Effects of active components extracted from Dachuanxiong Decoction on the expressions of CGRP and its receptors in rats with migraine / 中成药

AIM To study the effects of active components extracted from Dachuanxiong Decoction (DCXD,Chuanxiong Rhizoma,Gastrodiae Rhizoma) on the expressions of calcitonin gene-related peptide (CGRP) and its receptors in hypothalamus and periaqueductal gray (PAG) of rats with migraine.METHODS Seventy-two rats were evenly assigned to six groups at random,normal group,model group,positive drug group,groups of highdose,middle-dose and low-dose DCXD.Each group was then divided into Subgroup A and Subgroup B.The migraine rat model was established by subcutaneous nitroglycerin injection.The expressions of CGRP in Subgroup B's rat hypothalamus and PAG were observed by immunohistochemical staining,while the levels of CGRP in rat plasma,hypothalamus and PAG in Subgroup A were detected by ELISA.All the gene expressions of CGRP and its receptors (CRLR,RCP,RAMP1) in Subgroup A's rat hypothalamus and PAG were assessed by real-time PCR.RESULTS There was a more significant CGRP level increase in plasma,hypothalamus and PAG in the model group than that in the normal group (P ＜ 0.01).The modelled rats found their up-regulated expressions of CGRP and RCP in hypothalamus (P ＜ 0.05),up-regulated expressions of CGRP and CRLR in PAG,and down-regulated expression of RCP (P ＜ 0.05).All low-dose,middle-dose,high-dose active components worked in decreasing the CGRP levels in plasma,hypothalamus and PAG.The middle-dose led to down-regulation of CGRP,RCP expressions in hypothalamus (P ＜0.05,P ＜0.01),down-regulation of CGRP,CRLR expressions in PAG (P ＜0.05),and up-regulation of RCP expression in PAG (P ＜ 0.05).CONCLUSION The mechanism of active components extracted from DCXD in migraine management may associate with its capability in down-regulating CGRP expressions in hypothalamus and PAG,reducing CGRP synthesis and inhibiting neurogenic inflammation.

Effect of Electroacupuncture on Expression of 5-HT7 Receptor in Periaqueductal Gray and Plasma Calcitonin Gene-related Peptide in Migraine Rats / 针刺研究

OBJECTIVE: To explore the analgesic effect of electroacupuncture(EA)by modulating 5-hydroxytryptamine 7 (5-HT7) receptor in periaqueductal gray (PAG) and plasma calcitonin gene-related peptide (CGRP). METHODS: Forty-two male Sprague Dawley (SD) rats were randomly divided into control，model and EA groups, 14 rat in each one. The neurogenic migraine model was established by repeated electrical stimulation on sagittal sinus duramater. Intracranial electrodes were used in the control group without stimuli. The rats in the EA group received EA (0.5－1 mA, 2 Hz/15 Hz) at "Fengchi" (GB 20) for 10 min after dural electrical stimulation, once a day for 6 days. The expression of 5-HT7 receptor in the PAG was assessed by immunofluorescence and Western blot, respectively; plasma CGRP was measured by radioimmunoassay. RESULTS: Compared with the control group, the positive neuron number and protein expression of 5-HT7 receptor in PAG and plasma CGRP increased after model establishment (all P<0.001). The above mentioned indexes were reversed in the EA group compared with those in the model group (the positive neuron number and protein expression of 5-HT7 receptor, P<0.01; plasma CGRP, P<0.05). CONCLUSIONS: EA at GB 20 can down-regulate the expression of 5-HT7 receptor in the PAG and reduce the content of plasma CGRP in the rats of migraine.

Influence of Electroacupuncture on Glu Concentration, GS and PAG Protein Levels in Striatum of Parkinson’s Disease Rats / 世界科学技术-中医药现代化

This study was aimed to explore the mechanism of electroacupuncture (EA) on improvement of Parkinson’s disease (PD). A total of 40 SD male rats were randomly divided into 4 groups, which were the normal group, sham-operation group, model group, and EA group (n=10). The 6-hydroxydopamine (6-OHDA) was used to prepare PD rat rotational model. The 0.2% Vitamin C of physiological saline was injected in the sham-operation group. EA on GV16-Fengfuand LR3-Taichongwas given for 30 min in the EA group after the model was successfully established, once a day, 7 days a treatment course. The treatment was given for 2 courses. Behavioral test was used to detect PD rat rotational behavior changes. Glu concentration in the striatum was detected by HPLC assay. The expression levels of GS and PAG were detected with western blot. The results showed that there were significant differences in the rotational behavior before and after treatment in the EA group (P < 0.01). Compared with the normal group and sham-operation group, Glu concentration significantly increased, GS expression obviously decreased, and PAG expression significantly increased in the model group (P < 0.01). Compared with the model group, Glu concentration obviously decreased (P < 0.05), GS expression significantly increased, and PAG significantly decreased in the EA group (P < 0.01). It was concluded that the protective effect of EA in PD may be associated with EA improving the expression of GS, reducing the expression of PAG, and relieving the cytotoxicity induced by Glu in the brain.

