An effectiveness study comparing acupuncture, physiotherapy, and their combination in poststroke rehabilitation: a multicentered, randomized, controlled clinical trial.

CONTEXT: Stroke is a leading cause of death and disability worldwide, being the third leading cause of death in the United States and the second and third most common causes of death in Chinese cities and rural areas, respectively. Evaluation of different rehabilitative modalities appears necessary to optimize treatment. OBJECTIVES: To compare acupuncture and physiotherapy for effectiveness and reliability in treating hemiplegic patients after stroke. DESIGN: The research team designed a multicentered, three-arm, randomized controlled trial. Power calculations revealed a targeted sample size of 310 participants. SETTING: The study took place at seven in-patient hospitals in China. PARTICIPANTS: The research team screened a total of 310 patients. Of that number, 274 completed the study, 15 did not meet the inclusion/exclusion criteria, and 21 dropped out. Adverse events were rare (less than 1%), mild, and temporary. INTERVENTION: The research team randomly divided participants into three groups that all received conventional care as needed-including psychological counseling, standard nursing care, and daily medical evaluation plus (1) acupuncture, (2) physiotherapy, or (3) acupuncture plus physiotherapy. The participants received treatments once a day, 6 days a week for 4 weeks. OUTCOME MEASURES: The research team evaluated all patients at baseline, after 2 weeks, and after 4 weeks using the Fugl-Meyer Assessment of Physical Performance (FMA), a modified Barthel Index (BI), and the Neurologic Defect Scale (NDS). RESULTS: No significant differences existed between the three groups at baseline. Compared to baseline, participants in all groups improved their FMA, BI, and NDS scores by the end of week 2 (P≤.05) and further improved by the end of week 4 (P≤.05) The study found no statistically significant differences in outcomes between the three groups after treatment (P>.05). CONCLUSION: Acupuncture plus conventional care was similar in effectiveness to physiotherapy treatment plus conventional care for poststroke rehabilitation. The study found no synergistic effects for the combination of acupuncture and physiotherapy in addition to conventional care; that combination of treatments was no more effective than either treatment by itself. The effectiveness and lack of adverse events associated with acupuncture in this study suggest that it may represent an additional treatment option for stroke patients.

Active components of common traditional Chinese medicine decoctions have antioxidant functions.

Many traditional Chinese medicine (TCM) decoctions are proven to have multiple functions in animal production. These decoctions are seldom recognized by the international scientific community because the mechanisms of action are not clearly elucidated. According to TCM theory, Cortex Phellodendri (COP), Rhizoma Atractylodes (RA), Agastache Rugosa (AR), and Gypsum Fibrosum (GF) can be used to formulate a medicinal compound that prevents or cures animal disease caused by heat stress. The aim of this research was to study the regulatory functions of the active components of TCM and to elucidate the effects of different TCM decoctions on antioxidant activity and lipid peroxide content, using in vitro and in vivo models of heat stress. For in vitro experiments, intestinal crypt-like epithelial cell line-6 (IEC-6) cells were employed to evaluate the effects of the active components of COP, RA, AR, and GF. For in vivo experiments, forty-eight 2-mo-old Chinese experimental mini-pigs (7.20 ± 0.02 kg) were randomly assigned to 4 groups: a normal-temperature group (NTG); a high-temperature group (HTG); HTG treated with COP, RA, AR, and GF (1:1:1:1, TCM1); and HTG treated with COP, RA, AR, and GF (1:1:1:0.5, TCM2). Results showed that the active components of the COP, RA, AR, and GF increased (P < 0.05) the proliferation and viability of heat-stressed IEC-6 cells and that the most effective treatment doses of COP alkaloid, RA Aetherolea, Herba Agastachis Aetherolea, and GF water extract were 200, 100, 100, and 200 µg/mL, respectively. All 4 active components increased (P < 0.05) superoxide dismutase, glutathione peroxidase activities, and glutathione content, and decreased (P < 0.05) malondialdehyde content with respect to the heat-stressed group to concentrations similar to those seen in NTG. In vivo experiments demonstrated that TCM1 and TCM2 improved (P < 0.05) the poor growth performance seen in HTG pigs. The superoxide dismutase, glutathione peroxidase activities, and malondialdehyde content in porcine jejunum treated with TCM1 and TCM2 were not different (P > 0.05) from those seen in the NTG and were better (P < 0.05) than results seen in the HTG. Overall, it appeared that TCM2 was more effective than TCM1 in ameliorating the effects of heat stress in pigs. In conclusion, this study revealed that the active components of common TCM decoctions have antioxidant functions.

