NTPDase1-ATP-P2Y2Rs axis in the sciatic nerve contributes to acupuncture at "Zusanli" (ST36)-induced analgesia in ankle arthritis rats.

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.

Effect of 10.6-µm CO2 laser moxibustion on the fastest 15-m walking time in patients with knee osteoarthritis: a double-blind, sham-controlled, multi-site randomized trial.

BACKGROUND: In this study, we investigated the impact of 10.6-µm CO2 laser moxibustion (LM) on the fastest 15-m walking time in individuals suffering from knee osteoarthritis (KOA). METHODS: A total of 392 individuals diagnosed with KOA and meeting the specified eligibility criteria were assigned randomly into two groups: the LM treatment group and the sham LM control group (ratio 1:1). Both groups received either LM therapy or simulated LM therapy to address the affected area of the knee joint. This treatment was administered three times a week for a duration of 4 weeks. RESULTS: In the LM group, the fastest 15-m walking times at both Week 4 and Week 12 were significantly reduced compared to the times before treatment (all P < 0.05). However, in the sham LM group, there were no notable differences in the fastest 15-m walking times after treatment (all P > 0.05). Moreover, the LM group exhibited shorter 15-m walking times than the sham LM group at both Week 4 and Week 12 (all P < 0.05). CONCLUSION: The use of CO2 LM can lead to a substantial enhancement in the fastest 15-m walking time of individuals suffering from KOA, and its therapeutic impact can last for a minimum of 8 weeks post-treatment. The fastest 15-m walking time serves as an indicator of alterations in the walking capacity of patients with KOA.

Effect of 10.6 µm laser moxibustion on inflammation in diabetic peripheral neuropathy rats.

Diabetic peripheral neuropathy (DPN) is the main cause of disability in diabetes patients but the efficacy of available drugs is poor. Moxibustion is an adjunctive treatment for DPN that can reduce symptoms. The peak value of the far infrared wavelength of 10.6 µm laser moxibustion is close to the infrared radiation spectrum of traditional moxibustion. Its effect is similar to that of moxibustion and does not cause pain, infection or produce irritating smoke. Twenty-four male SD rats were divided into control (Con), DPN, laser moxibustion (LM), and pyrrolidine dithiocarbamate (PDTC) groups (n=6/group). The DPN, LM and PDTC group rats were intraperitoneally injected with 1% streptozotocin (STZ) to induce a model of DPN. LM group rats were irradiated with a laser at bilateral ST36 acupoints for 15 min, once every other day, for 14 days. PDTC group rats were intraperitoneally injected with PDTC once a day. Body weight, blood glucose, and paw withdrawal mechanical threshold (PWMT) were measured and laser speckle imaging (LSI) performed before and after modeling and at 1 and 2 weeks after intervention. Two weeks after intervention, changes in serum interleukin 1ß (IL1ß), interleukin 6 (IL6), tumor necrosis factor α (TNFα) and nerve growth factor (NGF) were analyzed, and the abundance of NF-κB and IκB-α proteins and levels of NF-κB and IκB-α mRNAs in the sciatic nerve were observed. The results showed that 10.6 µm laser moxibustion can relieve pain, improve microcirculation, and alleviate inflammation in DPN rats, possibly via the NF-κB inflammatory pathway.

A comparison of jade moxibustion and traditional moxibustion in the treatment of knee osteoarthritis: A randomized clinical trial.

