Effect of transcutaneous electrical acupoint stimulation on remifentanil dosage during craniotomy aneurysm clipping: a prospective, randomized controlled study.

BACKGROUND: Craniotomy aneurysm clipping is one of the main treatments for intracranial aneurysm (IA). Endotracheal intubation and intraoperative operation may induce dramatic hemodynamic fluctuations and increase the risk of aneurysm rupture. Intraoperative high-dose opioid use is the main measure to reduce the intraoperative stress response, but it increases the incidence of complications such as postoperative vomiting and delayed awakening. Transcutaneous electrical acupoint stimulation (TEAS) stimulates ß-endorphin expression levels and reduces opioid requirements. In this study, we aimed to assess the effects of TEAS on remifentanil dosage and oxidative stress (OS) in craniotomy aneurysm clipping. METHOD: Forty-two patients with craniotomy aneurysm clipping were randomized into two groups: the TEAS group (T group) and the sham TEAS group (S group). "Hegu" (LI4), "Neiguan" (PC6) and "Zusanli" points (ST36) were selected, and a "HANS" percutaneous acupoint electrical stimulator was used for intervention 30 min before anesthesia induction until the end of the operation. The primary outcome was intraoperative remifentanil dosage. The secondary outcomes were intraoperative propofol dosage, mean arterial pressure (MAP) and heart rate (HR) 5 min before the TEAS intervention (T0), 5 min before head holder pinning (T1), immediately after pinning (T2), 5 min before craniotomy (T3), immediately after craniotomy (T4), at craniotomy (T5), and at the end of surgery (T6), as well as serum ß-endorphin levels at T1, T2 and T6 and neuron-specific enolase (NSE), S100ß, superoxide dismutase (SOD) and malondialdehyde (MDA) levels at T1, T2 and 24 h after surgery (T7). RESULTS: The dosage of remifentanil in the T group was reduced compared to that in the S group (P < 0.05). At T2, T4 and T5, the MAP and HR in the T group were lower than those in the S group (P < 0.05). At T2 and T7, the levels of NSE, S100ß and MDA in group T were lower than those in group S (P < 0.05), while the SOD levels in group T were higher than those in group S (P < 0.05). CONCLUSIONS: The use of TEAS can reduce the dosage of remifentanil and reduce hemodynamic fluctuations during craniotomy aneurysm clipping. It reduces the occurrence of OS and central nervous system damage during surgery and has a certain brain protective effect. TRIAL REGISTRATION: ChiCTR2100052353. https://www.chictr.org.cn/about.html .

Curative effect of wrist-ankle acupuncture on postpartum abdominal pain and its influence on serum ß-EP level in puerpera. / è •è¸é’ˆæ²»ç–—äº§åŽè ¹ç—›çš„ä¸´åºŠç–—æ•ˆåŠå¯¹äº§å¦‡è¡€æ¸ ß-EP水平的影响.

OBJECTIVES: To observe the clinical effect of wrist-ankle acupuncture on postpartum abdominal pain and its influence on serum beta-endorphin (ß-EP) level in puerpera. METHODS: Seventy patients with postpartum abdominal pain were randomly divided into an acupuncture + herbal medication group (35 cases, 1 case dropped out) and a herbal medication group (35 cases, 2 cases dropped out). In the herbal medication group, 1 day after delivery, modified shenghua decoction was taken orally, one dose a day. In the acupuncture + herbal medication group, on the basis of herbal medication, wrist-ankle acupuncture was given at the Lower 1 and Lower 2 of the ankles, once daily. The duration of treatment was 3 days in the two groups. Before and after treatment, the score of visual analogue scale (VAS) for pain, serum ß-EP level, uterine fundus height, postpartum conditions of lochia and the uterine recovery at 42 days postpartum were compared in the patients of the two groups. RESULTS: At each time point after treatment (24 h, 48 h and 72 h after delivery), VAS scores and the uterine fundus height were reduced as compared with those before treatment (2 h after delivery) in the two groups (P<0.05); these indexes in the acupuncture + herbal medication group were lower than those in the herbal medication group (P<0.05). After treatment (72 h after delivery), ß-EP levels in the serum were increased when compared with those before treatment in the two groups (P<0.05), and the ß-EP level in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05). The volume of postpartum lochia discharge in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05), while the duration of postpartum lochia discharge and the total time of lochia discharge were shorter (P<0.05). Regarding the recovery of the uterus at 42 days postpartum, there was no statistical significance between the two groups (P>0.05). CONCLUSIONS: Wrist-ankle acupuncture obviously reduces the degree of postpartum abdominal pain and promotes the lochia discharge and the uterine recovery. The effect mechanism may be related to the up-regulation of serum ß-EP level and the increase of pain threshold so that analgesia is obtained.

