Antihistamine promotes electroacupuncture analgesia in healthy human subjects: A pilot study.

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).

Electroacupuncture improves TBI dysfunction by targeting HDAC overexpression and BDNF-associated Akt/GSK-3ß signaling.

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.

A Review of the Traditional Chinese Medicine Glossary of Meridian Pathways and Its English Translations.

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.

Melatonin Inhibits Osteoclastogenesis and Osteolytic Bone Metastasis: Implications for Osteoporosis.

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.

Electroacupuncture prevents cocaine-induced conditioned place preference reinstatement and attenuates ΔFosB and GluR2 expression.

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.

Traditional Chinese Medicine Reduces the Incidence of Chemotherapy-Induced Stroke: A Five-Year Nationwide Population-Based Cohort Study From Taiwan.

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.

Reconsidering the Role of Melatonin in Rheumatoid Arthritis.

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.

The Endocannabinoid System Contributes to Electroacupuncture Analgesia.

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.

An update on current and future treatment options for chondrosarcoma.

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.

The Effects of Acupuncture on Glutamatergic Neurotransmission in Depression, Anxiety, Schizophrenia, and Alzheimer's Disease: A Review of the Literature.

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.

Manual acupuncture relieves bile acid-induced itch in mice: the role of microglia and TNF-α.

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.

Histamine H1 Receptor Antagonists Facilitate Electroacupuncture Analgesia.

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.

Mechanisms of Acupuncture Therapy in Ischemic Stroke Rehabilitation: A Literature Review of Basic Studies.

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.

Electroacupuncture inhibits pruritogen-induced spinal microglial activation in mice.

In this study, we examined whether electroacupuncture (EA) represses pruritogen-induced microglial activation. Immunohistochemical studies revealed that a subcutaneous (s.c.) injection of the pruritogen 5'-guanidinonaltrindole (GNTI; 0.3mg/kg) to the back of the neck in mice induced acute expression of the ionized calcium-binding adaptor molecule 1 (Iba1) in both gray and white matter of the spinal cord, with the highest expression in the dorsal horn area. EA application (2Hz) to LI4 and LI11 attenuated GNTI-induced scratching behavior and repressed GNTI-induced Iba1 expression and Iba1 (+) microglia in the dorsal horn. In contrast, EA at the ST36 acupoint had no such effects. Confocal image analysis revealed co-expression of phosphorylated p38 and Iba1 in microglia with EA at the ST36 acupoint, but not at the LI4 or LI11 acupoints. In Western blot analysis, s.c. injection of GNTI to the back of the neck increased Iba1 and phospho-p38 expression in the spinal cord as compared with injection of saline, while EA at LI4 and LI11 reduced GNTI-induced expression of Iba1 and phospho-p38. These findings indicate that EA at LI4 and LI11, but not at ST36, reduces GNTI-induced microglial activation in the mouse spinal cord.

The possible role of stem cells in acupuncture treatment for neurodegenerative diseases: a literature review of basic studies.

This review reports on recent findings concerning the effects of acupuncture and electroacupuncture (EA) on stem cell mobilization and differentiation, in particular with regard to neurogenesis. Traditional Chinese acupuncture has a history of over 2,500 years and is becoming more popular worldwide. Evidence has demonstrated that acupuncture may be of benefit in stroke rehabilitation, parkinsonism, dementia, and depression. This article reviews recent studies concerning the effects of acupuncture/EA on stem cell mobilization and on progenitor cell proliferation in the CNS. The reviewed evidence indicates that acupuncture/EA has beneficial effects in several neurodegenerative diseases, and it may prove to be a nondrug method for mobilizing stem cells in the CNS.