BACKGROUND: This study was developed to compare the relative clinical efficacy of traditional moxibustion and Jade moxibustion in an effort to define the most effective approaches to treating knee osteoarthritis. METHODS: In total, 94 patients were randomly assigned at a 1:1 ratio to the traditional moxibustion (TM) and Jade moxibustion (JM) groups. For JM, a jade kneepad was preheated for 3 minutes via electrification, with the jade in the kneepad being pressed onto acupoints when reaching an initial temperature of 46°C. For patients in the TM group, moxa cones were applied to acupoints for treatment. In total, 12 treatments were performed for patients in each group, with treatment being conducted 3 times per week. Study outcomes included 36-item short-form health survey and Western Ontario and McMaster Universities Osteoarthritis Index knee stiffness scores. In addition, serum levels of osteoarthritis-related cytokines were measured. RESULTS: Overall, 89/94 patients completed this study, including 44 and 45 in the TM and JM groups, respectively. The 36-item short-form health survey physical functioning at weeks 12 and 24 (P = .033, 0.001), role-physical at weeks 4 and 24 (P = .030, 0.014), and role-emotional at week 4 (P = .045) were the only scores to differ significantly between the TM and JM groups. Western Ontario and McMaster Universities Osteoarthritis Index stiffness scores in the JM groups improved significantly relative to baseline at weeks 4, 8, 12, and 24 (all P < .01). The scores in the TM group differed significantly at all time points relative to baseline (all P < .01), with no differences between groups (all P > .05). Serum Interleukin-2 levels were lower in both groups (all P < .01). Cartilage oligomeric matrix protein and monocyte chemotactic protein-1 only differed significantly for patients treated via JM (P < .05, P < .01), with the same also being true for Interleukin-1ß and Interleukin-8 in the TM group (all P < .01). No significant differences in other cytokines were observed, nor did they differ significantly between groups (all P > .05). CONCLUSION: These results suggest that JM treatment can improve knee osteoarthritis patient quality of life, alleviating joint stiffness and restoring joint function with a level of efficacy comparable to TM.

Lateral hypothalamic orexin neurons mediate electroacupuncture-induced anxiolytic effects in a rat model of post-traumatic stress disorder.

The lateral hypothalamus' orexinergic system has been associated with anxiety-related behaviors, and electroacupuncture (EA) modifies orexin neurons to control the anti-anxiety process. However, in a rat model of post-traumatic stress disorder (PTSD), the important role of LH orexin neurons (OXNs) in the anxiolytic effects induced by EA has not been explored. In this study, rats underwent modified single prolonged stress (MSPS) for seven days before developing EA. The rats were then subjected to elevated plus maze (EPM) and open field (OFT) tests, and western blot and c-Fos/orexin double labeling investigations were carried out to determine the functional activation of LH orexinergic neurons. Compared to MSPS model rats, it has been demonstrated that EA stimulation enhanced the amount of time spent in the central zone (TSCZ) in OFT and the amount of time spent in the open arm (TSOA) in EPM in MSPS model rats (P < 0.01). After behavioral testing, MSPS model rats had decreased activated c-Fos positive OXNs. Still, EA in SPS rats increased that number and elevated orexin type 1 receptors (OXR1) protein expression in the LH. Furthermore, after administering SB334867 (an OXR1 antagonist) to MSPS model rats, the effects of EA therapy on anxiety-like behaviors (ALBs) were significantly diminished. Additionally, when low-dose orexin-A (LORXA) was administered intracerebroventricularly together with EA stimulation in MSPS rats, the anxiolytic effects of the stimulation were substantially enhanced (P < 0.05). The results of this study reveal the mechanisms by which acupuncture may reduce PTSD and advance our understanding of the function of LH orexin signaling in EA's anxiolytic effects.

[Non-linear characteristic of acupoint resistance and its application].

Acupoint specificity is a key scientific issue in acupuncture and moxibustion. Acupoint electric resistance is a commonly-used biophysical index to study the functional specificity of acupoints. The non-linear characteristics of acupoint electric resistance have great impacts on the measured values, but it has been greatly ignored. By analyzing the non-linear characteristics of acupoint resistance and its application in the study of acupoint function specificity, a new idea of introducing chaos theory and technology into the study of acupoint function is proposed.

Mast Cell-Associated Serotonin in Acupoint Contributes to Acupuncture Analgesia in Arthritis Rats by Mediating ATP Release.

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.

The real-time detection of acupuncture-induced extracellular ATP mobilization in acupoints and exploration of its role in acupuncture analgesia.

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.

New smokeless moxibustion for knee osteoarthritis: A study protocol for a multicenter, single-blind, randomized controlled trial.

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.

Low level light therapy/photobiomodulation for diabetic peripheral neuropathy: protocol of a systematic review and meta-analysis.