Local analgesia of electroacupuncture is mediated by the recruitment of neutrophils and released ß-endorphins.

ABSTRACT: The efficacy of acupuncture in treating pain diseases has been recognized in clinical practice, and its mechanism of action has been a hot topic in academic acupuncture research. Previous basic research on acupuncture analgesia has focused mostly on the nervous system, with few studies addressing the immune system as a potential pathway of acupuncture analgesia. In this study, we investigated the effect of electroacupuncture (EA) on the ß-endorphins (ß-END) content, END-containing leukocyte type and number, sympathetic neurotransmitter norepinephrine (NE), and chemokine gene expression in inflamed tissues. To induce inflammatory pain, about 200 µL of complete Frester adjuvant (CFA) was injected into the unilateral medial femoral muscle of adult Wistar rats. Electroacupuncture treatment was performed for 3 days beginning on day 4 after CFA injection, with parameters of 2/100 Hz, 2 mA, and 30 minutes per treatment. The weight-bearing experiment and enzyme-linked immunosorbent assay showed that EA treatment significantly relieved spontaneous pain-like behaviors and increased the level of ß-END in inflamed tissue. Injection of anti-END antibody in inflamed tissue blocked this analgesic effect. Flow cytometry and immunofluorescence staining revealed that the EA-induced increase in ß-END was derived from opioid-containing ICAM-1 + /CD11b + immune cells in inflamed tissue. In addition, EA treatment increased the NE content and expression of ß2 adrenergic receptor (ADR-ß2) in inflammatory tissues and upregulated Cxcl1 and Cxcl6 gene expression levels. These findings provide new evidence for the peripheral analgesic effect of acupuncture treatment by recruiting ß-END-containing ICAM-1 + /CD11b + immune cells and increasing the ß-END content at the site of inflammation.

[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.

Effects of moxibustion on serum levels of β-EP, SP and expression of IL-1β and COX-2 protein in brainstem in rats with migraine / 中国针灸

OBJECTIVE@#To observe the effects of moxibustion at "Baihui" (GV 20) and "Dazhui" (GV 14) at different time points on the serum level of β-endorphin (β-EP), substance P (SP) and expression of interleukin-1β (IL-1β) 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 β-EP and SP; the immunohistochemistry method was used to detect the number of positive cells of IL-1β 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 β-EP was decreased (P<0.01), while the serum level of SP, the number of positive cells of IL-1β 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 β-EP was increased (P<0.01), while the serum level of SP, the number of positive cells of IL-1β 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 β-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-1β and COX-2 protein expression in brainstem, and increase the serum level of β-EP, and the optimal effect is observed in the PT group.

[Effect of herbal cake-separated moxibustion on behavioral stress reactions and blood lactic acid level and muscular AMPK/PGC-1α signaling in rats with chronic fatigue syndrome].

