[Effects of moxibustion on serum levels of ß-EP, SP and expression of IL-1ß and COX-2 protein in brainstem in rats with migraine].

OBJECTIVE: To observe the effects of moxibustion at "Baihui" (GV 20) and "Dazhui" (GV 14) at different time points on the serum level of ß-endorphin (ß-EP), substance P (SP) and expression of interleukin-1ß (IL-1ß) and cyclooxygenase-2 (COX-2) protein in brainstem in rats with migraine, and to explore the effect and mechanism of moxibustion in preventing and treating migraine. METHODS: Forty male SD rats were randomly divided into a blank group, a model group, a prevention+treatment (PT) group and a treatment group, 10 rats in each group. Except the blank group, the rats in the remaining groups were injected with nitroglycerin subcutaneously to prepare migraine model. The rats in the PT group were treated with moxibustion 7 days before modeling (once a day) and 30 min after modeling, while the rats in the treatment group were treated with moxibustion 30 min after modeling. The "Baihui" (GV 20) and "Dazhui" (GV 14) were taken for 30 minutes each time. The behavioral scores in each group were observed before and after modeling. After intervention, ELISA method was used to detect the serum level of ß-EP and SP; the immunohistochemistry method was used to detect the number of positive cells of IL-1ß in brainstem; the Western blot method was used to detect the expression of COX-2 protein in brainstem. RESULTS: Compared with the blank group, the behavioral scores in the model group were increased 0-30 min, 60-90 min and 90-120 min after modeling (P<0.01); compared with the model group, in the treatment group and the PT group, the behavioral scores were decreased 60-90 min and 90-120 min after modeling (P<0.01). Compared with the blank group, in the model group, the serum level of ß-EP was decreased (P<0.01), while the serum level of SP, the number of positive cells of IL-1ß in brainstem and the expression of COX-2 protein were increased (P<0.01). Compared with the model group, in the PT group and and the treatment group, the serum level of ß-EP was increased (P<0.01), while the serum level of SP, the number of positive cells of IL-1ß and the expression of COX-2 protein in brainstem were decreased (P<0.01, P<0.05). Compared with the treatment group, in the PT group, the serum level of ß-EP was increased and COX-2 protein expression was decreased (P<0.05). CONCLUSION: Moxibustion could effectively relieve migraine. The mechanism may be related to reduce the serum level of SP, IL-1ß and COX-2 protein expression in brainstem, and increase the serum level of ß-EP, and the optimal effect is observed in the PT group.

[Effect of electroacupuncture on pain threshold and expression of pain-related factors cyclooxygenase-2, prostaglandin E2 and ß-endorphin in rats with chronic pelvic pain syndrome].

OBJECTIVE: To explore the possible mechanism of electroacupuncture (EA) underlying improvement of chronic pelvic pain syndrome (CPPS). METHODS: Fifty SD rats were randomly divided into control, model, sham operation, EA and sham EA groups (n=10 rats in each group). The CPPS model was established by injecting complete Freund's adjuvant (CFA, 50 µL) into the ventral lobes of the prostate. EA (2 Hz/100 Hz) was applied to "Guanyuan"(CV4), "Zhongji"(CV3), "Sanyinjiao" (SP6) and "Huiyang"(BL35) once daily for 40 min, 5 days a week for 4 weeks, while rats in the sham EA group were treated with the same acupoints but without electrical stimulation. Mechanical pain threshold (MPT) and heat pain threshold (HPT) were measured before and after intervention. The body weight and prostate weight were measured and prostate index was calculated. Histopathological changes of prostate tissue were observed by HE staining. The levels of cycloxygenase-2 (COX-2), prostaglandin E2 (PGE2) and ß-endorphin (ß-EP) in prostate tissue were detected by ELISA. RESULTS: Compared with the control and sham operation groups, the MPT and HPT were significantly lower (P<0.01), and the prostate weight, prostate index, the contents of PGE2 and COX-2 were significantly increased (P<0.01), while the content of ß-EP was significantly decreased (P<0.01) in the model group. Compared with the model group, the MPT and HPT were significantly increased (P<0.01) after 3 and 4 courses of treatment, and the prostate weight, prostate index, the contents of PGE2 and COX-2 were significantly decreased (P<0.01), while the content of ß-EP was significantly increased (P<0.01) in the EA group, rather than in the sham EA group (P>0.05). CONCLUSION: EA can effectively relieve pain in CPPS rats, which may be related to its functions in down-regulating COX-2 and PGE2, and up-regulating ß-EP.