INTRODUCTION: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes that strongly impact the patients' quality of life and working ability. Evidence indicated that low level light therapy (LLLT)/photobiomodulation might be effective for neuropathy. However, the effect of LLLT for DPN is not clear. The objective of this systematic review and meta-analysis is to determine the effects and safety of LLLT/photobiomodulation for DPN, in comparison with other methods such as sham light, no treatment, other active treatment and LLLT as an additional treatment compared with another treatment alone. METHODS AND ANALYSIS: We will search eight databases from their inception to the date before the review submission. Randomised controlled trials (RCTs) will be included. Two reviewers will independently extract data using a structured data extraction method and assess the risk of bias in the included studies. Data will be synthesised using standardised mean difference or risk ratio with 95% CIs for continuous and dichotomous data, respectively. The primary outcome will be change in pain and secondary outcomes will include global symptom improvement, functional impairment and disability, impairment of sensation, quality of life, nerve conduction, and adverse events. Sensitivity and subgroup analysis will be employed to explore the influence of possible clinical and methodological characteristics. Publication bias will be assessed using funnel plot. We will conduct meta-analysis with RevMan V.5.4 and evaluate quality of the evidence using GRADE approach. ETHICS AND DISSEMINATION: This study does not require ethics approval. Our findings will be disseminated in the peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42021276056.

Lateral Hypothalamic Orexin Neurons Mediate the Reward Effects of Pain Relief Induced by Electroacupuncture.

The reward of pain relief caused by acupuncture has been found to be clinically significant. However, the molecular mechanisms underlying acupuncture-induced reward of pain relief in chronic pain remain unclear and have not been analyzed in suitable preclinical models. Here, we investigated whether acupuncture could potentially induce the reward of pain relief and orexin neuronal signaling in the lateral hypothalamus (LH) and exhibit a possible role in electroacupuncture (EA)-induced reward in spared nerve injury (SNI) rats. Therefore, by using conditioned place preference (CPP) paradigm, we noticed that EA induced the preference for cues associated with EA-induced pain relief in the early, but not late, phase of chronic pain. These observations were different from the immediate antihyperalgesic effects of EA. c-Fos/orexin double labeling revealed that EA stimulation on 14 days but not on 28 days after SNI modeling activated greater numbers of c-Fos positive orexin neurons in the LH after the CPP test. Moreover, the administration of an orexin-A antagonist in the LH significantly blocked the reward effects of pain relief induced by EA. Furthermore, by using cholera toxin b subunit combined with c-Fos detection, we found that the orexin circuit from the LH to the nucleus accumbens (NAc) shell was significantly activated after EA induced CPP. Microinjection of the orexin antagonist into the NAc shell substantially attenuated the CPP induced by EA. Intravenous injection of low-dose orexin-A together with EA resulted in significantly greater antihyperalgesia effects and CPP scores. Together, these findings clearly demonstrated that LH orexin signaling could potentially play a critical role in the reward effects of pain relief induced by acupuncture. The observations of the present study extended our understanding of orexin signaling in the LH and its role in EA-induced reward, providing new insights into the mechanisms of acupuncture analgesia.

[Bone proportional measurement on the chest and abdomen among 101 young females].

OBJECTIVE: To examine the bone proportional measurement standard on the chest and abdomen of modern women. METHODS: The height, weight and distances of bone proportional measurement chest and abdomen of 101 young females were measured. The height was divided by 75 to calculate the data of bone proportional measurement, and compared with the national standard published in 2006 and the ancient literature of Miraculous Pivot: Gudu. RESULTS: The bone proportional distances between two nipples and two coracoid processes of women were 8 cun and 12 cun respectively, which were in line with the 2006 national standard. The bone proportional distance from navel to superior margin of pubic symphysis (Qugu) was 6.5 cun, which was consistent with the ancient literature of Miraculous Pivot: Gudu. The bone proportional distance from suprasternal fossa to the middle point of xiphisternal synchondrosis (Qigu) was less than 9 cun, while the bone proportional distance from Qigu to navel was more than 8 cun, resulting in the ratio less than 9︰8. The bone proportional distance from suprasternal fossa to the middle point of xiphoid process was 9 cun, corresponding to the ratio of 9︰8 when comparing with the measurement from the middle point of xiphoid process to navel. CONCLUSION: The bone proportional distance measurement between two nipples and two coracoid processes of women should follow the 2006 national standard, and the bone proportional distance measurement from navel to superior margin of pubic symphysis should follow the standard of Miraculous Pivot: Gudu. The middle point of xiphisternal synchondrosis should be replaced by the middle point of xiphoid process.

