2 , Taiwán/epidemiologíaRESUMEN
Rheumatoid arthritis (RA) is an inflammatory joint disorder characterized by synovial proliferation and inflammation, with eventual joint destruction if inadequately treated. Modern therapies approved for RA target the proinflammatory cytokines or Janus kinases that mediate the initiation and progression of the disease. However, these agents fail to benefit all patients with RA, and many lose therapeutic responsiveness over time. More effective or adjuvant treatments are needed. Melatonin has shown beneficial activity in several animal models and clinical trials of inflammatory autoimmune diseases, but the role of melatonin is controversial in RA. Some research suggests that melatonin enhances proinflammatory activities and thus promotes disease activity in RA, while other work has documented substantial anti-inflammatory and immunoregulatory properties of melatonin in preclinical models of arthritis. In addition, disturbance of the circadian rhythm is associated with RA development and melatonin has been found to affect clock gene expression in joints of RA. This review summarizes current understanding about the immunopathogenic characteristics of melatonin in RA disease. Comprehensive consideration is required by clinical rheumatologists to balance the contradictory effects.
Asunto(s)
Artritis Reumatoide/metabolismo , Susceptibilidad a Enfermedades , Melatonina/metabolismo , Animales , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/etiología , Artritis Reumatoide/patología , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/metabolismo , Enfermedades Autoinmunes/patología , Relojes Circadianos , Ritmo Circadiano , Citocinas/metabolismo , Manejo de la Enfermedad , Humanos , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismoRESUMEN
The extensive involvement of the endocannabinoid system (ECS) in vital physiological and cognitive processes of the human body has inspired many investigations into the role of the ECS and drugs, and therapies that target this system and its receptors. Activation of cannabinoid receptors 1 and 2 (CB1 and CB2) by cannabinoid treatments, including synthetic cannabinoids, alleviates behavioral responses to inflammatory and neuropathic pain. An increasing body of scientific evidence details how electroacupuncture (EA) treatments achieve effective analgesia and reduce inflammation by modulating cannabinoid signaling, without the adverse effects resulting from synthetic cannabinoid administration. CB1 receptors in the ventrolateral area of the periaqueductal gray are critically important for the mechanisms of the EA antinociceptive effect, while peripheral CB2 receptors are related to the anti-inflammatory effects of EA. This review explores the evidence detailing the endocannabinoid mechanisms involved in EA antinociception.
RESUMEN
Pain is a major primary health care problem. Emerging studies show that inhibition of spinal microglial activation reduces pain. However, the precise mechanisms by which microglial activation contributes to nociceptive synaptic transmission remain unclear. In this study, we measured spontaneous synaptic activity of miniature excitatory postsynaptic currents (mEPSCs) in rat spinal cord superficial dorsal horn (SDH, laminae I and II) neurons. Lipopolysaccharide (LPS) and adenosine triphosphate (ATP) increased the frequency, but not amplitude, of mEPSCs in SDH neurons. Microglial inhibitors minocycline and paeonol, as well as an astrocyte inhibitor, a P2Y1 receptor (P2Y1R) antagonist, and a metabotropic glutamate receptor 5 (mGluR5) antagonist, all prevented LPS-induced enhancement of mEPSC frequency. In mouse behavioral testing, minocycline and paeonol effectively reduced acetic acid-induced writhing and LPS-induced hyperalgesia. These results indicate that LPS-activated microglia release ATP, which stimulates astrocyte P2Y1Rs to release glutamate, triggering presynaptic mGluR5 receptors and increasing presynaptic glutamate release, leading to an increase in mEPSC frequency and enhancement of nociceptive transmission in SDH neurons. We propose that these effects can serve as a new electrophysiological model for evaluating pain. Moreover, we predict that pharmacologic agents capable of inhibiting the LPS-induced enhancement of mEPSC frequency in SDH neurons will have analgesic effects.