[Research progress of neuroendocrine mechanism of acupuncture for dyspnea].

The paper reviewed the relevant studies on dyspnea treated with acupuncture over the past 20 years, as well as the underlying neuroendocrine mechanism from the perspective of central and peripheral vagus nerves, neurotransmitter, respiratory muscle function and anti-depression-anxiety function. It revealed that the central response area was regulated by acupuncture in treatment of dyspnea, which is similar to the area affected in acupuncture analgesia. Additionally, acupuncture generates its therapeutic effects on dyspnea through promoting the release of endogenous opioid peptides and the regulation of autonomic nerve, amygdale and hypothalamic-pituitary-adrenal axis.

The effects of conventional, warm and cold acupressure on the pain perceptions and beta-endorphin plasma levels of primiparous women in labor: A randomized controlled trial.

OBJECTIVE: This study was performed to determine the impact of different acupressure procedures, performed on women's hands during labor, on ß-endorphin plasma levels and labor pain perception. DESIGN: Randomized controlled experimental trial SETTING AND PARTICIPANTS: This study was conducted with 140 pregnant women in the delivery rooms of a university research and training hospital and a state hospital in a province in the Black Sea Region of Turkey. METHODS: This study was conducted with three experimental groups (who had conventional, warm and cold acupressure on their LI4 acupressure point) and one control group (no acupressure). Each group included 35 pregnant women. The data were collected using a personal information form, the Labor Intervention Follow-up Form, the Visual Analog Scale (VAS) and the Verbal Category Scale (VCS). Its main outcomes were the women's labor pain perceptions and ß-endorphin plasma levels. RESULTS: The experimental and control groups had homogeneous introductory characteristics. The experimental groups had significantly higher mean VAS and VCS posttest scores than the control group (p<0.001). The experimental groups' mean posttest ß-endorphin plasma levels were also significantly higher (p<0.05). CONCLUSION: In this study, conventional, warm and cold acupressure reduced the women's labor pain and increased their ß-endorphin plasma levels. Midwives can use acupressure to reduce labor pain.

Β-endorphin-immunoreactive perikarya appear to receive innervation from NPY-immunoreactive fiber varicosities in the human hypothalamus.

Morphological and pharmacological studies indicate that hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons communicate with each other in rats and regulate a variety of hypothalamic and extrahypothalamic functions. Indeed, electron microscopic studies revealed NPY-immunoreactive (NPI-IR) synapses on ß-endorphin-IR neurons in the hypothalamus. However, no such connections have been reported in humans. Here, we studied the putative NPY-ß-endorphin associations with high-resolution light microscopic double-label immunocytochemistry in the human hypothalamus. The majority of ß-endorphin-IR perikarya appear to be innervated by abutting NPY-IR fibers in the infundibulum/median eminence, receiving more than 6 contacts (38% of the counted neurons) or three to six contacts (42% of the counted neurons). The rest of the ß-endorphin-IR neurons are lightly innervated by NPY fibers (14%, one-three contacts) or do not receive any detectable NPY-IR axon varicosities (6% of the counted neurons). Since ß-endorphin is cleaved from the proopiomelanocortin (POMC) precursor, the NPY-ß-endorphin connections also provide the foundation for NPY-α-MSH and NPY-ACTH connections and their subsequent physiology. The close anatomical connections between NPY-IR nerve terminals and ß-endorphin-IR neurons reported herein may represent functional synapses and provide the foundation for NPY-stimulated ß-endorphin release. By interacting with ß-endorphin, NPY may have a more widespread regulatory capacity than acting alone on different neurotransmitter systems.

Effects of electroacupuncture on pain sensation in a rat model of hyperalgesia with nicotine dependence.