A randomized sham-controlled trial of manual acupuncture for infertile women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex polygenic disease and is one of the most common endocrinological and reproductive disorders. The purpose of this study was to evaluate the efficacy of acupuncture combined with herbal medicine among infertile females with polycystic ovary syndrome (PCOS). METHOD: A total of 86 women with PCOS, experiencing infertility, were recruited and randomly assigned to receive either manual acupuncture (MA) or sham acupuncture (SA) twice per week for three menstrual cycles. Both groups received herbal medication. The evaluations were conducted after three menstrual cycles and 24 weeks' follow-up. RESULTS: The trial was completed by 79 (91.86%) of the 86 randomly selected patients. During this study, the pregnancy rate in the MA group (46.34%) was significantly higher than the SA group (18.42%), with a P-value of 0.008. Moreover, the ovulation rate of the MA group (58.14%) was higher than that of the SA group (45.74%), with a P-value of 0.046. The improvement rate of PCOS score and testosterone level showed a statistical difference between the two groups (P-values were <0.05). There were no other differences between the two groups. Sex hormones level, including E2, T, P, LH, and LH/FSH were significantly lower after intervention in the MA group (P-values were <0.05) compared with baseline, while only the progesterone level was reduced in the SA group (P-value = 0.008). CONCLUSION: Manual acupuncture combined with herbal medicine may be clinically useful for infertile women with PCOS in improving pregnancy and ovulation rate. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800014997.

10.6-µm infrared laser as adjuvant therapy for diabetic peripheral neuropathy: study protocol for a double-blind, randomized controlled trial.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common chronic neurological complication. It is the main cause of disability in diabetes mellitus (DM) patients and seriously affects the quality of life of patients. Pharmacological treatments always associate with limited efficacy and adverse effects. Moxibustion has been recommended to treat DPN as an adjuvant therapy to conventional medical treatment to accelerate alleviation of the symptoms of DPN. 10.6-µm laser moxibustion (LM), whose wavelength is close to the peak of infrared radiation spectrum of the traditional moxibustion as well as human acupoints, produces the thermal effect similar with moxibustion but with no smoke or smell. The purpose of this sham controlled clinical trial is to determine the effect and safety of 10.6-µm LM as adjuvant therapy in patients with DPN. METHODS: This is a protocol for a randomized, double-blind, sham-controlled trial. One hundred fourteen patients meeting the inclusion and exclusion criteria will be recruited and randomly assigned to the LM group or the sham LM group with a 1:1 allocation ratio. Patients in both groups will receive a basic integrated treatment of Chinese and Western medicine and a total of 12 sessions of true or sham LM treatments over 4 weeks with 3 sessions a week. The primary outcome is nerve conduction velocity (NCV), and the secondary outcomes include Michigan Neuropathy Screening Instrument (MNSI) scores, Diabetes-Specific Quality of Life (DSQL) scores, blood rheology parameters, and assessments of safety and blinding. Outcome measures will be collected at baseline, 2 weeks after treatment, the end of LM treatments (4 weeks), and 4, 8 weeks after the end of LM treatment (8, 12weeks). DISCUSSION: This study will be conducted to compare the efficacy of LM versus sham LM combined with medical treatment. 10.6-µm LM may alleviate symptoms, improve quality of life, and reduce the dosage of drugs as well as avoid causing serious side effects. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000029329 . Registered on 25 January 2020.

Frequency-Specific Blood Oxygen Level Dependent Oscillations Associated With Pain Relief From Ankle Acupuncture in Patients With Chronic Low Back Pain.

Objective: Recent advances in brain imaging have deepened our knowledge of the neural activity in distinct brain areas associated with acupuncture analgesia. However, there has not been conclusive research into the frequency-specific resting-state functional changes associated with acupuncture analgesia in patients with chronic pain. Here, we aimed to characterize changes across multiple frequencies of resting-state cortical activity associated with ankle acupuncture stimulation (AAS) in patients with chronic low back pain (CLBP) and healthy controls. Methods: Twenty seven patients with CLBP and Twenty five age- and gender-matched healthy volunteers were enrolled in the study. Participants received tactile sham acupuncture (TSA) and AAS, respectively. The whole-brain amplitude of low-frequency fluctuation (ALFF) in the range 0.01-0.25 Hz was assessed for changes associated with each intervention. Further, a visual analog scale (VAS) was used to collect subjective measures of pain intensity in patients. Linear mixed-effect modeling (LME) was used to examine the mean ALFF values of AAS and TSA between patients and healthy controls. Results: The ALFF was modulated in the default mode network (an increase in the medial prefrontal cortex, and a decrease in the cerebellum/posterior ingulate/parahippocampus, P < 0.01, corrected) in both patients and controls. Decreased ALFF in the bilateral insular was frequency-dependent. Modulations in the cerebellum and right insular were significantly correlated with VAS pain score after AAS (P < 0.01). Conclusion: Hence, frequency-specific resting-state activity in the cerebellum and insular was correlated to AAS analgesia. Our frequency-specific analysis of ALFF may provide novel insights related to pain relief from acupuncture.

