反复电针对慢性痛的累加治疗作用及其机制研究

本研究从基础和临床两方面观察了反复电针对慢性痛的累加治疗作用,并结合疼痛患者及慢性痛动物模型中几种神经肽的放射免疫测定及相应受体拮抗剂的药理学研究结果,探讨了产生累加效应的可能机制。结果表明,在临床脊髓损伤性痉挛患者,１００Ｈｚ穴位体表电刺激有效地缓解痉挛并有累加效应;在临床慢性痛患者,２／１５Ｈｚ变频ＴＥＮＳ刺激有效地治疗疼痛并具有累加效应。在关节炎模型大鼠,电针刺激能产生明显的镇痛并具有累加效     

The Brain Effects of Laser Acupuncture in Healthy Individuals: An fMRI Investigation

Background

As laser acupuncture is being increasingly used to treat mental disorders, we sought to determine whether it has a biologically plausible effect by using functional magnetic resonance imaging (fMRI) to investigate the cerebral activation patterns from laser stimulation of relevant acupoints.

Methodology/Principal Findings

Ten healthy subjects were randomly stimulated with a fibreoptic infrared laser on 4 acupoints (LR14, CV14, LR8 and HT7) used for depression following the principles of Traditional Chinese Medicine (TCM), and 1 control non-acupoint (sham point) in a blocked design (alternating verum laser and placebo laser/rest blocks), while the blood oxygenation level-dependent (BOLD) fMRI response was recorded from the whole brain on a 3T scanner. Many of the acupoint laser stimulation conditions resulted in different patterns of neural activity. Regions with significantly increased activation included the limbic cortex (cingulate) and the frontal lobe (middle and superior frontal gyrus). Laser acupuncture tended to be associated with ipsilateral brain activation and contralateral deactivation that therefore cannot be simply attributed to somatosensory stimulation.

Conclusions/Significance

We found that laser stimulation of acupoints lead to activation of frontal-limbic-striatal brain regions, with the pattern of neural activity somewhat different for each acupuncture point. This is the first study to investigate laser acupuncture on a group of acupoints useful in the management of depression. Differing activity patterns depending on the acupoint site were demonstrated, suggesting that neurological effects vary with the site of stimulation. The mechanisms of activation and deactivation and their effects on depression warrant further investigation.     

汉字字形认知研究的刺激源设计及在fMRI研究中的应用

目的:评估汉字字形刺激源在汉字认知fMRI研究中的有效性,并对参与汉字处理的脑皮层区域进行定位及初步的量化分析。方法:选择母语为汉语、经利手测试后为右利手且裸眼视力正常(大于等于1．0)的在校大学生10例(男6例,女4例)作为被试。试验任务采用组块设计,将汉字(非字、假字、真字)投射到屏幕上,受试者接受汉字字形图片的视觉刺激,按非字-假字-真字-非字-假字-真字顺序呈现,共6个block。数据处理及统计分析采用国际通用的AFNI软件。结果:左额叶上、中、下回(包括Broca's area)、左中央前回(BA6)、左顶上小叶及顶下小叶(包括缘上回及角回)及双侧枕叶、楔前叶显著激活;左颞叶梭状回(BA37)、右额下回及双侧颞中、上回及扣带回显著激活,左大脑半球的激活体积明显大于右侧大脑半球。结论:本研究设计的汉字字形刺激源结合功能磁共振成像技术可以对汉字处理的相关大脑皮层区域进行定位,为研究人脑加工处理汉字的神经机制提供了一种有效的无创性影像学方法,并应用fMRI技术进一步证实其优势半球为左半球,且需要多种脑区共同参与完成。本试验模式可望成为一种对语言障碍病人进行脑功能检查的有效手段,从而为指导临床治疗和评价预后提供更丰富的信息。     

Neurophysiological correlates of acupuncture: limbic and thalamic responses to analgesic studies in non-human primates.

Single unit activity from chronically implanted squirrel monkeys was analyzed to evaluate the effect of acupuncture stimulation on limbic and thalamic structures associated with pain. Extracellular recordings and computer-generated interspike interval histograms (ISIH) were obtained from n. parafasicularis and n. ventralis posteromedialis of the thalamus and the laternal septum, basal amygdala and anterior cigulate cortex. Thalamic activity remained unchanged while limibc units demonstrated statistically significant alterations in both cell firing rate and the ISIH in response to acupuncture stimulation. Although pain thresholds in response to tooth pulp stimulation were increased by morphine (37-51% +/- 2.1), acupuncture proved totally ineffective. This may be interpreted as a selective response to acupuncture in CNS structures primarily concerned with the affective component of pain.     