Tobacco smoking is considered to be one of the main risk factors in the development of chronic pain. Long-term chronic exposure to nicotine and other forms of tobacco have been shown to be associated with an increased incidence of pain. Studies have shown that acupuncture can help smokers to reduce their desire to smoke, reduce their withdrawal symptoms, and avoid a relapse after treatment. However, little has been reported about the effects of acupuncture on pain sensitivity caused by long-term smoking. Models of hyperalgesia were established in rats exposed to nicotine for 6 weeks. After 6 weeks of continuous nicotine exposure, electroacupuncture at bilateral acupoints Zusanli (ST36) and Taichong (LR3) was performed 20 minutes per day for 6 days at a continuous wave with a frequency of 2 Hz and a stimulus intensity of 1 mA. The results revealed that electroacupuncture treatment increased the mechanical response threshold of hind paw of nicotine-dependent rats with hyperalgesia and up-regulated the protein expression of pain-related factors µ-opioid receptor, ß-endorphin and glutamic acid decarboxylase 65 in the spinal cord and midbrain periaqueductal gray and the protein expression of glutamic acid decarboxylase 67 in the spinal cord. These findings suggest that electroacupuncture treatment has positive analgesic effects on pain sensitivity caused by long-term chronic nicotine exposure. One possible mechanism for the improved analgesia is that electroacupuncture increases the expression of pain-related factors in the spinal cord and midbrain periaqueductal gray. This study was approved by Institutional Animal Care and Use Committee (IACUC) of the University of Miami (#18-167) on December 12, 2018.

The Effect of Electroacupuncture Therapy on Pain, Plasma ß-Endorphin, and Quality of Life of Stage III Cervical Cancer Patients: A Randomized Control Trial.

Background: Pain is a major complaint in cancer patients and a global problem that requires medical attention, including pain in cervical cancer. Although pharmacotherapy has been used for the treatment of cancer pain, there are still around 40% cannot be treated only with pharmacotherapy. Objectives: To determine the effects of electroacupuncture (EA) on pain in stage III cervical cancer patients. Methods: Twenty-eight stage III cervical cancer patients were divided into two groups (14 treatments and 14 controls) with randomized control trial design. The treatment group received EA with a frequency of 2/20-25 Hz at points of ST36, SP6, LI4 and LR3 for 30 minutes, while the control group did not receive EA. Both groups were given paracetamol and codeine at the same dose. Assessment was carried out by measuring pain scale (VAS), plasma ß-endorphin levels, and quality of life/QoL (EORTC QLQ-C30) before and after therapy. Results: The average reduction in VAS in the treatment group (2.71 ± 1.14) compared to the control group (0.71 ± 1.33; p < 0.001), average increase in plasma ß-endorphin levels in the treatment group (88.57 ± 52.46 pg/ml) compared to the control group (12.86 ± 56.76 pg/ml; p = 0.001), and in QoL, there were significant differences in symptom improvement between the treatment and control groups in the domain of fatigue, pain, insomnia and overall QoL (p < 0.05). Conclusion: Medical therapy combined with EA decreased pain scale, increased plasma ß-endorphin levels, and improved the QoL for stage III cervical cancer patients.

Electroacupuncture Versus Analgesics for Patients with Stage IIIB Cervical Cancer Post Cisplatin Chemotherapy.

Background: The prevalence of pain at advanced cervical cancer stages is increasing. Existing World Health Organization recommendations for management comprises a 3-step ladder of analgesic therapy but this still cannot address this pain optimally. An alternative therapy used to reduce pain, acupuncture, is almost without side-effects, is safe, and is easy to implement. This study compared electroacupuncture (EA) versus paracetamol 500 mg +10-mg codeine therapy for patients with stage-IIIB cervical cancer post cisplatin chemotherapy. Materials and Methods: Participants were divided into 2 groups (treatment and control groups). A quasiexperimental study was conducted using a nonequivalent control group pretest-post-test design. Participants in the treatment group were given EA for 30 minutes 10 times over 3 weeks, while participants in the control group were given paracetamol 3 × 500 mg and codeine 3 × 10 mg orally every day for 3 weeks. Statistical analysis used paired t-tests, a Wilcoxon test, an independent t-test, or a Mann-Whitney-U test with P < 0.05. Results: Pretest and post-test pain-scale levels were 5.39 ± 0.62 and 4.57 ± 0.88, respectively (P < 0.001). Average endorphin-ß levels at pretest and post-test were 571.80 ± 281.13 and 491.14 ± 272.14, respectively (P = 0.818). Median values of quality of life at pretest and post-test were 681.75 (range: 503.80-915.20) and 635.25 (range: 538.20-781.20; P = 0.383), respectively. Conclusions: Pain-control therapy using drugs or EA produces similar results. However, EA, subjectively, produces improved pain-scale results better than pharmaceuticals.