OBJECTIVE: To observe the effect of herbal cake-separated moxibustion (HCSM) on serum lactic acid (BLA) level and AMPK/PGC-1α signaling pathway in the quadriceps femoris in chronic fatigue syndrome (CFS) rats, so as to explore its mechanisms underlying improvement of CFS. METHODS: According to the random number table, 50 SD rats were divided into blank control, model, HCSM, sham HCSM and medication (herbal medicine gavage) groups, with 10 rats in each group. The CFS model was established by using chronic restraint and exhaustive swimming, alternately, once daily for 21 days. The herbal cake was made of Xiaoyao Powder (Mental Ease Powder, composed of [Danggui (Radix Angelicae Sinensis), Baishao (Radix Paeoniae Alba), Chaihu (Radix Bupleuri), Fuling (Poria), Baizhu (Rhizoma Atractylodis, Macrocephalae), etc.]. The HCSM was applied to "Shenque" (CV8), "Guanyuan "(CV4), bilateral "Zusanli" (ST36) and "Qimen" (LR14), 5 moxa-cones for each acupoint, once daily for 10 days. For sham HCSM, the excipient was instead of herbal cake, and the same 5 moxa-cones was given as the HCSM group. Rats of the medication group received gavage of Xiaoyao Powder suspension (60 mg·kg-1), once daily for 10 days. The open field test and tail suspension test were conducted for determining the animals' locomotor activity. The blood sample was taken from the abdominal aorta under anesthesia for assaying the levels of serum BLA, chemokine ligand CXCL9 and ß-endorphin (EP) by ELISA. Bilateral quadriceps femoris were sampled for observing histopathological changes after staining with conventional H.E. technique, and for detecting the expression levels of phosphorylated AMP-activated protein kinase (p-AMPK) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) by using immunohistochemistry. RESULTS: Compared with the blank control group, the number of rearing and horizontal grid-crossing times, struggling times of tail suspension test were significantly decreased (P<0.05), and the immobility time was obviously prolonged (P<0.05) in the model group. Compared with the model group, both HCSM and medication groups had a significant increase of rearing, horizontal grid-crossing times and struggling times (P<0.05), and the immobility time had a significant decrease (P<0.05). But there were no significant differences in the total movement distance among the 5 groups (P>0.05), and in the 5 indexes of behavioral measurements between the HCSM and medication groups (P>0.05). The sham HCSM could also evidently increase the struggling times and reduce the immobility time (P<0.05). The contents of serum BLA, CXCL9 and ß-EP were obviously higher in the model group than in the blank control group (P<0.05), as well as remarkably lower in the HCSM and medication groups than in the model group (P<0.05). Whereas the expression levels of muscular p-AMPK and PGC-1α were considerably lower in the model group than in the blank control group (P<0.05), and significantly increased in both HCSM and medication groups relevant to the model group (P<0.05). Compared with the sham HCSM group, the contents of BLA, CXCL9 and ß-EP in serum of the HCSM group and contents of CXCL9, ß-EP in medication group were significantly decreased (P<0.05), and the protein expressions of p-AMPK and PGC-1α in quadriceps femoris in both HCSM and medication groups were significantly increased (P<0.05). H.E. staining showed smaller intercellular space, uneven cytoplasmic staining in some muscle fibers, nucleus pyknosis and condensation, and inflammatory cell infiltration in the model group, which was milder in both HCSM and medication groups. CONCLUSION: HCSM can mitigate the stress behavioral state in CFS rats, which may be related with its functions in lowering the levels of serum BLA, CXCL9 and ß-EP, and activating AMPK/PGC-1α signaling pathway (balancing energy metabolism) in the quadriceps femoris.

Ma's bamboo-based medicinal moxibustion therapy of low back pain in lumbar disc herniation: study protocol for a randomized controlled trial.

BACKGROUND: Lumbar disc herniation (LDH) is a common and frequently occurring disease in clinics. Low back pain and sciatica are the presenting symptoms of LDH. To some extent, it can be considered that measures with the capability to improve low back pain or sciatica have the potential to treat LDH. Ma's bamboo-based medicinal moxibustion therapy can effectively reduce the degree of low back pain and has been widely used. Studies of small sample size have seen significant improvement on pain relief. The aim of this trial is to evaluate the clinical efficacy and safety of Ma's bamboo-based medicinal moxibustion therapy in the treatment of LDH low back pain. METHODS/DESIGN: The trial is a multicenter, randomized, parallel-group, non-inferiority study. Three hundred and twelve patients will be randomly assigned to a Ma's bamboo-based medicinal moxibustion group (n=156) and an acupuncture group (n=156). Patients in each group will receive treatment every day, 6 times a week, 12 times in total. Follow-up will be conducted 14 days after treatment. The primary outcome will be the visual analog scale(VAS) at baseline, after 6 times of treatment, end of treatment, and follow-up. The secondary outcomes will include Oswestry disability indexes (ODI), modified Japanese Orthopaedic Association low back pain (M-JOA) score, serum ß-endorphin (ß-EP), and serum substance P (SP). ß-EP and SP, as well as safety evaluation indexes (routine blood, liver, and kidney function and electrocardiogram), will be measure at baseline and after the end of treatment. The number, nature, and severity of adverse events will be recorded. DISCUSSION: The results of the trial will compare the efficacy of low back pain in LDH between Ma's bamboo-based medicinal moxibustion group and the acupuncture group and will be expected to make a systematic and objective evaluation of the clinical efficacy and safety of Ma's bamboo-based medicinal moxibustion therapy. TRIAL REGISTRATION: ChiCTR2000038725 . Registered on 29 September 2020.