Asunto(s)
Potenciales Postsinápticos Excitadores/efectos de los fármacos , Hiperalgesia , Lipopolisacáridos/toxicidad , Modelos Neurológicos , Dolor , Células del Asta Posterior/metabolismo , Adenosina Trifosfato/farmacología , Animales , Hiperalgesia/inducido químicamente , Hiperalgesia/metabolismo , Hiperalgesia/patología , Hiperalgesia/fisiopatología , Masculino , Ratones , Dolor/inducido químicamente , Dolor/metabolismo , Dolor/patología , Dolor/fisiopatología , Células del Asta Posterior/patología , Ratas , Ratas Sprague-DawleyRESUMEN
Introduction: Human chondrosarcomas (CS; a malignant cartilage-forming bone tumor) respond poorly to chemotherapy and radiation treatment, resulting in high morbidity and mortality rates. Expanded treatment options are urgently needed. Areas covered: This article updates our 2014 review, in which we evaluated the CS treatments available at that time and potential treatment options under investigation. Since then, advances in research findings, particularly from Chinese herbal medicines, may be bringing us closer to more effective therapies for CS. In particular, promising findings have been reported from research targeting platelet-derived growth factor receptor. Expert opinion: Few treatment options exist for CS; chemotherapy is not even an option for unresectable disease, in which 5-year survival rates are just 2%. New information about the multitude of genes and signaling pathways that encourage CS growth, invasion and metastasis are clarifying how certain signaling pathways and plant-derived active compounds, especially molecularly-targeted therapies that inhibit the PDGF receptor, interfering with these biological processes. This review summarizes discoveries from the last 5 years and discusses how these findings are fueling ongoing work into effectively dealing with the disease process and improving the treatment of CS.
Asunto(s)
Neoplasias Óseas/terapia , Condrosarcoma/terapia , Terapia Molecular Dirigida , Animales , Neoplasias Óseas/patología , Condrosarcoma/patología , Humanos , Invasividad Neoplásica , Metástasis de la Neoplasia , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Transducción de Señal , Tasa de SupervivenciaRESUMEN
Neuropsychiatric disorders, including depression, anxiety, schizophrenia, and Alzheimer's disease (AD), are diseases that are directly or indirectly associated with cerebral dysfunction and contribute significantly to disability in adult populations worldwide. Important limitations surround the currently available pharmacologic agents for neuropsychiatric disorders and, moreover, many patients fail to respond to these therapies. Acupuncture might be a complementary therapy for neuropsychiatry disorders. In this review, we investigate the current evidence for the treatment efficacy of acupuncture in depression, anxiety, schizophrenia, and AD. Secondly, we review recent advances in understanding of the dysregulated glutamate system underlying the pathophysiology of these disorders. Finally, we discuss the ways in which acupuncture treatment can potentially modulate glutamate receptors and excitatory amino acid transporters. We conclude that the treatment effects of acupuncture may be underpinned by its intervention in the dysregulated glutamate system. Further preclinical and clinical studies are needed to clarify the possible mechanisms of acupuncture in these neuropsychiatric disorders and to establish protocols for treatment guidelines.
RESUMEN
Angiogenesis, the growth of new blood vessels, is essential in the pathogenesis of joint inflammatory disorders such as rheumatoid arthritis (RA) and osteoarthritis (OA), facilitating the invasion of inflammatory cells and increase in local pain receptors that contribute to structural damage and pain. The angiogenic process is perpetuated by various mediators such as growth factors, primarily vascular endothelial growth factor (VEGF) and hypoxia-inducible factors (HIFs), as well as proinflammatory cytokines, various chemokines, matrix components, cell adhesion molecules, proteases, and others. Despite the development of potent, well-tolerated nonbiologic (conventional) and biologic disease-modifying agents that have greatly improved outcomes for patients with RA, many remain resistant to these therapies, are only partial responders, or cannot tolerate biologics. The only approved therapies for OA include symptom-modifying agents, such as analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), steroids, and hyaluronic acid. None of the available treatments slow the disease progression, restore the original structure or enable a return to function of the damaged joint. Moreover, a number of safety concerns surround current therapies for RA and OA. New treatments are needed that not only target inflamed joints and control articular inflammation in RA and OA, but also selectively inhibit synovial angiogenesis, while preventing healthy tissue damage. This narrative review of the literature in PubMed focuses on the evidence illustrating the therapeutic benefits of modulating angiogenic activity in experimental RA and OA. This evidence points to new treatment targets in these diseases.