Melatonin attenuates the intensity of beta-endorphin immunoreactivity in the arcuate nucleus of rat hypothalamus.

The present study was undertaken to observe the effect of exogenously administered melatonin on the intensity of beta-endorphin (beta-Ep) immunoreactivity of the neuron in the arcuate nucleus of rat hypothalamus with an aim to explore the possible mechanisms of the analgesic effect of melatonin. The experimental rats were divided into two groups, one injected intraperitoneally with melatonin (110 mg/kg) and the other with only a vehicle. One hour after injection, the brain was processed for coronal sections, which were stained with immunohistochemical ABC technique. The integral optical density (IOD) and mean optical density (OD) of the stained sections were measured with a computer-assisted image-processing and analytical system. beta-Ep immunoreactivity was much decreased in the sections treated with melatonin and the IOD and OD were also decreased significantly (P<0.01; P<0.05). The above results suggest that melatonin may result in a decrease of beta-Ep content in the arcuate nucleus, as a result of increased beta-Ep release induced by administration of melatonin. It is likely that the analgesic effect of melatonin may be in part mediated by the release of beta-endorphin from the arcuate nucleus.

Effects of fenfluramine combined with electroacupuncture on monoamine release in periaqueductal gray of rat brain.

AIM: To study the changes of monoamines in ventrolatoral periaqueductal gray of rat brain before and after electroacupuncture (EA) analgesia (EAA) was enhanced by fenfluramine (Fen), a 5-hydroxytryptamine (5-HT) releaser. METHODS: Monoamines were collected by in vivo microdialysis and measured by HPLC connected with electrochemical detector. RESULTS: The level of norepinephrine (Nor) after EA was decreased (P < 0.05 vs NS group). The contents of 5-HT, 5-hydroxyindol acetic acid (5-HIAA), dopamine (DA), and homovanillic acid (HVA) in periaqueductal gray dialysate were increased (P < 0.05 vs NS group). When Fen was combined with EA, the level of 5-HT and 5-HIAA were further increased (P < 0.05 vs NS + EA group). There was no obvious change of Nor, DA, and HVA. CONCLUSION: Fen potentiating EAA may be related to further activation of serotoninergic system.

[Effect of intrathecal injection of dopamine receptor agonists/antagonists on pain and acupuncture analgesia in rats].

Some selective dopamine receptor agonists and antagonists were tested on rat tail flick model to investigate the role of D1 and D2 dopamine receptor in pain and acupuncture analgesia (AA). It was found that intrathecal administration (i.t.) of D2 receptor agonist LY171555 or D1/D2 receptor agonist apomorphine increased pain threshold and had a potentiating effect on AA. In contrast, D1 receptor agonist SKF38393 had no effect. It D1 receptor antagonist SCH23390 or D2 receptor antagonist sulpiride attenuated the effect of AA. The results suggest that D2 receptor is involved in pain modulation and activation of D2 receptor and enhances AA in the spinal cord, while such effect is absent in D1 receptor and inactivation of D1 receptor attenuates AA.

[Alteration of monoamine contents in microdialysate following droperidol enhanced electroacupuncture].

The monoamine contents in microdialysate from rat brain before and after droperidol (DRO), a dopamine (DA) antagonist, enhanced electroacupuncture-induced analgesia (EA) were measured using techniques of in vivo microdialysis and high performance liquid chromatography with electrochemical detection (HPLC-EC), so as to investigate the monoamine mechanism of the potentiating effect of DRO on acupuncture analgesia (AA). The results showed that the levels of DA and its metabolites homovanillic acid (HVA) in perfusate increased after EA (P < 0.05 or 0.01), and further increased after DRO + EA (P < 0.05 and 0.01, vs EA treatment). A significant decrease in norepinephrine (NE) content after EA (P < 0.01) was observed, but no further change after DRO + EA (P > 0.05, vs EA treatment). The contents of 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA) we elevated after EA treatment, and a further elevation in 5-HT and 5-HIAA contents induced by DRO + EA was noted. The results in the present study suggest that DRO potentiated AA not only via antagonizing the activity of dopaminergic system, but also by coordinating the activities of other monoamines in the brain.

Preproopiomelanocortin and preprodynorphin mRNA expressions in rat brain after electroacupuncture + droperidol.