Morphine infusions into the rostrolateral periaqueductal gray affect maternal behaviors

It is well established that morphine inhibits maternal behaviors. Previous studies by our group have shown activation of the rostrolateral periaqueductal gray (rlPAG) upon inhibition-intended subcutaneous injections of morphine. In this context, we demonstrated that a single naloxone infusion into the rlPAG, following this opioid-induced inhibition, reactivated maternal behaviors. Since these data were obtained by using peripheral morphine injections, the present study was designed to test whether morphine injected directly into the rlPAG would affect maternal behaviors. Our hypothesis that morphine acting through the rlPAG would disrupt maternal behaviors was confirmed with a local infusion of morphine. The mothers showed shorter latency for locomotor behavior to explore the home cage (P = 0.049). Inhibition was especially evident regarding retrieving (P = 0.002), nest building (P = 0.05) and full maternal behavior (P = 0.023). These results support the view that opioidergic transmission plays a behaviorally meaningful inhibitory role in the rostrolateral PAG.

Role of nitric oxide in the periaqueductal gray in defensive behavior in mice: influence of prior local N-methyl-D-aspartate receptor activation and aversive condition

Glutamate N-methyl-D-aspartate (NMDA) receptor activation within the dorsal column of the periaqueductal gray (dPAG) leads to antinociceptive, autonomic, and behavioral responses characterized as the fear reaction. Activation of NMDA receptors in the brain increases nitric oxide (NO) synthesis, and NO has been proposed to be a mediator of the aversive action of glutamate. This paper reviews a series of studies investigating the effects of neuronal NO synthase (nNOS) inhibition in the dPAG of mice in different aversive conditions. nNOS inhibition by infusion of Nω-propyl-L-arginine (NPLA) prevents fear-like reactions (e.g., jumping, running, freezing) induced by NMDA receptor stimulation within the dPAG and produces anti-aversive effects when injected into the same midbrain site in mice confronted with a predator. Interestingly, nNOS inhibition within the dPAG does not change anxiety-like behavior in mice exposed to the elevated plus maze (EPM), but it reverses the effect of an anxiogenic dose of NMDA injected into the same site in animals subjected to the EPM. Altogether, the results support a role for glutamate NMDA receptors and NO in the dPAG in the regulation of defensive behaviors in mice. However, dPAG nitrergic modulation of anxiety-like behavior appears to depend on the magnitude of the aversive stimulus.

Modulation of Amygdalin on Glycine- and Glutamate-induced Ion Currents in Rat Periaqueductal Gray Neurons

Amygdalin is known as vitamain B17, and it was called laetrile. Amygdalin is composed of two molecules of glucose, one molecule of benzaldehyde which induces an analgesic action, and one molecule of hydrocyanic acid which is an anti-neoplastic compound. Amygdalin had been used to treat cancers and relieve pain. In order to evaluate whether the analgesic action of amygdalin is related with descending pain control system, we performed patch clamp study. In the present study, the modulatory effects of amygdalin on glycine- and glutamate-induced ion currents in periaqueductal gray (PAG) neurons were investigated using the nystatin-perforated patch clamp method. Continuous application of lipopolysaccharides (LPS) on PAG neurons resulted in increased glycine-induced ion current, and in decreased glutamate-induced ion current. In contrast, continuous application of amygdalin with LPS resulted in decreased glycine-induced ion current increased by LPS, and increased glutamate- induced ion current decreased by LPS in concentration- and time-dependent fashion. These results demonstrate that amygdalin modulates neuronal activity of PAG by modulation of glycine and glutamate. Based on the present results, it can be suggested that amygdalin participates in the regulation of the descending pain control system in the level of PAG neurons. The present study demonstrated that activation of the descending pain control system is one of the possible analgesic mechanisms of amygdalin.

Soporte nutricional en pacientes con pancreatitis aguda grave / Nutritional support in patients with severe acute pancreatitis

La pancreatitis aguda, especialmente en su forma grave, está asociada con una respuesta inflamatoria sistémica que lleva a un estado de hipermetabolismo e hipercatabolismo, en el que se requiere un excelente soporte nutricional que permita mantener la integridad estructural y la función de los órganos vitales con un estímulo mínimo de la secreción pancreática.La nutrición parenteral total era el soporte de elección, que permitía obtener todos los beneficios de la nutrición temprana sin estimular la secreción pancreática; pero la evidencia actual muestra mayores beneficios con la nutrición enteral, porque se asocia con menos complicaciones infecciosas y metabólicas y con disminución en los costos. Por ello las guías actuales de tratamiento de la pancreatitis aguda grave recomiendan como primera elección el soporte nutricional enteral.