Glycyl-l-glutamine attenuates NPY-induced hyperphagia via the melanocortin system.

This study aimed to determine whether glycyl-l-glutamine (Gly-Gln; ß-endorphin (30-31)), a non-opioid peptide derived from ß-endorphin processing, modulates neuropeptide Y (NPY)-induced feeding and hypothalamic mRNA expression of peptide hormones in male broiler chicks. Intracerebroventricular injection of NPY (235 pmol) generated a hyperphagic response in ad libitum chicks within 30 min. Co-administration of Gly-Gln (100 nmol) attenuated this response, inducing a 30 % decrease. This was not attributable to Gly-Gln hydrolysis because co-administration of glycine (Gly) and glutamine (Gln) had no effect on NPY-induced hyperphagia. Gly-Gln injected alone also showed no effect. The hypothalamic pro-opiomelanocortin mRNA expression in the co-injection group was significantly higher than that in the NPY alone group. These data indicate that endogenous Gly-Gln may contribute to regulate feeding behavior via the central melanocortin system in chicks and acts as a counter regulator of the neural activity in energy metabolism.

The GLP-1 receptor herbal agonist morroniside attenuates neuropathic pain via spinal microglial expression of IL-10 and ß-endorphin.

OBJECTIVES: To assess the protective effect of the glucagon-like peptide-1 receptor (GLP-1R) agonist morroniside against neuropathic pain and its downstream mechanisms of activating microglial GLP-1R/interleukin-10 (IL-10)/ß-endorphin antinociceptive pathway. METHODS: Spinal nerve ligation-induced neuropathic pain rats were intrathecally injected with morroniside, with mechanical paw withdrawal threshold being assessed. The expression of spinal and cultured microglia IL-10 and ß-endorphin were detected with qRT-PCR. KEY FINDINGS: Morroniside alleviated mechanical allodynia in neuropathic rats, which was blocked by inhibiting or depleting microglia. In addition, neutralizing spinal IL-10 or ß-endorphin with specialized antibodies or blocking the µ-opioid receptor was able to fully reverse the morroniside-induced mechanical antiallodynia. Morroniside treatment stimulated the gene expression of IL-10 and ß-endorphin in the spinal lumbar enlargements of neuropathic rats as well as in primary cultured microglia. Furthermore, pretreatment with the IL-10 antibody blocked morroniside-stimulated ß-endorphin expression in the spinal cords of neuropathic rats and cultured primary microglia, whereas the ß-endorphin antibody failed to affect morroniside-stimulated gene expression of IL-10. CONCLUSIONS: These results reveal that morroniside produces therapeutic effects in neuropathy through spinal microglial expression of IL-10 and subsequent ß-endorphin after activation of GLP-1R.

Different Processed Products of Curcumae Radix Regulate Pain-Related Substances in a Rat Model of Qi Stagnation and Blood Stasis.

BACKGROUND: Curcumae blood Radix (Yujin) has been widely used to treat Qi stagnation and stasis in TCM. According to the Chinese Pharmacopoeia, the tuberous roots of Curcuma longed L. (i.e., Huangsiyujin, HSYJ) is one of the major species of Yujin. According to the processing theory of TCM, stir-frying HSYJ with vinegar might strengthen the effect of dispersing stagnated hepatoqi to relieve pain, and stir-frying HSYJ with wine might strengthen the effect of promoting blood circulation in order to remove blood stasis. However, the mechanism for the enhancement of clinical efficacy by processing is unclear. AIM/HYPOTHESIS: This study was aimed at evaluating the effect of different processed products of HSYJ on chemical constituents and pain-related substances to explore underlying mechanisms of HSYJ in treating pain caused by Qi stagnation and blood stasis. METHODS: The effects of different processing methods on the paste yield of water decoction were analyzed, and the content of the main constituents were detected by HPLC. A rat model of Qi stagnation and blood stasis was established by tail clamp stimulation combined with subcutaneous adrenaline injection. After treatment and intervention with HSYJ and its processed products, ß-endorphin (ß-EP) and 5-hydroxytryptamine (5-HT) were measured by ELISA, and the expression of c-fos was evaluated by immunohistochemistry. RESULTS: After stir-frying with vinegar or wine, the extract yield and curcumin content increased. Compared with model group, raw HSYJ could significantly improve the abnormality of 5-HT in plasma (P < 0.05) and ß-EP in brain (P < 0.01). Stir-frying HSYJ with vinegar or wine could significantly improve the abnormality of 5-HT in plasma, ß-EP in brain, and the expression of c-fos (P < 0.01). Stir-frying HSYJ with vinegar could also significantly increase the level of ß-EP in plasma (P < 0.05). CONCLUSION: These results showed that different processing methods have certain effects on the chemical constituents of HSYJ, mainly in increasing the decoction rate and curcumin content. HSYJ and its processed products can reduce 5-HT levels, increase ß-EP levels, and inhibit the expression of c-fos in model rats. The effects of stir-frying HSYJ with vinegar on ß-EP levels in plasma was superior to others.