[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.

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.

Human Sensory Neuron-like Cells and Glycated Collagen Matrix as a Model for the Screening of Analgesic Compounds.

Increased collagen-derived advanced glycation end-products (AGEs) are consistently related to painful diseases, including osteoarthritis, diabetic neuropathy, and neurodegenerative disorders. We have recently developed a model combining a two-dimensional glycated extracellular matrix (ECM-GC) and primary dorsal root ganglion (DRG) that mimicked a pro-nociceptive microenvironment. However, culturing primary cells is still a challenge for large-scale screening studies. Here, we characterized a new model using ECM-GC as a stimulus for human sensory-like neurons differentiated from SH-SY5Y cell lines to screen for analgesic compounds. First, we confirmed that the differentiation process induces the expression of neuron markers (MAP2, RBFOX3 (NeuN), and TUBB3 (ß-III tubulin), as well as sensory neuron markers critical for pain sensation (TRPV1, SCN9A (Nav1.7), SCN10A (Nav1.8), and SCN11A (Nav1.9). Next, we showed that ECM-GC increased c-Fos expression in human sensory-like neurons, which is suggestive of neuronal activation. In addition, ECM-GC upregulated the expression of critical genes involved in pain, including SCN9A and TACR1. Of interest, ECM-GC induced substance P release, a neuropeptide widely involved in neuroinflammation and pain. Finally, morphine, the prototype opiate, decreased ECM-GC-induced substance P release. Together, our results suggest that we established a functional model that can be useful as a platform for screening candidates for the management of painful conditions.

Inhibition of POMC neurons in mice undergoing activity-based anorexia selectively blunts food anticipatory activity without affecting body weight or food intake.

Anorexia nervosa (AN) is a debilitating eating disorder characterized by severely restricted eating and significant body weight loss. In addition, many individuals also report engaging in excessive exercise. Previous research using the activity-based anorexia (ABA) model has implicated the hypothalamic proopiomelanocortin (POMC) system. Using the ABA model, Pomc mRNA has been shown to be transiently elevated in both male and female rodents undergoing ABA. In addition, the POMC peptide ß-endorphin appears to contribute to food anticipatory activity (FAA), a characteristic of ABA, as both deletion and antagonism of the µ opioid receptor (MOR) that ß-endorphin targets, results in decreased FAA. The role of ß-endorphin in reduced food intake in ABA is unknown and POMC neurons release multiple transmitters in addition to ß-endorphin. In the current study, we set out to determine whether targeted inhibition of POMC neurons themselves rather than their peptide products would lessen the severity of ABA. Inhibition of POMC neurons during ABA via chemogenetic Designer Receptors Exclusively Activated by Designer Drugs (DREADD) technology resulted in reduced FAA in both male and female mice with no significant changes in body weight or food intake. The selective reduction in FAA persisted even in the face of concurrent chemogenetic inhibition of additional cell types in the hypothalamic arcuate nucleus. The results suggest that POMC neurons could be contributing preferentially to excessive exercise habits in patients with AN. Furthermore, the results also suggest that metabolic control during ABA appears to take place via a POMC neuron-independent mechanism.

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.

Efficacy of Acupuncture on Pain Mechanisms, Inflammatory Responses, and Wound Healing in the Acute Phase of Major Burns: An Experimental Study on Rats.