Involvement of Sympathetic Nerve System in Vascular Headache / 中国康复理论与实践

@#Objective To investigate the involvement of sympathetic nerve system in the transmission of nociceptive information related to vascular headache. Methods Fos expression in the midbrain periaqueductal grey (PAG) induced by electrical stimulation of dural matter near the superior sagittal sinus (SSS) of the rat was determined before and after the extirpation of the superior cervical ganglion (SCG) using standard avidin-biotin immunohistochemistry. Results Fos immunoreactive positive neurons were detected in the ventrolateral PAG, and were bilateral symmetry. Fos expression was (133.3±12.5) in SCG extirpated group, and higher than that in sham-operated group (76.0±11.3). Conclusion The sympathetic system may be involved in the transmission of nociceptive information through PAG, associated with vascular headache such as migraine.

Changes of c-Fos Immunoreactivity in Midbrain by Deep Pain and Effects of Aspirin

PURPOSE: It had been suggested that pain arising from deep somatic body regions influences neural activity within periaqueductal gray(PAG) of midbrain via distinct spinal pathways. Aspirin is one of the popular non-steroidal anti-inflammatory drugs used in the management of pain. Fos expression was used as a marker for neuronal activity throughout central neurons following painful peripheral stimulation. This study was prepared to investigate changes of c-Fos immunoreactivity in midbrain by deep pain and effects of aspirin. METHODS: Male Sprague-Dawley rats were injected with 0.1 mL of 5% formalin in the plantar muscle of the right hindpaw. For experimental group II, aspirin was injected intravenously before injection of formalin. An aspirin-untreated group was utilized as group I. Rats were sacrificed at 0.5, 1, 2, 6 and 24 hours after formalin injection. Rat's brains were removed and sliced in rat brain matrix. Brain slices were coronally sectioned at interaural 1.00-1.36 mm. Serial sections were immunohistochemically reacted with polyclonal c-Fos antibody. The numbers of c-Fos protein immunoreactive neurons in ventrolateral periaqueductal gray(VLPAG) and dorsomedial periaqueductal gray(DMPAG) were counted and analyzed statistically with Mann-Whitney U tests. RESULTS: Higher numbers of c-Fos protein immunoreactive neurons were found in VLPAG. In both VLPAG and DMPAG of formalin-treated group, the numbers of c-Fos protein immunoreactive neurons were significantly higher at all time points than the formalin-untreated group, which peaked at two hours. The numbers of c-Fos immunoreactive neuron of the aspirin-treated group were less compared to the aspirin-untreated group at each time point. CONCLUSION: These results provide some basic knowledge in understanding the mechanism of formalin-induced deep somatic pain and the effects of aspirin.

Inhibitory Mechanism of Periaqueductal Gray Matter on Neuropathic Pain in Rat

OBJECTIVE: Using Lee et al (1996) model, we assessed the effect of opioid within the PAG on the manifestations of the neuropathic pain, and we studied the effects of naloxone on the analgesic effects of opioid. METHOD: Under pentobarbital anesthesia, male Sprague-Dawley rats were implanted with cannula in the ventral (n=10) and dorsal (n=6) PAG after the unilateral tibial and sural nerves were ligated and cut, leaving the common peroneal nerve intact. Pain sensitivity was assessed using the von Frey filament (8 mN) and acetone applied to the sensitive area for 1 week postoperatively. Rats with neuropathic pain were intracerebrally microinjected with DAMGO (0.1microgram/5microliter) and enkephaline (20microgram/5microliter) into the ventral and dorsal PAG and the pain sensitivity was assessed. Naloxone was injected to assess the observed change of pain sensitivity. RESULTS: Intracerebral microinjection of DAMGO and enkephaline into the ventral PAG, but not the dorsal PAG, increased the pain threshold which was reversed by naloxone. CONCLUSION: The results suggest that stimulation of the ventral PAG in neuropathic rats may reduce neuropathic pain via opioid-mediating pathway of the descending pain inhibition system.