Low frequency electroacupuncture alleviates neuropathic pain by activation of spinal microglial IL-10/ß-endorphin pathway.

Electroacupuncture produces analgesia in chronic pain patients and animal models of pain hypersensitivity. The current study aims to illustrate the mechanisms underlying electroacupuncture-attenuated neuropathic pain. Neuropathic rats, induced by tight ligation of L5/L6 spinal nerves, markedly reduced mechanical thresholds in the ipsilateral hindpaws relative to the contralateral hindpaws. Low frequency (2 Hz) electroacupuncture stimulation for a period of 20 min alleviated neuropathic pain in the ipsilateral hindpaws of neuropathic rats in a time-dependent manner. The same electroacupuncture treatment also stimulated spinal gene and protein expression of IL-10 and ß-endorphin but not dynorphin A, measured by real-time quantitative PCR and ELISA kits. Intrathecal injection of the specific IL-10 antibody in neuropathic rats completely blocked electroacupuncture-increased spinal expression of ß-endorphin, but the ß-endorphin antibody failed to alter electroacupuncture-stimulated spinal IL-10 expression. Using a double fluorescence immunostaining technique, we observed that electroacupuncture stimulated spinal IL-10 and ß-endorphin expression in microglia but not in neurons or astrocytes in the spinal dorsal horn of neuropathic rats. Pretreatment with intrathecal injection of the microglial inhibitor minocycline, specific IL-10 antibody and ß-endorphin antiserum (but not the dynorphin A antibody), or selective µ-opioid receptor antagonist CTAP (but not κ- or δ-opioid receptor antagonist) completely blocked electroacupuncture-induced attenuation of neuropathic pain. These results suggest that low frequency electroacupuncture alleviates neuropathic pain through stimulation of the spinal microglial expression of IL-10 and subsequent expression of ß-endorphin.

Pain Relief Dependent on IL-17-CD4+ T Cell-ß-Endorphin Axis in Rat Model of Brachial Plexus Root Avulsion After Electroacupuncture Therapy.

BACKGROUND AND PURPOSE: Neuropathic pain is the typical symptom of brachial plexus root avulsion (BPRA), and no effective therapy is currently available. Electroacupuncture (EA), as a complementary and alternative therapy, plays a critical role in the management of pain-associated diseases. In the present study, we aimed to reveal the peripheral immunological mechanism of EA in relieving the pain of BPRA through the IL-17-CD4+ T lymphocyte-ß-endorphin axis. METHODS: After receiving repeated EA treatment, the pain of BPRA in rats along with the expressions of a range of neurotransmitters, the contents of inflammatory cytokines, and the population of lymphocytes associated were investigated. CD4+ T lymphocytes were either isolated or depleted with anti-CD4 monoclonal antibody. The titers of IL-17A, interferon-γ (IFN-γ), and ß-endorphin were examined. The markers of T lymphocytes, myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), macrophages, and natural killer (NK) cells were assessed. The activation of the nuclear transcription factor κB (NF-κB) signaling pathway was tested. RESULTS: The pain of BPRA was significantly relieved, and the amount of CD4+ T lymphocytes was increased after EA treatment. The release of ß-endorphin was up-regulated with the up-regulation of IL-17A in CD4+ T lymphocytes. The titer of IL-17A was enhanced, leading to an activated NF-κB signaling pathway. The release of ß-endorphin and the analgesic effect were almost completely abolished when CD4+ T lymphocytes were depleted. CONCLUSION: We, for the first time, showed that the neuropathic pain caused by BPRA was effectively relieved by EA treatment via IL-17-CD4+ T lymphocyte-ß-endorphin mediated peripheral analgesic effect, providing scientific support for EA clinical application.