AIM: To study the expression of preproopiomelanocortin (POMC) and preprodynorphin (PPD) mRNA following the combination of electroacupuncture (EA) with droperidol (Dro), a dopamine receptor antagonist. METHODS: The brains and spinal cords of Sprague-Dawley rats were sectioned after combination of EA with Dro, and the gene expression was investigated using nonradioactive in situ hybridization histochemistry (ISHH). RESULTS: Ten hours after EA, the POMC mRNA expression was enhanced; the expression was further enhanced when EA was combined with Dro. The expression of PPD mRNA showed regional difference in central nervous system (CNS): in spinal cord, EA enhanced the PPD mRNA expression and the combination of EA with Dro further promoted the expression; in the brain, the PPD mRNA expression after EA or combination of EA with Dro showed no obvious change in most regions (caudate-putamen, accumbens, arcuate nucleus of hypothalamus) or was decreased in supraoptic nucleus. CONCLUSION: Dro combined with EA promoted the expression of POMC mRNA in CNS and PPD mRNA in spinal cord, but reduced or had no effect on PPD mRNA expression in the brain.

[Effect of intrathecal or intracerebroventricular administrition of OFQ on pain threshold and acpuncture analgesia in rats].

Orphanin FQ (OFQ) is a newly discovered 17-amino-acid peptide capable of inducing hyperalgesia. In the present study, the effects of OFQ on basal pain threshold and acupuncture anlgesia (AA) in rats were observed using the tail-flick test. It was found that intrathecal (i.t.) or intracerebroventricular (i.c.v.) administrition of 0.1 microgram OFQ had no effect on basal pain threshold of rats, while 1 microgram OFQ could lower the threshold. However, OFQ at both the doses (0.1 or 1.0 microgram) administered by either i.t. or i.c.v. injection could antagonize AA with that occuring in the brain being more prominent then in the spinal cord. When the rats were repeatedly treated with antisense oligonucleotide to block synthesis of OFQ receptor, pain threshold increased significantly. At such instance, when the OFQ was combined with acupuncture, the effect of AA showed no obvious change. The above results show that the OFQ at small dose has no effect on pain threshold but can lower it at larger dose; while in both cases OFQ can antagonize AA.

Antagonistic action of orphanin FQ on acupuncture analgesia in rat brain.

The influence of orphanin FQ (OFQ) (a newly discovered 17-amino acid peptide) on acupuncture analgesia (AA) was assessed in rat tail-flick model. Intracerebroventricular (i.c.v.) injection of OFQ (1 microgram) elicited a significant decrement of pain threshold which was abolished by the repeated pretreatment with antisense oligonucleotide (ASO) to OFQ receptor. Electroacupuncture (EA) induced an obvious analgesic effect; when OFQ was used combined with EA, it showed a dose-dependent effect on antagonizing the EA analgesia. When rat was repeatedly i.c.v. injected with ASO to block the synthesis of OFQ receptor, the EA analgesia was enhanced markedly. In this instance, the OFQ did not show antagonistic effect on EA analgesia any more. The results suggest that the OFQ play its antagonistic role on EA analgesia via activating OFQ receptor.

Expressions of preproenkephalin mRNA during electroacupuncture analgesia enhanced by fenfluramine.

AIM: To study the changes of preproenkephalin (PPE) mRNA in rat brain in response to electroacupuncture (EA) combined with fenfluramine (Fen), a releaser of 5-HT. METHODS: In situ hybridization histochemistry technique was used to observe the expression of PPE mRNA in rat brain during EA analgesia potentiated by Fen. RESULTS: The greatest relative increase of PPE mRNA was seen in lumbar spinal cord (laminae I & II), nucleus raphe magnus, dorsal raphe nucleus, periaqueductal gray, interpeduncular nucleus, preoptic lateral area, amygdala nucleus and caudate-putamen (P < 0.01, vs NS + EA). Moderate increases were found in lateral septal, preoptic medial area, hypothalamus ventromedial nucleus, lumbar spinal laminae III & IV (P < 0.05, vs NS + EA). Thalamus showed no statistical significant change in PPE mRNA. CONCLUSION: The enhancing of PPE mRNA in relative brain nuclei is involved in potentiating action of Fen on EA.

Binding sites of mu receptor increased when acupuncture analgesia was enhanced by droperidol: an autoradiographic study.

AIM: To study if mu receptor participates in the process of potentiation of droperidol (Dro) on acupuncture analgesia (AA). METHODS: Autoradiographic technic was used. Ohmefentanyl, a highly selective ligand of mu receptors, was used in radio-receptor binding assay in Sprague-Dawley rat brain sections. RESULTS: The binding sites of [beta-3H, p-benzoyl-3H]ohmefentanyl were increased greatly in many nuclei of rat brain after AA, and were further increased when AA was enhanced by Dro. Higher increase was seen in caudate nucleus, accumbens, periaqueductal gray (PAG), interpeduncular nucleus, amygdala (P < 0.01 vs rats treated with electroacupuncture alone); moderate increase was noted in thalamus, lateral area of hypothalamus, spinal dorsal horn (P < 0.01 or 0.05); slight increase appeared in septum, preoptic area, hippocampus, substantia nigra (P < 0.05). CONCLUSION: Mu opioid receptors mediated the Dro-induced enhancement of AA.