Comparison of 10.6 µm Laser Moxibustion with Traditional Moxibustion in Knee Osteoarthritic Therapy: A Randomized Noninferiority Clinical Trial.

Objective: To investigate the noninferiority of 10.6 µm laser moxibustion (LM) to traditional moxibustion (TM) in knee osteoarthritis (KOA). Methods: Ninety-two patients were recruited and randomly placed into one of two groups: 10.6 µm LM or TM in a 1:1 ratio. Each patient received 12 sessions of LM or TM, focusing on the ST-35 and Ashi acupoint. The sessions took place over 4 weeks, three times a week, and were followed up over 8 weeks. The endpoint outcomes were separated into two categories, primary and secondary. The primary endpoint was assessed at the end of the 4-week treatment, using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. The secondary endpoint was evaluated at the end of the trial and consisted of the WOMAC function and stiffness score, visual analog pain [visual analog scale (VAS)] score, and 15-m walking time test. In addition, safety evaluation was performed throughout the trial. Results: Among the 92 randomized participants, 86 (93.48%) completed the trial; 43 in each group. The WOMAC pain score improved dramatically between the LM and TM groups, with a mean difference of 20.61 [95% confidence interval (CI): -2.28 to 43.50]. Given that the lower boundary of 95% CI was greater than -18.49, noninferiority was established. In addition, both LM and TM significantly decreased the WOMAC (pain, function and stiffness) score, VAS score (p < 0.05), and the 15-m walking time at the end of the trial. Interestingly, there were not significant differences between LM and TM (p > 0.05), suggesting that both are equally effective in treating KOA. Finally, among the 92 patients, 17 (18.48%) adverse effects were documented, namely 5 (10.87%) in the LM-treated group and 11 (26.09%) in the TM-treated group. Conclusions: 10.6 µm LM is not inferior to TM in treating KOA. Moreover, both LM and TM dramatically alleviated knee pain and enhanced function of knees. Clinical Trial Registration number: ISRCTN registry trial identifier: 14604492.

Electroacupuncture Attenuates Anxiety-Like Behaviors in a Rat Model of Post-traumatic Stress Disorder: The Role of the Ventromedial Prefrontal Cortex.

Electroacupuncture (EA) is a promising clinical approach to treating posttraumatic stress disorder (PTSD), yet the mechanisms whereby EA can alleviate anxiety and other PTSD symptoms have yet to be clarified. In the present report, rats underwent EA for 14 consecutive days following modified single prolonged stress (MSPS) exposure. These animals were then evaluated in open field and elevated plus maze tests (OFT and EPM), while Fos immunohistochemical staining was performed to assess ventromedial prefrontal cortex (vmPFC) functional activation. In addition, an extracellular recording and stimulation system was used to analyze vmPFC inputs into the ventral tegmental area (VTA) in these rats. Temporary vmPFC inactivation was further performed to assess whether this was sufficient to reverse the anxiolytic effects of EA. Overall, rats that underwent EA treatment spent more time in the central region (OFT) and the open arm (EPM) relative to MSPS model animals (P < 0.05). These MSPS model animals also exhibited significantly fewer activated Fos-positive nuclei in the vmPFC following behavioral testing, while EA was associated with a significant relative increase in c-Fos expression in this region. The transient inactivation of the vmPFC was sufficient to reverse the effects of EA treatment on anxiety-like behaviors in MSPS model rats. MSPS and SEA rats exhibiting no differences in bursting activity between baseline and vmPFC stimulation, whereas bursting activity rose relative to baseline upon ventral mPFC stimulation in EA treated and control rats. Together, these findings indicate that the vmPFC and its inputs into the VTA are functionally linked to the anxiolytic activity of EA, implicating this pathway in the EA-mediated treatment of PTSD.

Mechanosensitive TRPV4 Channel-Induced Extracellular ATP Accumulation at the Acupoint Mediates Acupuncture Analgesia of Ankle Arthritis in Rats.

