Song-Ping Han

Electroacupuncture: mechanisms and clinical application.

Acupuncture is an ancient Chinese method to treat diseases and relieve pain. We have conducted a series of studies to examine the mechanisms of this ancient method for pain relief. This article reviews some of our major findings. Our studies showed that acupuncture produces analgesic effect and that electroacupuncture (EA) is more effective than manual acupuncture. Furthermore, electrical stimulation via skin patch electrodes is as effective as EA. The induction and recovering profiles of acupuncture analgesia suggest the involvement of humoral factors. This notion was supported by cross-perfusion experiments in which acupuncture-induced analgesic effect was transferred from the donor rabbit to the recipient rabbit when the cerebrospinal fluid (CSF) was transferred. The prevention of EA-induced analgesia by naloxone and by antiserum against endorphins suggests that endorphins are involved. More recent work demonstrated the release of endorphins into CSF following EA. In addition, low frequency (2 Hz) and high frequency (100 Hz) of EA selectively induces the release of enkephalins and dynorphins in both experimental animals and humans. Clinical studies suggesting its effectiveness for the treatment of various types of pain, depression, anxiety, spinally induced muscle spasm, stroke, gastrointestinal disorders, and drug addiction were also discussed.

Prenatal hyperandrogenic environment induced autistic-like behavior in rat offspring

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by persistent impairment in social communication and social interaction. Recent studies revealed that environmental factors, especially the intrauterine developmental environment, played important roles in the development of ASD. It is hypothesized that maternal hyperandrogenism during pregnancy may increase the susceptibility of the fetus to ASD. In the present study, pregnant rats were treated with a low dose of letrozole (1μg/kg/day) in an attempt to produce a hyperandrogenic intrauterine environment for the developing fetus. Results showed that rat pups prenatally exposed to hyperandrogenic intrauterine environment emitted less number of ultrasonic vocalizations when isolated from their dams and littermates. Additionally, the female rats in the treatment group spent less time in social interaction in adolescence and exhibited impaired heterosexual interaction in adult. Moreover, the duration of social interaction and heterosexual interaction of the female offspring were negatively correlated with maternal serum testosterone levels during pregnancy. These results suggest that prenatal exposure to hyperandrogenic intrauterine environment could induce autistic-like behavior in female rats and maternal hyperandrogenism during pregnancy should be considered as a potential risk factor for the etiology of ASD.

Mothers of Autistic Children: Lower Plasma Levels of Oxytocin and Arg-Vasopressin and a Higher Level of Testosterone

Background Autism is a pervasive neurodevelopmental disorder,thought to be caused by a combination of genetic heritability and environmental risk factors. Some autistic-like traits have been reported in mothers of autistic children. We hypothesized that dysregulation of oxytocin (OXT), Arg-vasopressin (AVP) and sex hormones, found in autistic children, may also exist in their mothers. Methods We determined plasma levels of OXT (40 in autism vs. 26 in control group), AVP (40 vs. 17) and sex hormones (61 vs. 47) in mothers of autistic and normal children by enzyme immunoassay and radioimmunoassay, respectively and investigated their relationships with the children’s autistic behavior scores (Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC)). Results Significantly lower plasma concentrations of OXT (p<0.001) and AVP (p<0.001), as well as a higher level of plasma testosterone (p<0.05), were found in mothers of autistic children vs. those of control. The children’s autistic behavior scores were negatively associated with maternal plasma levels of OXT and AVP. Conclusions These results suggest that dysregulation of OXT, AVP and/or testosterone systems exist in mothers of autistic children, which may impact children’s susceptibility to autism.

Transcutaneous electrical acupoint stimulation in children with autism and its impact on plasma levels of arginine-vasopressin and oxytocin: a prospective single-blinded controlled study.