We investigated acupuncture, a potential contributor for burn care, on physiological and pathological pain mechanisms and systemic and local inflammatory responses in a rat experimental burn model. Forty male Sprague-Dawley rats were divided into two groups. One-hour groups (five rats/group) were observed for 1 hour and included Sh1 (sham/observation), ShA1 (sham + acupuncture/observation), Brn1 (burn/observation), and BrnA1 (burn + acupuncture/observation). Seven-day groups (five rats/group) were observed for 7 days and included Sh7 (sham/observation), ShA7 (sham + acupuncture/observation), Brn7 (burn/observation), and BrnA7 (burn + acupuncture/observation). "Pain-distress scores" were noted daily, and acupuncture was repeated within every wound-dressing change on alternate days. After observation periods, blood samples for interleukin 6 and beta-endorphin and skin biopsies for inflammatory changes and immunohistochemical staining of interleukin 6 were collected for analysis(P < .05). In 1-hour groups, interleukin 6 accumulation in burn wounds of BrnA1 was less than Brn1, with Brn1 having the highest mean blood level (P < .05). Mean beta-endorphin levels were higher in ShA1, Brn1, and BrnA1 than in Sh1 (P < .05). In all 7-day groups, the agonizing period was 48 to 72 hours after burn, with Brn7 most affected (P < .05). Microvessels were multiplied in the Brn7 group, with significantly higher numbers in burn wounds of BrnA7 (P ˂ .05). Burn wounds of BrnA7 had less accumulation of interleukin 6 than Brn7 with the Brn7 group having the highest mean blood level and Sh7, ShA7, and BrnA7 having similarly low levels (P ˃ .05). Beta-endorphin levels in ShA7, Brn7, and BrnA7 were lower than in Sh7 (P < .05). Acupuncture contributed to the management of physiological and pathological pain, modulation of inflammatory responses, and associated enhancement of angiogenesis in the acute phase of burn injury in rats.

Application of Chaihu-Guizhi-Longgu-Muli decoction combined with Liuwei Dihuang Pills in the treatment of menopausal insomnia and its effect on sleep quality.

To explore the application of Chaihu-Guizhi-Longgu-Muli decoction (CGLM) combined with Liuwei Dihuang Pills in the treatment of menopausal insomnia and its effect on sleep quality. The data of 120 menopausal insomnia patients admitted to our hospital from February 2019 to February 2020 were retrospectively analyzed and they were equally divided into the experimental group (n=60) and the control group (n=60) according to the order of admission. All patients were treated with Liuwei Dihuang Pills, and the experimental group was additionally given CGLM. The Pittsburgh Sleep Quality Index (PSQI), estrogen level, negative emotion score, quality of life score, serum ß-endorphin (ß-EP) level, serotonin level (5-HT) and treatment effective rate were compared between the two groups of patients. After treatment, the experimental group obtained markedly lower PSQI scores and negative emotion scores than the control group (P<0.001). The estrogen levels, ß-EP levels and 5-HT levels of the experimental group after treatment were significantly better than those of the control group (P<0.001). Higher quality of life scores and treatment effective rates were observed in the experimental group after treatment than the control group (P<0.001). CGLM combined with Liuwei Dihuang Pills can regulate the serum hormone levels of patients with menopausal insomnia, reduce negative emotions and improve sleep quality and quality of life, which merits clinical promotion.

The Efficacy of Moxibustion on the Serum Levels of CXCL1 and ß-EP in Patients with Rheumatoid Arthritis.

OBJECTIVE: This study aims to evaluate the efficacy of moxibustion on joint swelling and pain and the levels of C-X-C motif chemokine ligand 1 (CXCL1), ß-endorphin (ß-EP) in serum of rheumatoid arthritis (RA) patients and to investigate the anti-inflammatory and analgesic mechanism of moxibustion on improving RA. METHODS: Sixty-eight patients with RA were randomly and equally classified into the control and treatment groups. The control group was treated with routine drug therapy, while the treatment group received routine drug therapy and moxibustion. Both groups were treated for eight weeks. The symptoms and laboratory indicators of RA patients were compared in the two groups before and after intervention. RESULTS: Sixty-one patients completed the study: four patients dropped out from the treatment group and three from the control group. Trial endpoints were change (∆) in symptoms, measured by Ritchie's articular index (RAI), swollen joint count (SJC), and laboratory indicators, measured by the level of CXCL1, ß-EP, tumor necrosis factor-a (TNF-α), and interleukin-1ß (IL-1ß). ∆RAI, ∆SJC, ∆CXCL1, ∆ß-EP, ∆TNF-α, and ∆IL-1ß in the treatment group were superior to the control group (13.50 [14.50] versus 6.00 [13.00] in ∆RAI, 4.00 [3.00] versus 2.00 [4.00] in ∆SJC, 0.04 ± 0.79 ng/mL versus -0.01 ± 0.86 ng/mL in ∆CXCL1, -2.43 [5.52] pg/mg versus -0.04 [4.09] pg/mg in ∆ß-EP, 3.45 [5.90] pg/mL versus 1.55 [8.29] pg/mL in ∆TNF-α, and 6.15 ± 8.65 pg/mL versus 1.28 ± 8.51 pg/mL in ∆IL-1ß; all P < 0.05). CONCLUSION: Moxibustion can improve the joint swelling and pain symptoms in patients with RA, which may be related to the fact that moxibustion can reduce the release of inflammatory factors in patients with RA and downregulate the level of CXCL1 and increase the level of ß-EP at the same time. This trial is registered with ChiCTR-IOR-17012282.