(1) Background: Acupuncture (AP) is a safe and effective analgesic therapy. Understanding how fine needles trigger biological signals can help us optimize needling manipulation to improve its efficiency. Adenosine accumulation in treated acupoints is a vital related event. Here, we hypothesized that extracellular ATP (eATP) mobilization preceded adenosine accumulation, which involved local activation of mechanosensitive channels, especially TRPV4 protein. (2) Methods: AP was applied at the injured-side Zusanli acupoint (ST36) of acute ankle arthritis rats. Pain thresholds were assessed in injured-side hindpaws. eATP in microdialysate from the acupoints was determined by luminescence assay. (3) Results: AP analgesic effect was significantly suppressed by pre-injection of GdCl3 or ruthenium red in ST36, the wide-spectrum inhibitors of mechanosensitive channels, or by HC067047, a specific antagonist of TRPV4 channels. Microdialysate determination revealed a needling-induced transient eATP accumulation that was significantly decreased by pre-injection of HC067047. Additionally, preventing eATP hydrolysis by pre-injection of ARL67156, a non-specific inhibitor of ecto-ATPases, led to the increase in eATP levels and the abolishment of AP analgesic effect. (4) Conclusions: These observations indicate that needling-induced transient accumulation of eATP, due to the activation of mechanosensitive TRPV4 channels and the activities of ecto-ATPases, is involved in the trigger mechanism of AP analgesia.

[International communication system of acupuncture-moxibustion based on OSI model].

Borrowing the open system interconnection (OSI) model of internet protocol and the 5W theory in communication studies, the links in the international communication of acupuncture-moxibustion can be classified into seven layers: physical layer, data link layer, network layer, transport layer, session layer, presentation layer and application layer, therefore it is built an OSI model of international communication system of acupuncture-moxibustion. It is pointed out that present international communication system of acupuncture-moxibustion is similar to the user datagram protocol (UDP) in internet technology. Evidence-based medicine (EBM) plays a key role to modernize acupuncture- moxibustion theory based upon its clinical effects. According to phenomenon-taking by classified analogy, it is found that the PICO model of EBM agrees pretty well with the "three-way handshakes" mechanism of the internet transmission control protocol (TCP), which is promising to construct an international discourse of acupuncture-moxibustion compatible with western medicine. Thus it will benefit to explore the scientific connotation of acupuncture-moxibustion theory and significantly improve the international prestige of acupuncture-moxibustion.

Acupuncture modulates extracellular ATP levels in peripheral sensory nervous system during analgesia of ankle arthritis in rats.

As an ancient analgesia therapy, acupuncture has been practiced worldwide nowadays. A good understanding of its mechanisms will offer a promise for its rational and wider application. As the first station of pain sensation, peripheral sensory ganglia express pain-related P2X receptors that are involved in the acupuncture analgesia mechanisms transduction pathway. While the role of their endogenous ligand, extracellular ATP (eATP), remains less studied. This work attempted to clarify whether acupuncture modulated eATP levels in the peripheral sensory nerve system during its analgesia process. Male Sprague-Dawley rats underwent acute inflammatory pain by injecting Complete Freund's Adjuvant in the unilateral ankle joint for 2 days. A twenty-minute acupuncture was applied to ipsilateral Zusanli acupoint. Thermal hyperalgesia and tactile allodynia were assessed on bilateral hind paws to evaluate the analgesic effect. eATP of bilateral isolated lumbar 4-5 dorsal root ganglia (DRGs) and sciatic nerves were determined by luminescence assay. Nucleotidases NTPDase-2 and -3 in bilateral ganglia and sciatic nerves were measured by real-time PCR to explore eATP hydrolysis process. Our results revealed that acute inflammation induced bilateral thermal hyperalgesia and ipsilateral tactile allodynia, which were accompanied by increased eATP levels and higher mechano-sensitivity of bilateral DRGs and decreased eATP levels of bilateral sciatic nerves. Acupuncture exerted anti-nociception on bilateral hind paws, reversed the increased eATP and mechanosensitivity of bilateral DRGs, and restored the decreased eATP of bilateral sciatic nerves. NTPDase-2 and -3 in bilateral ganglia and sciatic nerves were inconsistently modulated during this period. These observations indicate that eATP metabolism of peripheral sensory nerve system was simultaneously regulated during acupuncture analgesia, which might open a new frontier for acupuncture research.