Acupuncture increases brain levels of arginine-vasopressin (AVP) and oxytocin (OXT), which are known to be involved in the modulation of mammalian social behavior. Transcutaneous electrical acupoint stimulation (TEAS) is often used clinically to produce a similar stimulation to that of acupuncture on the acupoints. In the present study, TEAS was applied to children with autism to assess its therapeutic efficacy. Seventy-six autistic children receiving rehabilitation training were divided into 2 groups: a treatment group receiving TEAS 30min per day, 5 days per week for 12 weeks (n=37) and a control group without TEAS treatment (n=39). A series of rating scales was used in outcome assessment. Plasma levels of AVP and OXT were determined by enzyme immunoassay (EIA) before and after treatment. The TEAS group showed a significant improvement over the control in their emotional response, fear or anxiety, level/consistency of intellective relations and general impressions on the Childhood Autism Rating Scale (CARS) as well as improvements in the sensory and related factors in the Autism Behavior Checklist (ABC). In addition, the varieties of accepted food increased after TEAS treatment. It appears that TEAS was effective in autistic children who showed passive and aloof behavior, but not in those who were active but odd. The plasma level of AVP was significantly higher in the TEAS group than in the control group after the intervention. In addition, the change in the plasma AVP level paralleled the improvement of some of the behavior factors in CARS, including adaptation to environmental change, listening response, perceptive response and fear or anxiety. It is concluded that TEAS is effective for the treatment of autistic children with a passive and aloof social interaction style. Changes in plasma levels of AVP and possibly OXT may be involved in mediating the therapeutic effect of TEAS.

Genes Related to Oxytocin and Arginine-Vasopressin Pathways: Associations with Autism Spectrum Disorders

Abstract Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorders characterized by impaired social interactions, communication deficits, and repetitive behavior. Although the mechanisms underlying its etiology and manifestations are poorly understood, several lines of evidence from rodent and human studies suggest involvement of the evolutionarily highly-conserved oxytocin (OXT) and arginine-vasopressin (AVP), as these neuropeptides modulate various aspects of mammalian social behavior. As far as we know, there is no comprehensive review of the roles of the OXT and AVP systems in the development of ASD from the genetic aspect. In this review, we summarize the current knowledge regarding associations between ASD and single-nucleotide variants of the human OXT-AVP pathway genes OXT, AVP, AVP receptor 1a (AVPR1a), OXT receptor (OXTR), the oxytocinase/vasopressinase (LNPEP), and ADP-ribosyl cyclase (CD38).

EFFECT OF CALCIUM ION ON ANALGESIA OF OPIOID PEPTIDES

The analgesic effect produced by subcutaneous injection (SC) of morphine was antagonized by intracerebroventricular (ICV) but not intrathecal (ITH) injection of CaCl2. While ITH CaCl2 was devoid of any effect on the analgesia induced by ITH morphine, it did antagonize the analgesic effect produced by ITH injection of dynorphin A or (D-Pen2,D-Pen5)-enkephalin (DPDPE). In accordance with this, the uptake of 45Ca by synaptosomes prepared from the dorsal column of rat spinal cord was suppressed by dynorphin A or DPDPE, but not by morphine. The results imply that different kinds of opioid ligands might have different mechanisms of action at discrete areas of the CNS. Blockade of neuronal Ca2+ uptake may serve as an important mechanism for morphine analgesia in the brain as well as DPDPE and dynorphin A analgesia in the spinal cord.

Electro-acupuncture improves the social interaction behavior of rats

Oxytocin (OXT) and arginine-vasopressin (AVP) are two closely related neuropeptides and implicated in the regulation of mammalian social behaviors. A prior clinical study in our laboratory suggested that electro-acupuncture (EA) alleviated social impairment in autistic children accompanied by changes of peripheral levels of OXT and AVP. However, it remains unclear whether EA stimulation had an impact on central OXT and AVP levels. In the present study, rats were subjected to a single session of EA (sEA) or repeated sessions of EA (rEA). Following the stimulation, mRNA levels and peptide levels of OXT/AVP systems were determined. The results showed that sEA led to region-specific up-regulation of OXT and AVP mRNA levels in the hypothalamus where the peptides were produced, without affecting the content of OXT and AVP in the hypothalamus and peripheral blood. The rEA of 5 sessions in 9 days was given to the low socially interacting (LSI) rats. LSI rats that underwent rEA showed significant improvement of social behavior characterized by spending more time investigating the strange rats in the three-chamber sociability test. The improved sociability was accompanied by an up-regulation of mRNA and the peptide levels of OXT or AVP in SON of the hypothalamus as well as a significant increase of the serum level of AVP. It is concluded that activation of OXT/AVP systems may be associated with the pro-social effect caused by EA stimulation.