[Effect of combined acupuncture-medicine anesthesia in thyroid nodule ablation and its effect on serum ß-endorphin].

OBJECTIVE: To investigate the anesthetic effect of combined acupuncture-medicine anesthesia in microwave ablation of benign thyroid nodules and its effect on serum ß-endorphin. METHODS: A total of 60 patients who met the inclusion criteria and received microwave ablation of benign thyroid nodules were randomly divided into the treatment group and the control group, with 30 patients in each. The patients in the treatment group were given combined acupuncture-medicine anesthesia, and those in the control group were given intravenous anesthesia. The two groups were compared in terms of the sedative and analgesic effects of anesthesia, amount of anesthetics used, incidence rate of intraoperative snore and respiratory depression, and change in serum ß-endorphin level before anesthesia, before surgery, and after the surgery. RESULTS: Both groups obtained satisfactory anesthetic effects. Compared with the control group, the sedation score, the amounts of fentanyl and propofol used, the incidence rates of intraoperative snore and respiratory depression in the treatment group were obviously lower (P<0.05, P<0.01). The treatment group had an increase in serum ß-endorphin level before surgery and at the end of surgery (P<0.05), while the control group showed no significant change in serum ß-endorphin level at each time point. CONCLUSION: In microwave ablation of benign thyroid nodules, combined acupuncture-medicine anesthesia has good sedative and analgesic effects and can reduce the amounts of anesthetics used as well as the incidence rates of intraoperative snore and respiratory depression. The analgesic effect of acupuncture anesthesia is associated with increased ß-endorphin secretion.

Physiological persona differences based on stress and inflammation between meditators and healthy controls.

Background Nowadays, yoga is endorsed and advised routinely to stay fit and healthy, as well as control many chronic diseases including diabetes type 2, hypertension, coronary artery diseases, etc. Now, our assumption is that those who do regular yoga have different persona than who do not do yoga regularly. We planned to test our hypothesis scientifically, and therefore baseline physiological characteristics with stress and inflammation levels in long-term and short-term meditators and healthy novice controls were analyzed. Methods In this retrospective analysis, 97 male participants were included for their Baseline analysis. Fifteen apparently healthy subjects practicing preksha meditation (since >5 years, at least 5 days a week) were included as long-term meditators (LTMs); 58 subjects who attended one of our short-term yoga-based lifestyle intervention programs for 2 weeks were included as short-term meditators (STMs); 24 male novice subjects, who did not participate in any yogic intervention, were included as healthy controls. Here, we analyzed the Baseline plasma levels of stress and inflammatory markers, cortisol, ß-endorphin, interleukin (IL)-6 and tumor necrosis factor (TNF)-α in long-term meditators vs. short-term meditators vs. healthy controls. Outcome measures The study parameters body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), plasma levels of stress and immune markers, cortisol, ß-endorphin (ß-Ed), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were assessed in all the three groups at baseline. Results Significant (p<0.05) differences were observed at baseline for plasma levels of stress and inflammatory markers as well as body mass index and systolic blood pressure among LTM vs. STM vs. healthy controls. Conclusions Our observations suggest that the subjects who do regular yoga-meditation practice have better stress & inflammation status than comparable age matched healthy controls.

[Effect of electroacupunture on supplementary analgesia and the levels of serum ß-endorphin and prostaglandin E2 in patients with total knee arthroplasty].

OBJECTIVE: To observe the effect on supplementary analgesia after total knee arthroplasty (TKA) treated with electroacupunture, and explore it's mechanism. METHODS: A total of 40 patients with severe knee osteoarthritis were randomized into an observation group and a control group, 20 cases in each one. During the operation, patients were given epidural anesthesia in the two groups, conventional patient controlled epidural analgesia and oral celecoxib were applied after the operation. In the observation group, electroacupunture was used at Liangqiu (ST 34), Xuehai (SP 10), Yinlingquan (SP 9), Zusanli (ST 36), Fenglong (ST 40) and Qiuxu (GB 40) on the operation side from the 1st to 7th day after the operation to support analgesia, 30 min for each time, once a day. The visual analogue scale (VAS) was used to record postoperative pain of resting state and active state. The levels of serum prostaglandin E2 and ß-endorphin were measured on the 1st and 7th day after surgery in the two groups. RESULTS: In the observation group, the VAS scores of resting state and active state were superior to the control group on the 3rd, 5th and 7th day after the operaton (all P<0.05); after the treatment, the level of serum ß-endorphin was increased and the level of serum prostaglandin E2 was reduced in the two groups (all P<0.05), and the change of the observation group was larger than that of the control group (both P<0.05). CONCLUSION: Electroacupunture has the effect of supplementary analgesia for patients after TKA, the mechanism may be related to promote the synthesis of ß-endorphin and inhibit the synthesis of prostaglandin E2.