Nitric Oxide-Mediated Modulation of Central Network Dynamics during Olfactory Perception

Nitric oxide (NO) modulates the dynamics of central olfactory networks and has been implicated in olfactory processing including learning. Land mollusks have a specialized olfactory lobe in the brain called the procerebral (PC) lobe. The PC lobe produces ongoing local field potential (LFP) oscillation, which is modulated by olfactory stimulation. We hypothesized that NO should be released in the PC lobe in response to olfactory stimulation, and to prove this, we applied an NO electrode to the PC lobe of the land slug Limax in an isolated tentacle-brain preparation. Olfactory stimulation applied to the olfactory epithelium transiently increased the NO concentration in the PC lobe, and this was blocked by the NO synthase inhibitor L-NAME at 3.7 mM. L-NAME at this concentration did not block the ongoing LFP oscillation, but did block the frequency increase during olfactory stimulation. Olfactory stimulation also enhanced spatial synchronicity of activity, and this response was also blocked by L-NAME. Single electrical stimulation of the superior tentacle nerve (STN) mimicked the effects of olfactory stimulation on LFP frequency and synchronicity, and both of these effects were blocked by L-NAME. L-NAME did not block synaptic transmission from the STN to the nonbursting (NB)-type PC lobe neurons, which presumably produce NO in an activity-dependent manner. Previous behavioral experiments have revealed impairment of olfactory discrimination after L-NAME injection. The recording conditions in the present work likely reproduce the in vivo brain state in those behavioral experiments. We speculate that the dynamical effects of NO released during olfactory perception underlie precise odor representation and memory formation in the brain, presumably through regulation of NB neuron activity.     

Long lasting effect of a single audiogenic seizure on GABA turnover rates and steady-state levels

GABA turnover rates (TOR) and steady-state levels (SSL) were determined, 16–18 h after a single acoustic stimulation, in 15 brain areas of 3 mouse sublines. Each subline differs in its response to an acoustic stimulation (Rb1 mice are clonic-tonic seizure-prone, Rb2: clonic seizure-prone, Rb3: seizure-resistant). TOR and SSL were compared to those of unstimulated control mice and to those of repeatedly stimulated mice of the same subline. Following a single acoustic stimulation long-lasting alterations of GABA metabolism, mainly large alterations of GABA TOR, are observed. Most of the effects elicited after repeated stimulations, either on SSL or TOR, are not those of the last stimulation and repeated seizures (and/or stimulations) strengthen the effect of a single one. It appears that, for each of the Rb sublines, a specific and quite simple profile of the alterations of GABA metabolism in response to a single or repeated audiogenic seizures (and/or stimulations) can be given. The global analysis through the correlation of GABA TOR and SSL gives an indication that the alterations of the parameters of the correlation observed are to be allocated to the audiogenic seizures. Furthermore the tonic and clonic components of the audiogenic seizures can be distinguished.     

核磁共振检测大鼠早期癫痫源性脑损伤的动态发展特征

为探讨癫痫源性脑损伤形成早期不同脑区病理改变和行为发作的动态发展特征 ,本研究对大鼠右背侧海马 (hippocampus,HPC)施加慢性强直电刺激 (6 0Hz,2s,0 .4～ 0 .6mA)诱发癫痫发作 ,1次 /d。每天记录大鼠原发性湿狗样抖动 (wetdogshakes,WEDS)频率 ,分别对大鼠施加电刺激 2、4、6、8和 10d后进行核磁共振成像 (T2 weightedmagneticresonanceimage ,T2 WI)检测 ,并对鼠脑进行了组织学切片鉴定。结果表明 :与空白对照组相比较 ,(1)施加 2d强直电刺激时 ,大鼠双侧背部侧脑室 (lateralventricle,LV)区域呈现对称性T2 WI信号绝对值增加 (n =4,左侧P =0 .0 0 18;右侧P =0 .0 0 10 ) ;施加 6d强直电刺激时 ,大鼠呈现植入电极对侧中、腹部LV区域T2 WI信号值增加 (n =5 ,P =0 .0 0 73;P =0 .0 2 49) ;施加 8d强直电刺激后 ,大鼠仅出现植入电极对侧腹部LV区域T2 WI信号值增加 (n =3,P =0 .0 34 0 ) ;施加 10d强直电刺激后 ,大鼠植入电极同侧腹部LV区域T2 WI信号值增加 (n =4,P =0 .0 10 7) ;(2 )随着强直电刺激天数增加 ,大鼠原发性WEDS频率高峰期出现在第 4个刺激日 ,然后WEDS频率下降 ,与T2 WI信号强度增加之间呈高度负相关关系 (相关系数r =- 0 .987,P <0 .0 2 ) ;(3)组织学切片鉴定 :T2 WI检测LV信号异     