Effect of Chaihu-jia-Longgu-Muli decoction on withdrawal symptoms in rats with methamphetamine-induced conditioned place preference.

Traditional Chinese medicine detoxification prescription Chaihu-jia-Longgu-Muli decoction (CLMD) relieves depressive symptoms in patients withdrawing from methamphetamine. In the present study, we assessed the effects of CLMD on methamphetamine withdrawal in rats. A methamphetamine-intoxicated rat model was established. Rats were randomly divided into the control, model, high-dosage, medium-dosage, and low-dosage groups, receiving high, medium, and low doses of CLMD, respectively. Weekly body weight measurements revealed that rats treated with methamphetamine had the lowest body weight. The conditioned place preference (CPP) experiment revealed that methamphetamine-intoxicated rats stayed significantly longer in the drug-paired chamber than the control rats. However, after administering high-dosage CLMD, the amount of time the rats spent in the drug-paired chamber was significantly less than that of the model rats. Our open-field test revealed that the model group had lower crossing and rearing scores than the control group. Additionally, rats that received CLMD treatment exhibited higher crossing and rearing scores than the model rats. Striatal dopamine (DA), 5-hydroxytryptamine (5-HT), and endorphins (ß-EP) and serum interleukin (IL)-1α and IL-2 concentrations were estimated. Rats in the model group had lower striatal DA, 5-HT, and ß-EP and higher serum IL-1α and IL-2 concentrations than those in the control group. High-dosage CLMD administration significantly changed the concentrations of these molecules, such that they approached normal concentrations. In general, CLMD could prevent the development of methamphetamine-induced withdrawal symptoms in rats by increasing the DA, 5-HT, and ß-EP and lowering the IL-1α and IL-2 concentrations.

Central µ-Opioid Receptor Antagonism Blocks Glucoprivic LH Pulse Suppression and Gluconeogenesis/Feeding in Female Rats.

Energetic status often affects reproductive function, glucose homeostasis, and feeding in mammals. Malnutrition suppresses pulsatile release of the gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) and increases gluconeogenesis and feeding. The present study aims to examine whether ß-endorphin-µ-opioid receptor (MOR) signaling mediates the suppression of pulsatile GnRH/LH release and an increase in gluconeogenesis/feeding induced by malnutrition. Ovariectomized female rats treated with a negative feedback level of estradiol-17ß (OVX + low E2) receiving 2-deoxy-D-glucose (2DG), an inhibitor of glucose utilization, intravenously (iv) were used as a malnutrition model. An administration of D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), a selective MOR antagonist, into the third ventricle blocked the suppression of the LH pulse and increase in gluconeogenesis/feeding induced by iv 2DG administration. Histological analysis revealed that arcuate Kiss1 (kisspeptin gene)-expressing cells and preoptic Gnrh1 (GnRH gene)-expressing cells co-expressed little Oprm1 (MOR gene), while around 10% of arcuate Slc17a6 (glutamatergic marker gene)-expressing cells co-expressed Oprm1. Further, the CTOP treatment decreased the number of fos-positive cells in the paraventricular nucleus (PVN) in OVX + low E2 rats treated with iv 2DG but failed to affect the number of arcuate fos-expressing Slc17a6-positive cells. Taken together, these results suggest that the central ß-endorphin-MOR signaling mediates the suppression of pulsatile LH release and that the ß-endorphin may indirectly suppress the arcuate kisspeptin neurons, a master regulator for GnRH/LH pulses during malnutrition. Furthermore, the current study suggests that central ß-endorphin-MOR signaling is also involved in gluconeogenesis and an increase in food intake by directly or indirectly acting on the PVN neurons during malnutrition in female rats.