Preproenkephalin mRNA enhanced by combination of droperidol with electroacupuncture.

AIM: To study the expression of preproenkephalin (PPE) mRNA following electroacupuncture (EA) combined with droperidol (Dro), an antagonist of dopamine receptors. METHOD: The brains of Sprague-Dawley rats were sectioned after combination of EA with Dro and nonradioactive in situ hybridization histochemistry (ISHH) technic was used. RESULTS: Ten hours after EA, the expression of PPE mRNA was enhanced; when EA was combined with Dro, the expression of PPE mRNA was further enhanced in many pain-modulation-related nuclei, such as caudate-putamen, accumbens, septal nucleus, diagonal band nucleus, amygdala, hypothalamus, periaqueductal gray (PAG), interpeduncular nucleus, substantia nigra, and the dorsal horn of spinal cord (layer I-II and III-IV). CONCLUSION: Dro promoted EA's action on the PPE mRNA expression, which underlie the mechanisms of Dro potentiation on acupuncture analgesia.

[The potentiation effect of haloperidol on the binding of etorphine to brain membranes in acupuncture analgesia].

[3H]-etorphine was used in receptor binding studies on membrane preparation from rabbit brain. Scatchard analysis revealed that rabbit brain had two different affinity binding sites. In the high affinity site, the dissociation constant (Kd1) of the control group was 2.57 +/- 0.33 nmol/L. When analgesia was induced by haloperidol or acupuncture, the Kd1 values decreased respectively (P < 0.05) to 1.44 +/- 0.03 nmol/L and 1.53 +/- 0.05 nmol/L. These Kd1 values further decreased to 1.25 +/- 0.03 nmol/L when acupuncture analgesia was potentiated by combined action of acupuncture and i.v. haloperidol (P < 0.01). In case of autoradiographic analysis of brain slices showed that the density of opioid receptors in many brain regions, such as N. Caudatus, preoptic lateral area, N. Paraventricularis, N. Centromedianus, Periaqueductal gray, showed significant increase, a results indicating that the upregulation of opioid receptors in rabbit brain may be one of the mechanisms in the potentiating action of haloperidol on acupuncture analgesia.

Chlorpromazine attenuated electroacupuncture analgesia in conscious rabbits.

By measuring the defense behavior in response to the noxious stimulation induced by potassium iontophoresis on ear-lobe skin of conscious rabbit, chlorpromazine (CPZ) (0.5 mg.kg-1, i.v.) induced hyperalgesia, whereas it significantly attenuated electroacupuncture analgesia (EAA) efficacy. Monoamines and their metabolites in cerebrospinal fluid (CSF) were measured by high pressure liquid chromatography with electrochemical detector (HPLC-ECD) while the attenuation effect of CPZ on EAA was observed. CPZ markedly enhanced 3,4-dihydroxyphenylacetic acid (DOPAC) (P < 0.05) and homovanillic acid (HVA) (P < 0.01) contents in CSF both in the presence and absence of electroacupuncture. CPZ attenuated EAA with elevations of either DOPAC or HVA concentrations in CSF. There was a positive correlation between the increase of DOPAC or HVA content in CSF and the attenuation effect of CPZ on EAA (P < 0.05). These results suggested that the activation of dopamine system was unfavorable for EAA.

Electroacupuncture reversed the inhibition of intestinal peristalsis induced by intrathecal injection of morphine in rabbits.

Morphine elicits a series of adverse effects including the inhibition of intestinal motility in addition to the therapeutic benefit of alleviating postoperative pain. To ascertain the role of electroacupuncture (EA) in diminishing those detrimental effects on recovery, we imitated the clinical procedures in rabbits. Morphine was given via a preimplanted cannula within spinal subarachnoid space, while the duodenal motility, respiration rate and arterial pressure were simultaneously recorded. It was found that morphine (6 mg/rabbit, IT) markedly suppressed duodenal peristalsis, decreased respiration rate throughout 90 min observation. When EA was administered together with morphine, peristalsis of the duodenum was much less inhibited (P < 0.05, vs morphine alone group), but no significant improvement of respiratory depression was noticed (P > 0.05), nor obvious change of arterial pressure in both groups. The results strongly recommend extensive application of EA in postoperative care, so as to decrease both the required dosage of morphine and the subsequent occurrence of postoperative ileus, while attaining sufficient analgesia.