Effects of repeated acupuncture action on pain sensitivity and beta-endorphin contents of the hypothalamus and midbrain of the rat

Changes in latencies (L) of nociceptive (NC) reactions of hot plate (HP) tail flick (TF) tests and dynamics of beta-endorphin (beta-ED) in hypothalamus and midbrain were studied in albino rats receiving 15 sessions of acupuncture (A) (20 min daily in bilateral Ho-Ku). It was shown that repeated A facilitated prolongation of LHP and LTF as compared to baseline and control levels. A decrease of the anti-NC systems capacity for activation in response to each A stimulation was observed. The dynamics of beta-endorphin in hypothalamus showed an opposite tendency as compared to that in midbrain. It is suggested that such a correlation of beta-ED activities in midbrain and hypothalamus might be one of the reasons for anti-NC mechanisms adaptation to A.     

Convergence of olfactory inputs from both antennae in the brain of the honeybee.

Electrical activities of the olfactory neurones in the brain of the honeybee were investigated. Odorous stimuli were given to each antenna separately or to both simultaneously. The inputs from the antennae affected both the impulse frequency and the latency of the olfactory interneurones in the protocerebrum. The predominant response was to the stimulation of the ipsilateral antenna. Input from the contralateral antenna produced mainly excitatory effects, although a few inputs gave inhibitory effects. No particular relationships between the loci of the units in the brain and the types of responses produced were found. Most of the units were located in the protocerebral lobe and in the central commissure. The units in the deutocerebrum responded only to the stimulation of the ipsilateral antenna, and the magnitude of response and the latency were not different with respect to unilateral or bilateral stimulation of the antennae. Differences in latency between unilateral and bilateral stimulation were observed in some of the units in the protocerebrum. Neural models which explain these phenomena are postulated.     

Effects of bilateral auricular acupuncture stimulation on body weight in healthy volunteers and mildly obese patients

We investigated the effects of auricular acupuncture stimulation on non-obese healthy volunteers and mildly obese patients. Subjects (n = 55 and 5, respectively) averaged 34.5 years old, and BMI was 24.3 and less than 27.5 kg/m2, respectively. We also studied the effects of single-blind sham treatment in approximately 500 age-, sex-, and BMI-matched subjects. Small (0.15 x 2.0 mm) auricular needles were placed intracutaneously into the bilateral cavum conchae identified by having a resistance of less than 100 kOmega/cm2. In the 2-week pretreatment the period, in which body weight was measured without auricular acupuncture stimulation, 57.1% of the subjects showed a reduction in body weight. This indicates that charting one's own body weight might itself be a useful method of weight control. In the auricular acupuncture treatment period, 35 healthy subjects of 55 (63.6%) showed a decreased body weight, 11 (20%) showed an increased body weight, and 9 (16.4%) showed no change in body weight. The obese patients showed individual variation, but all achieved weight reduction, with a highly significant correlation between body weight and fat volume. The CT/MRI cross-sectional pictures supported these findings. Sham treatment had no statistically significant effect on body weight. These results suggest that success in achieving weight reduction can be partly attributed to the act of charting of one's own weight pattern. Bilateral auricular acupuncture stimulation can help reduce body weight both in mildly obese patients and in healthy non-obese subjects. In conclusion, this is in accord with the bilateral auricular acupuncture stimulation that it may be useful in the treatment of the obesity. We propose a possible mechanism for the weight-reducing effects of bilateral auricular acupuncture stimulation.     

Decreased Peripheral and Central Responses to Acupuncture Stimulation following Modification of Body Ownership

Acupuncture stimulation increases local blood flow around the site of stimulation and induces signal changes in brain regions related to the body matrix. The rubber hand illusion (RHI) is an experimental paradigm that manipulates important aspects of bodily self-awareness. The present study aimed to investigate how modifications of body ownership using the RHI affect local blood flow and cerebral responses during acupuncture needle stimulation. During the RHI, acupuncture needle stimulation was applied to the real left hand while measuring blood microcirculation with a LASER Doppler imager (Experiment 1, N = 28) and concurrent brain signal changes using functional magnetic resonance imaging (fMRI; Experiment 2, N = 17). When the body ownership of participants was altered by the RHI, acupuncture stimulation resulted in a significantly lower increase in local blood flow (Experiment 1), and significantly less brain activation was detected in the right insula (Experiment 2). This study found changes in both local blood flow and brain responses during acupuncture needle stimulation following modification of body ownership. These findings suggest that physiological responses during acupuncture stimulation can be influenced by the modification of body ownership.     