Asunto(s)
Artritis Reumatoide/metabolismo , Neovascularización Patológica/metabolismo , Osteoartritis/metabolismo , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Citocinas/genética , Citocinas/metabolismo , Regulación de la Expresión Génica , Humanos , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/genética , Osteoartritis/tratamiento farmacológico , Osteoartritis/genética , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Pruritus, or itch, is a frequent complaint amongst patients with cholestatic hepatobiliary disease and is difficult to manage, with many patients refractory to currently available antipruritic treatments. In this study, we examined whether manual acupuncture (MA) at particular acupoints represses deoxycholic acid (DCA)-induced scratching behavior and microglial activation and compared these effects with those induced by another pruritogen, 5'-guanidinonaltrindole (GNTI, a kappa opioid receptor antagonist). MA at Hegu (LI4) and Quchi (LI11) acupoints significantly attenuated DCA- and GNTI-induced scratching, whereas no such effects were observed at the bilateral Zusanli acupoints (ST36). Interestingly, GNTI-induced scratching was reduced similarly by both MA and electroacupuncture (EA) at the LI4 and LI11 acupoints. MA at non-acupoints did not affect scratching behavior. Intraperitoneal injection of minocycline (a microglial inhibitor) reduced GNTI- and DCA-induced scratching behavior. In Western blot analysis, subcutaneous DCA injection to the back of the neck increased spinal cord expression of ionized calcium-binding adapter molecule 1 (Iba1) and tumor necrosis factor-alpha (TNF-α) as compared with saline injection, while MA at LI4 and LI11 reduced these DCA-induced changes. Immunofluorescence confocal microcopy revealed that DCA-induced Iba1-positive cells with thicker processes emanated from the enlarged cell bodies, while this effect was attenuated by pretreatment with MA. It is concluded that microglia and TNF-α play important roles in the itching sensation and MA reduces DCA-induced scratching behavior by alleviating spinal microglial activation. MA may be an effective treatment for cholestatic pruritus.
Asunto(s)
Terapia por Acupuntura , Ácidos y Sales Biliares/efectos adversos , Microglía/metabolismo , Prurito/terapia , Factor de Necrosis Tumoral alfa/fisiología , Animales , Humanos , Masculino , Ratones , Ratones Endogámicos ICR , Prurito/etiologíaRESUMEN
Paeonol is a major constituent of the Chinese herb Moutan cortex radices. Recent studies report that paeonol has neuroprotective effects and improves impaired learning and memory. However, its underlying mechanisms by which paeonol contributes to synaptic transmission remain unclear. In this study, we found that paeonol increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) and spontaneous excitatory postsynaptic currents (sEPSCs), but had no effect on the amplitude in rat hippocampal CA1 neurons. Similarly, the acetylcholinesterase (AChE) inhibitor rivastigmine increased the frequency of mEPSCs, but had no effect upon amplitude in rat hippocampal neurons. Rivastigmine also inhibited the delayed outward K+ currents in rat hippocampal CA1 neurons, but had no effect in nucleus ambiguus (NA) neurons. The Kv2 blocker guangxitoxin-1E increased the frequency of both mEPSCs and sEPSCs of rat hippocampal CA1 neurons, without affecting their amplitude. Our results suggest that paeonol and rivastigmine enhance spontaneous presynaptic transmitter release, which may be associated with the inhibition of the hippocampal Kv2 current and with therapeutic potential in neurotransmitter deficits found in Alzheimer's disease (AD). Moreover, our data also show that paeonol protects against Aß25-35-induced impairment of long-term potentiation (LTP) in mouse hippocampal neurons. However, guangxitoxin-1E failed to potentiate the evoked field excitatory postsynaptic potentials (fEPSPs), LTP and Aß25-35-induced impairment of LTP. These results indicate that paeonol may has the potential to improve learning and memory in AD. Interestingly, this effect is not involved in the inhibition of the hippocampal Kv2 current.