[Effect of D1 and D2 dopamine receptor antagonists on acupuncture analgesia].

Some highly selective D1 or D2 receptor antagonists were tested on rabbit skin pain model to investigate the effect of the subtypes of dopamine receptor on acupuncture analgesia. It was found that iv. of D2 receptor antagonists haloperidol and clozapine, had a potentiating effect on acupuncture analgesia. Icv. of D2 receptor antagonists domperidone and sulpiride and D1 receptor antagonist SCH23390 also enhanced acupuncture analgesia markedly. The effect of D1 and D2 receptor on acupuncture analgesia was discussed.

C-fos expression during electroacupuncture analgesia in rats--an immunohistochemical study.

Although the central mechanisms of electroacupuncture analgesia (EAA) have been investigated, a systematic study for the involvement of neuronal populations of central nervous system (CNS) in EAA has not been well undertaken, largely due to the difficulty in tracing the neuronal pathways by traditional techniques. Recently developed c-fos expression examination by immunohistochemical method with Ab-1 antisera might be used for this purpose as a useful marker for neuronal activity in CNS. In this study, tail flick latency (TFL) was tested as an index of pain threshold in conscious rats. After unilateral electroacupuncture was applied at 'Zuan-san-li' and 'Huan-tiao', the TFL was significantly prolonged. To explore the possible involvement of certain neuronal groups of central nervous system in EAA, we examined the EAA accompanied c-fos expression throughout the neuraxis, and a lot of specific c-fos protein labelled neurons were found in lumbar spinal cord (laminae I and II), nucleus raphe magnus, nucleus raphe dorsalis, substantia grisea centralis, nucleus habenulae lateralis, nucleus habenulae medialis, nucleus medialis thalami, nucleus lateralis hypothalami, nucleus supramamillaris, nucleus supraopticus, nucleus arcuatus, nucleus preopticus medialis, nucleus amygdala, nucleus tractus diagonalis, etc. No obvious c-fos expression was shown in these areas on control rats. These results strongly suggested that the functional activation of above-mentioned nuclei by electroacupuncture was underlied in EAA action.

Effect of tiapride on electroacupuncture analgesia.

Tiapride icv 400 micrograms/rabbit exhibited analgesic and synergistic effects on electroacupuncture analgesia (EAA) in rabbits. Both electroacupuncture (EA) and tiapride (icv 400 micrograms/rabbit) enhanced the beta-endorphin-like immunoreactive substance (beta-EPIS) level in cerebrospinal fluid (CSF) measured by radioimmunoassay (RIA). When EA and tiapride were used in combination, a further increase of beta-EPIS content was found. The results suggested that promotion of beta-EPIS release by tiapride may be one of the mechanisms of synergistic effect of tiapride on EAA.

The attenuation effect of chlorpromazine on electro-acupuncture analgesia: involvement of dopamine system.

The effect of chlorpromazine (CPZ) (0.1 or 0.5 mg/kg, iv) on electroacupuncture analgesia (EAA) was examined by using potassium dolorimetry in rabbits. CPZ itself induced hyperanalgesia, whereas it attenuated EAA in terms of maximal increase of pain threshold as well as EAA after effect. Therefore, CPZ is not a good candidate for enhancing EAA in clinics. Monoamines and their metabolites in cerebrospinal fluid (CSF) of the rabbits were detected by high pressure liquid chromatography coupled to electrochemical detector (HPLC-ECD) method. It was revealed that CPZ enhanced DOPAC and HVA contents in CSF in both the presence and absence of electroacupuncture. CPZ attenuated EAA with elevations of DOPAC and HVA concentration in CSF. There was a positive correlation between the increases of DOPAC and HVA contents in CSF and attenuation effect of CPZ on EAA. These results suggested that activation of dopamine system be unfavorable for EAA.

Effect of combination of drugs with acupuncture on analgesic efficacy.

In rabbit experiments, some drugs used in clinics were selected and combined with electroacupuncture to observe the effect of drugs on acupuncture analgesia (AA). According to the effect of drugs on AA, the drugs were divided into three kinds: (1) Drugs with potentiating effect: fentanyl, pethidine, droperidol, perphenazine, metoclopramide, fenfluramine, tetrahydrocannabinol, fentanyl plus droperidol, fentanyl plus fenfluramine. (2) Drugs with reducing effect: ketamine and diazepam, (3) Drugs with no effect: sulpiride.