Basis profile curve identification to understand electrical stimulation effects in human brain networks

Brain networks can be explored by delivering brief pulses of electrical current in one area while measuring voltage responses in other areas. We propose a convergent paradigm to study brain dynamics, focusing on a single brain site to observe the average effect of stimulating each of many other brain sites. Viewed in this manner, visually-apparent motifs in the temporal response shape emerge from adjacent stimulation sites. This work constructs and illustrates a data-driven approach to determine characteristic spatiotemporal structure in these response shapes, summarized by a set of unique “basis profile curves” (BPCs). Each BPC may be mapped back to underlying anatomy in a natural way, quantifying projection strength from each stimulation site using simple metrics. Our technique is demonstrated for an array of implanted brain surface electrodes in a human patient. This framework enables straightforward interpretation of single-pulse brain stimulation data, and can be applied generically to explore the diverse milieu of interactions that comprise the connectome.     

Effects of the removal of the orbito-frontal cortex on the development of reflex analgesia

The authors studied the effect of electric acupuncture stimulation (EAP) on the changes in pain thresholds prior to and after removal of the orbito-frontal cortex (OFC) of the brain in behavioral experiments on adult cats. Removal of OFC increased the thresholds of pain response at the 4th and the 5th levels of the conventional scale, reflecting emotionally-affective manifestations of pain, and intensified the effect of antinociceptive EAP. The results obtained are analysed in relation to the inhibitory tonic effect of OFC on antinociceptive structures of the brain. Different effects of OFC and somatosensory cortex on the antinociceptive structures of the brain are discussed.     

Modulation of Central Nociceptive Coding by Acupoint Stimulation

It is universally accepted that acupuncture or acupoint stimulation can produce analgesic effect on patients with painful disorders. The past decades has seen remarkable progress in exploring the central mechanisms of acupuncture-induced pain relief, including the neurotransmitter release and expression of particular receptors and genes in the spinal cord and the brain stem regions. Development of new techniques makes it possible to record and image the brain network patterns underlying pain perception and modulation, and to investigate the role of higher-level brain areas in mediating acupuncture analgesia. This review will present the current understanding of the neural network that is implicated in the modulation of pain by acupuncture. Special issue article in honor of Dr. Ji-Sheng Han.     

Inhibitory influences of vagal afferences on the oesophageal EMG peristaltic pattern

The influence of vagal afferents on the EMG peristaltic pattern was studied in pigeon oesophagus. Bilateral vagotomy did not abolish the primary peristalsis, but induced significant modifications of the peristaltic pattern parameters. Vagal afferent stimulation induced an inhibitory effect consisting of a temporary break or definitive block of the EMG peristaltic activity already in progress. Vagal afferent stimulation also induced a reduction of the spontaneous EMG activity and this effect was abolished either by glossopharyngeal bilateral section or ganglionic block. Likewise vagal afferent stimulation, the crop distension caused inhibitory effects on EMG peristaltic pattern. This effect was abolished by bilateral vagotomy. These results indicate that vagal afferents, originating from the crop, could influence the central neurons responsible for the peristaltic motor programme.     

Information processing in a cricket ganglion: The response of giant fibres to sound pulses

The response of giant fibres in the ventral nerve cord to stimulation of cercal afferents with pulses of sound was studied in the domestic cricket, Acheta domesticus. Pulses at 450 Hz gave the highest frequency response in several classes of units, and were therefore used as stimuli in subsequent experiments. In intact animals the response of the giant fibres to bilateral cercal stimulation showed a characteristic high frequency ‘on’ response followed by steady firing of some units for the duration of the sound pulse. The end of each pulse was followed by a short period of inhibition of the tonic units.Cercal amputation and other experiments showed that input from cercal afferents excites both large and small ipsilateral giants, and excites small and inhibits large contralateral giants. Descending input from higher neural centres in intact animals tends to reduce the responses to the stimuli. It is suggested that a function of the contralateral excitatory and inhibitory effects is to sharpen the ‘on’ response of the giant fibres to sound stimuli in intact animals.