Green Light Antinociceptive and Reversal of Thermal and Mechanical Hypersensitivity Effects Rely on Endogenous Opioid System Stimulation.

Benefits of phototherapy were characterized in multiple diseases including depression, circadian rhythm disruptions, and neurodegeneration. Studies on migraine and fibromyalgia patients revealed that green light-emitting diodes (GLED) exposure provides a pragmatic and safe therapy to manage chronic pain. In rodents, GLED reversed hypersensitivity related to neuropathic pain. However, little is known about the underlying mechanisms of GLED efficacy. Here, we sought to understand how green light modulates the endogenous opioid system. We first characterized how exposure to GLED stimulates release of ß-endorphin and proenkephalin in the central nervous system of male rats. Moreover, by individually editing each of the receptors, we found that µ- and δ-opioid receptors are required for green light's antinociceptive effect in naïve rats and a model of HIV-induced peripheral neuropathy. We investigated how GLED could increase pain thresholds, and explored its potential in reversing hypersensitivity in a model of HIV-related neuropathy. Through behavioral and gene editing approaches, we identified that green light provides antinociception via modulation of the endogenous opioid system in the spinal cord. This work identifies a previously unknown mechanism by which GLED can improve pain management. Clinical translation of these results will advance the development of an innovative therapy devoid of adverse effects. PERSPECTIVE: Development of new pain management therapies, especially for HIV patients, is crucial as long-term opioid prescription is not recommended due to adverse side effects. Green light addresses this necessity. Characterizing the underlying mechanisms of this potentially groundbreaking and safe antinociceptive therapy will advance its clinical translation.

Effects of laughter yoga on hemodialysis patients' plasma-beta endorphin levels, pain levels and sleep quality: A randomized controlled trial.

This study evaluates the effects of "laughter yoga" on the plasma beta-endorphin levels, pain levels and sleep quality of hemodialysis patients. It is a randomized controlled trial. The study was carried out between July and October 2018. A total of 68 patients receiving hemodialysis treatment at two different dialysis centers were included in the study. The duration of the laughter yoga was 30 min, and a total of 16 sessions were performed on a twice-weekly basis. The data were collected by using a socio-demographic information form, the Visual Analog Scale and the Pittsburgh Sleep Quality Index, and blood samples were collected to determine beta-endorphin levels. Following the laughter yoga implementation, the pain level of the intervention group patients significantly decreased, and their sleep quality significantly improved. No significant change occurred in the patients' beta-endorphin levels. Laughter yoga was effective in reducing pain and increasing sleep quality.

ß-endorphin differentially contributes to food anticipatory activity in male and female mice undergoing activity-based anorexia.

Anorexia nervosa (AN) has a lifetime prevalence of up to 4% and a high mortality rate (~5-10%), yet little is known regarding the etiology of this disease. In an attempt to fill the gaps in knowledge, activity-based anorexia (ABA) in rodents has been a widely used model as it mimics several key features of AN including severely restricted food intake and excessive exercise. Using this model, a role for the hypothalamic proopiomelanocortin (POMC) system has been implicated in the development of ABA as Pomc mRNA is elevated in female rats undergoing the ABA paradigm. Since the Pomc gene product α-MSH potently inhibits food intake, it could be that elevated α-MSH might promote ABA. However, the α-MSH receptor antagonist SHU9119 does not protect against the development of ABA. Interestingly, it has also been shown that female mice lacking the mu opioid receptor (MOR), the primary receptor activated by the Pomc-gene-derived opioid ß-endorphin, display blunted food anticipatory behavior (FAA), a key feature of ABA. Thus, we hypothesized that the elevation in Pomc mRNA observed during ABA may lead to increased ß-endorphin concentrations and MOR activation to promote ABA. Further, given the known sex differences in AN and ABA, we hypothesized that MORs may contribute differentially in male and female mice. Using wild-type and MOR knockout mice of both sexes, a MOR antagonist and careful analysis of food anticipatory behavior and ß-endorphin levels, we found 1) increased Pomc mRNA levels in both female and male mice that underwent ABA, 2) increased ß-endorphin in female mice that underwent ABA, and 3) blunted FAA in both sexes in response to MOR genetic deletion yet blunted FAA only in males in response to MOR antagonism. The results presented provide support for both hypotheses and suggest that it may be the ß-endorphin resulting from increased Pomc transcription that supports the development of some features of ABA.