Effects of chronic restraint stress on social behaviors and the number of hypothalamic oxytocin neurons in male rats.

Oxytocin (OXT) and vasopressin (AVP) are considered to be related to mammalian social behavior and the regulation of stress responses. The present study investigated the effects of chronic homotypic restraint stress (CHRS) on social behaviors and anxiety, as well as its repercussions on OXT- and AVP-positive neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) nuclei in rat. Male Sprague-Dawley rats receiving CHRS were exposed to repeated restraint stress of 30min per day for 10days. Changes in social approach behaviors were evaluated with the three-chambered social approach task. Changes in anxiety-like behaviors were evaluated in the light-dark box test. The number of neurons expressing oxytocin and/or vasopressin in PVN and SON were examined by immunohistochemistry techniques. The results demonstrated that social approach was increased and anxiety was decreased following 10-day exposure to CHRS. Furthermore, the number of OXT-immunoreactive cells in PVN was increased significantly, whereas no change in SON was seen. The number of AVP immunoreactive cells either in PVN or SON was unaffected. The results of this study suggest that certain types of stress could be effective in the treatment of social dysfunction in persons with mental disorders such as autism, social anxiety disorder. The therapeutic effects may be mediated by changes in the function of OXT neurons in PVN.

The Role of the Oxytocin/Arginine Vasopressin System in Animal Models of Autism Spectrum Disorder

The nonapeptides oxytocin (OXT) and arginine vasopressin (AVP) are two key mediators in regulating various aspects of mammalian social behaviours. There are several lines of evidence that genetic variants of the OXT/AVP system exist in autism spectrum disorder (ASD) and that this system is dysfunctional at least in some ASD entities. These findings have stimulated the interest to perform studies testing the potential therapeutic application of OXT/AVP in ASD. In this respect animal models are critical for investigating the pathophysiology and for compound screening leading to new therapeutic approaches. Based on findings in animal models that show alterations of the OXT/AVP system, it has been hypothesised that single- or multiple-dose administration or the stimulation of endogenous release can improve several social deficits. Here we comprehensively review the role of the OXT/AVP system in social recognition, social interaction and maternal behaviour in the light of different ASD animal models and patient studies. We further discuss implications for OXT/AVP-related pharmacological interventions to alleviate social deficits in ASD in the future.

Use of electroacupuncture and transcutaneous electrical acupoint stimulation in reproductive medicine: a group consensus

With the rapid development of assisted reproductive technology, various reproductive disorders have been effectively addressed. Acupuncture-like therapies, including electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS), become more popular world-wide. Increasing evidence has demonstrated that EA and TEAS are effective in treating gynecological disorders, especially infertility. This present paper describes how to select acupoints for the treatment of infertility from the view of theories of traditional Chinese medicine and how to determine critical parameters of electric pulses of EA/TEAS based on results from animal and clinical studies. It summarizes the principles of clinical application of EA/TEAS in treating various kinds of reproductive disorders, such as polycystic ovary syndrome (PCOS), pain induced by oocyte retrieval, diminished ovarian reserve, embryo transfer, and oligospermia/asthenospermia. The possible underlying mechanisms mediating the therapeutic effects of EA/TEAS in reproductive medicine are also examined.概要本文从传统针刺治疗不孕症的选穴依据与现代电针/经皮穴位电刺激技术的相关原理着手,从最优刺激参数选择、穴位辨证、疗程与治疗次数的确定及基本原理等方面阐述了电针/经皮穴位电刺激技术在多囊卵巢综合症、取卵镇痛、卵巢储备功能降低、胚胎移植以及男性少/弱精症等生殖领域中的具体应用。首次对电针/经皮穴位电刺激技术在生殖领域优势病种中的应用进行了系统的分析和总结,在最优刺激参数选择、穴位辨证、疗程与治疗次数的确定等方面提出了一系列专家共识,并为临床实践提供了指导意见和理论依据。