A Case of Midbrain Hemorrhage Presenting as Bilateral Ptosis with Diurnal Fluctuation

A 54 year-old woman presented with bilateral fatigable blepharoptosis with diurnal fluctuation and diplopia for 10 days. She had a 3 year history of hypertension and showed symptoms of bilateral ptosis, supranuclear upward gaze palsy, and vertical diplopia with the pupils promptly constricting to light. Bell's phenomenon and vertical oculocephalic responses were intact but an impaired convergence was noted in both eyes. A intramuscular neostigmine test was negative. T1 and T2-wighted MRI of the brain showed a small round high signal intensity lesion in the periaqueductal gray (PAG) region. Therefore, she was diagnosed with a midbrain ptosis due to midbrain hemorrhage. The PAG lesion was suggested as contributing to the fatigable blepharoptosis and supranuclear upward gaze palsy in the patient. We recommend that patients with clinical features of myasthenia limited to the ocular muscles and, having risk factors for cerebrovascular disease, be thoroughly evaluated for intracranial lesions if warranted.

Exploration and Comparative Study on Mammography and MRI in Diagnosis of Breast Lesions after Breast Augmentation with PAG Injection / 实用放射学杂志

Objective To explore the value of mammography and MRI in the diagnosis of the breast lesions after breast augmentation with polyacrylamide gel(PAG) injection.Methods The mammographic and MRI findings of 26 patients with PAG augmentation mammoplasty retrospectively.Results The location and the form of PAG after augmentation mammoplasty could be detected by both mammography and MRI.The lesions in 4 cases with complications were detected by MRI but mammography.Conclusion MRI plays the more important role than mammography in the diagnosis of the complications or associated with breast lesions after augmentation mammoplasty with PAG.

THE INHIBITORY EFFECT OF STIMULATION IN PERIAQUEDUCTAL GREY ON NEURONS IN SPINAL DORSAL HORN AND ITS RELATION TO PAG-CDP / 西安交通大学学报(医学版)

The cord dorsum potential evoked by stimulation in the ventrolateral aspect of periaqueductal grey (PAG-CDP) was recorded from the dorsal surface of the spinal lumbosacral cord in rats. PAG stimulation with the same parameters as for producing PAG-CDP inhibited the C discharges of convergent neurons in spinal dorsal horn. There was a positive correlation between the time course of the inhibitory effect of PAG on convergent neurons and the duration of the slow wave of PAG-CDP. a positive correlation also presented between the latencies of the PAG inhibition and the slow wave. Furthermore, the PAG inhibition did not appear when the intensity of PAG stimulation was below the threshold of PAG-CDP. These results indicate that the presynaptic inhibition is involved in the PAG inhibition of the C discharges of convergent neurons in spinal dorsal horn.

GLIAL ACTIVATION AND PROINFLAMMATORY CYTOKINE EXPRESSION IN THE PERIAQUEDUCTAL GRAY INDUCED BY PERIPHERAL INFLAMMATORY PAIN / 解剖学报

Objective To observe the activation of astrocytes,microglia and expression of proinflammatory cytokines in the periaqueductal gray(PAG) by Complete Freunds Adjuvant(CFA)-induced inflammatory pain. Methods Heat hyperalgesia and mechanical allodynia were observed and the expressions of mRNA,protein of glial markers,and proinflammatory cytokines in the PAG were examined following intraplantar administration CFA in right hindpaw of the rat by behavioral testing,reverse transcription polymerase chain reaction(RT-PCR), Western blotting,and immunohistochemistry. Results CFA injection induced chronic thermal hyperalgesia and mechanical allodynia.After injection,the thermal hyperalgesia was recovered on Day 14,but the mechanical allodynia lasted more than 21 days.Microglial marker(Cluster of differentiation 14,CD14) and proinflammatory cytokines(Interleukinin-1?,tumor necrosis factor-?) showed a significant increase in their expression during all phases(acute,subacute and chronic) of inflammation.GFAP was observed only in PAG at subacute and chronic phases of inflammation.Conclusion The activation of microglia and astrocytes may be involved in the initiation and maintenance of inflammatory pain.Enhanced cytokines expression might play a role in eliciting behavioral hypersensitivity.

CEREBELLAR CORTICAL AFFERENTS FROM THE PERIAQUEDUCTAL GREY (PAG) IN THE RAT——A HRP STUDY / 解剖学报

A cerebellar afferent connection from the periaqueductal grey (PAG) has been demonstrated in the rat by means of retrograde transport of horseradish peroxidase (HRP) in the present study. The projection is bilateral, but the projection from the ipsilateral side is predominant (3:1). Its main origin is the ventromedial and ventrolateral regions of middle and caudal parts of PAG (98.8％), and the fibers reach different cerebellar cortical regions: culmen, declive, folium vermis, tuber vermis, pyramis vermis, uvula vermis, lobulus quadrangularis, crus Ⅰ, crus Ⅱ, and paraflocculus. Most labelled neurons are medium sized, but some small neurons also appear to project to cerebellum. Only a few large neurons are retrogradely labelled at the most caudal end of the caudal part. Functionally, both cerebellum and PAG are related to visceral activities. Consulting the present experiment, we discussed the significant role of the PAG-cerebellar projection.