Asunto(s)
Acetofenonas/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/fisiología , Canales de Potasio Shab/metabolismo , Transmisión Sináptica/efectos de los fármacos , Animales , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Hipocampo/citología , Hipocampo/metabolismo , Potenciación a Largo Plazo/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
This study investigated the influence of the histamine H1 receptor antagonists, chlorpheniramine (CHL) and pyrilamine, on the analgesic effects of acupuncture in mice. Nociceptive response was evaluated by the acetic acid-induced abdominal writhe test. Electroacupuncture (EA) at bilateral ST36 reduced the manifestations of acetic acid-induced abdominal writhing, whereas needle insertion without electrostimulation had no such effect. Notably, EA treatment was not associated with any analgesic effects in mice pretreated with naloxone. Low doses of CHL (0.6[Formula: see text]mg/kg; p.o.) or pyrilamine (2.5[Formula: see text]mg/kg; i.p.) as monotherapy did not affect acetic acid-induced abdominal writhing. However, when each agent was combined with EA, acetic acid-induced abdominal writhing was reduced by a greater extent when compared with EA alone. Interestingly, the effects of CHL on acupuncture analgesia were not completely reversed by naloxone treatment. Acetic acid induced increases of phospho-p38 expression in spinal cord, as determined by immunofluorescence staining and Western blot analysis. These effects were attenuated by EA at ST36 and by low doses of histamine H1 receptor antagonists, alone or in combination. Our findings show that relatively low doses of histamine H1 receptor antagonists facilitate EA analgesia via non-opioid receptors. These results suggest a useful strategy for increasing the efficacy of EA analgesia in a clinical situation.
Asunto(s)
Dolor Abdominal/fisiopatología , Dolor Abdominal/terapia , Clorfeniramina/administración & dosificación , Clorfeniramina/farmacología , Electroacupuntura , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/farmacología , Nocicepción/efectos de los fármacos , Nocicepción/fisiología , Pirilamina/administración & dosificación , Pirilamina/farmacología , Estimulación Eléctrica Transcutánea del Nervio/métodos , Dolor Abdominal/inducido químicamente , Ácido Acético/efectos adversos , Animales , Combinación de Medicamentos , Masculino , Ratones Endogámicos ICR , Dimensión del DolorRESUMEN
Acupuncture is recommended by the World Health Organization (WHO) as an alternative and complementary strategy for stroke treatment and for improving stroke care. Clinical trial and meta-analysis findings have demonstrated the efficacy of acupuncture in improving balance function, reducing spasticity, and increasing muscle strength and general well-being post-stroke. The mechanisms underlying the beneficial effects of acupuncture in stroke rehabilitation remain unclear. The aim of this study was to conduct a literature review, summarize the current known mechanisms in ischemic stroke rehabilitation through acupuncture and electroacupuncture (EA) therapy, and to detail the frequently used acupoints implicated in these effects. The evidence in this review indicates that five major different mechanisms are involved in the beneficial effects of acupuncture/EA on ischemic stroke rehabilitation: (1) Promotion of neurogenesis and cell proliferation in the central nervous system (CNS); (2) Regulation of cerebral blood flow in the ischemic area; (3) Anti-apoptosis in the ischemic area; (4) Regulation of neurochemicals; and, (5) Improvement of impaired long-term potentiation (LTP) and memory after stroke. The most frequently used acupoints in basic studies include Baihui (GV20), Zusanli (ST36), Quchi (LI11), Shuigou (GV26), Dazhui (GV14), and Hegu (LI4). Our findings show that acupuncture exerts a beneficial effect on ischemic stroke through modulation of different mechanisms originating in the CNS.