[Warming Needle Moxibustion Relieves Symptoms of Lumbar Disc Herniation Patients and Upregulates Plasma ß-endorphin].

OBJECTIVE: To analyze the effect of warming needle moxibustion of Jiaji (EX-B 2), Huantiao (GB 30), etc. on lumbago and other symptoms of lumbar disc herniation (LDH) patients and changes of plasma ß-endorphin (ß-EP) content. METHODS: A total of 60 LDH patients were equally randomized into warming needle moxibustion group and conventional acupuncture group. Patients of the conventional acupuncture group were treated by puncturing lumbar Jiaji (EX-B 2), Huantiao (GB 30), Weizhong (BL 40), and Yanglingquan (GB 34) with filiform acupuncture needles. Patients of the warming needle moxibustion group were treated by puncturing the same 4 acupoints, and with the acupuncture needle in lumbar EX-B 2 attached an ignited moxa-stick segment. The treatment in both groups lasted for 30 min every time, once every other day for 15 times, with 5 times being a therapeutic course and two days' rest between every two courses. The therapeutic effect was evaluated according to the "Criteria for Evaluating the Therapeutic Effect of Disorders of Traditional Chinese Medicine". The lumbago severity was assessed using visual analogue scale (VAS), and the lumbar functional activity assessed using modified Oswestry dysfunction (in objects-lifting, sitting, standing, walking, sleeping, pain, activity of daily living, social activity, outing, etc.) index (ODI). The plasma ß-EP content was assayed using ELISA. RESULTS: After the treatment, of the two 30 cases in the conventional acupuncture and warming needle moxibustion groups, 8 (26.67%) and 12 (40.00%) were under control, 8 (26.67%) and 10 (33.33%) had a marked improvement, 3 (10.00%) and 4 (13.33%) were effective, and 11 (36.66%) and 4 (13.33%) ineffective, with the effective rates being 63.34% and 86.66%, respectively. The effective rate of the warming needle moxibustion was significantly higher than that of the conventional acupuncture (P<0.05). The VAS scores and ODI values of the two groups were gradually decreased along with the prolongation of treatment, and significantly lower in the warming needle moxibustion group than in the acupuncture group at the 1st, 2nd and 3rd course of treatment (P<0.01). The levels of plasma ß-EP were gradually increased in the two groups at the 1st, 2nd and 3rd course of treatment, and were obviously higher in the warming needle moxibustion group than in the conventional acupuncture group at each of the 3 courses (P<0.01). No obvious adverse reactions were observed in the two groups. CONCLUSION: Warming needle moxibustion has a better therapeutic effect in relieving lumbago and lumbar dysfunction, and can up-regulate blood ß-EP level.

Pain Relief with Wet Cupping Therapy in Rats is Mediated by Heat Shock Protein 70 and ß-Endorphin.

BACKGROUND: Wet cupping therapy is a complementary therapy in pain management. The mechanism of this therapy, however, needs further elucidation. Cells injured by wet cupping therapy seem to stimulate the expression of heat shock protein 70 (HSP70). Its benefit in pain reduction could be mediated by the expression of ß-endorphin. This study aimed at determining the correlation between HSP70 and ß-endorphin after wet cupping therapy. METHODS: Sixteen male Wistar rats were divided into control (CG; n=8) and treatment (TG; n=8) groups. The rats in both groups were injected with complete Freund's adjuvant (CFA) at the footpad. In the TG, wet cupping therapy was done at the left and right paralumbar regions 48 hours after the CFA injection. Twenty-four hours after therapy, the hot plate test was done to assess pain threshold. Thereafter, immunohistochemistry from the skin subjected to wet cupping therapy was conducted for HSP70 and ß-endorphin. RESULTS: The expression of HSP70 was significantly higher in the keratinocytes of the TG (20.25±3.53; P<0.001) than in the keratinocytes of the CG (10.50±2.44; P<0.001). The expression of ß-endorphin was significantly higher in the keratinocytes of the TG (22.37±3.52; P<0.001) than in the keratinocytes of the CG (5.12±1.72; P<0.001). The results also revealed a high correlation between HSP70 and ß-endorphin (ß=0.864; P<0.001). Pain threshold after wet cupping therapy was significantly higher in the TG (22.81±6.34 s; P=0.003) than in the CG (11.78±3.56 s). CONCLUSIONS: The benefit of wet cupping therapy in terms of pain reduction in rats could be mediated by the expression of HSP70 and ß-endorphin.

Diosmin, a Citrus Nutrient, Activates Imidazoline Receptors to Alleviate Blood Glucose and Lipids in Type 1-Like Diabetic Rats.

Diosmin is a nutrient that is widely contained in citrus and that has been indicated to improve glucose metabolism in diabetic disorders. Recently, we demonstrated that diosmin induces ß-endorphin to lower hyperglycemia in diabetic rats. However, the mechanisms of diosmin in opioid secretion were unclear. Therefore, we focused on the secretion of opioids from isolated adrenal glands induced by diosmin. The changes in the released ß-endorphin-like immunoreactivity (BER) were determined using ELISA. Diosmin increased the BER level in a dose-dependent manner, and this effect was markedly reduced in the absence of calcium ions. Activation of the imidazoline I-2 receptor (I-2R) has been introduced to induce opioid secretion. Interestingly, we observed that diosmin activates CHO cells expressing I-R. Additionally, diosmin-increased BER was inhibited by the blockade of I-2R in isolated adrenal glands. Additionally, an antagonist of I-2R blocked diosmin-induced effects, including the reduction in hyperglycemia and the increase in plasma BER in streptozotocin-induced diabetic rats (STZ-diabetic rats). Repeated treatment of STZ-diabetic rats with diosmin for one week induced changes in hepatic glycogen, lipid levels, and the expression of phosphoenolpyruvate carboxykinase (PEPCK). Furthermore, an antagonist of I-2R blocked the diosmin-induced changes. Additionally, plasma lipids modified by diosmin were also reversed by the blockade of I-2R in STZ-diabetic rats. Taken together, we suggest that diosmin may activate I-2R to enhance the secretion of ß-endorphin from adrenal glands and to influence metabolic homeostasis, resulting in alleviation of blood glucose and lipids in STZ-diabetic rats.

Antihyperglycaemic action of diosmin, a citrus flavonoid, is induced through endogenous ß-endorphin in type I-like diabetic rats.

Diosmin is one of the flavonoids contained in citrus and has been demonstrated to improve glucose metabolism in diabetic disorders. However, the mechanism(s) of diosmin in glucose regulation remain obscure. Therefore, we investigated the potential mechanism(s) for the antihyperglycaemic action of diosmin in streptozotocin-induced diabetic rats (STZ-diabetic rats). Diosmin lowered hyperglycaemia in a dose-dependent manner in STZ-diabetic rats. This action was inhibited by naloxone at a dose sufficient to block opioid receptors. Additionally, we determined the changes in plasma ß-endorphin-like immunoreactivity (BER) using enzyme-linked immunosorbent assay (ELISA). Diosmin also increased BER dose-dependently in the same manner. Repeated treatment of STZ-diabetic rats with diosmin for 1 week resulted in an increase in the expression of the glucose transporter subtype 4 (GLUT 4) in the soleus muscle and a reduction in the expression of phosphoenolpyruvate carboxykinase (PEPCK) in the liver. These effects were also inhibited by naloxone at a dose sufficient to block opioid receptors. Bilateral adrenalectomy in STZ-diabetic rats eliminated the actions of diosmin, including both the reduction in hyperglycemia and the elevation of plasma BER. In conclusion, our results suggest that diosmin may act on the adrenal glands to enhance the secretion of ß-endorphin, which can stimulate the opioid receptors to attenuate hepatic gluconeogenesis and increase glucose uptake in soleus muscle, resulting in reduced hyperglycemia in STZ-diabetic rats.