孤束核参与刺激下丘脑室旁核的镇痛作用

本实验用电刺激鼠尾-嘶叫法测痛,观察电刺激下丘脑室旁核的镇痛效应,并采用核团损毁和核团内微量注射药物等方法分析其镇痛通路。实验结果如下:(1)电刺激下丘脑室旁核能产生明显的镇痛效应。同时,放射免疫测定发现脑干加压素含量升高。(2)损毁孤束核能取消刺激下丘脑室旁核的镇痛效应,但对基础痛阈无影响。(3)孤束核内微量注射加压素拮抗剂[d(CH_2)_5 TYr(Me)-AVP]60ng/0.6μl 和加压素抗血清0.6μl 都可明显对抗刺激下丘脑室旁核的镇痛效应。(4)直接在孤束核内微量注射加压素60ng/0.6μl,能模拟刺激下丘脑室旁核的镇痛效应。实验结果表明:电刺激下丘脑室旁核能产生镇痛效应,其机理之一可能是兴奋了下丘脑室旁核中加压素能神经元胞体,后者通过下行投射纤维在孤束核中释放加压素,影响孤束核神经元的活动,从而产生镇痛。     

刺激室旁核及加压素对大鼠胃缺血-再灌注损伤的保护作用

采用夹闭大鼠腹腔动脉30min,松开动脉夹血流复灌1h的胃缺血-再灌注损伤(gastric ischemia-reper-fusion injury,GI-RI）模型,观察了电或化学刺激室旁核（paraventricular nucleus,PVN）及外源性加压素（arginine-va-sopression,AVP）对GI-RI的影响,并对PVN的调控通路进行了初步分析。结果表明：电或化学刺激PVN后,GI-RI显著减轻;损毁双侧孤束核（nucleus tractus solitarius,NTS）或一侧NTS内注射AVP-V1受体阻断剂,均能取消电刺激PVN对GI-RI的效应;去除脑垂体后不影响PVN的作用;切断膈下迷走神经或切除腹腔交感神经节,则能加强电刺激PVN对GI-RI的影响;PVN内注射不同剂量的AVP同样能减轻大鼠GI-RI损伤。结果提示：PVN及AVP对大鼠GI-RI具有保护作用;PVN的这种作用可能是因电或化学刺激后,激活了其中的加压素能神经元,经其下行投射纤维释放AVP作用于NTS神经元的VAP-V1受体,并通过迷走和交感神经介导,从而影响GI-RI;而似与PVN-垂体通路关系不大。     

Arginine vasopressin in hypothalamic paraventricular nucleus is transferred to the caudate nucleus to participate in pain modulation

Arginine vasopressin (AVP), which is synthesized and secreted in the hypothalamic paraventricular nucleus (PVN), is the most important bioactive substance in the pain modulation. Our pervious study had shown that AVP plays an important role in pain modulation in caudate nucleus (CdN). The experiment was designed to investigate the source of AVP in CdN by the nucleus push-pull perfusion and radioimmunoassay. The results showed that: (1) pain stimulation increased the AVP concentration in the CdN perfusion liquid, (2) PVN decreased the effect of pain stimulation which was stronger in both sides than in one side of PVN cauterization; and (3) L-glutamate sodium would excited the PVN neurons by the PVN microinjection that could increase the AVP concentration in the CdN perfusion liquid. The data suggested that AVP in the CdN might come from the PVN in the pain process, i.e., AVP in the PVN might be transferred to the CdN to participate in the pain modulation.     

Arginine vasopressin in hypothalamic paraventricular nucleus is transferred to the nucleus raphe magnus to participate in pain modulation

Hypothalamic paraventricular nucleus (PVN) is one of the main sources of arginine vasopressin (AVP) synthesis and secretion. AVP is the most important bioactive substance in PVN regulating pain process. Our pervious study has pointed that pain stimulation induced AVP increase in the nucleus raphe magnus (NRM), which plays a role in pain modulation. The present study was designed to investigate the source of AVP in the rat NRM during pain process using the methods of nucleus push–pull perfusion and radioimmunoassay. The results showed that pain stimulation increased the AVP concentration in the NRM perfusion liquid, PVN cauterization inhibited the role that pain stimulation induced the increase of AVP concentration in the NRM perfusion liquid, and PVN microinjection of l-glutamate sodium, which excited the PVN neurons, could increase the AVP concentration in the NRM perfusion liquid. The data suggested that AVP in the PVN might be transferred to the NRM to participate in pain modulation.     

室旁核在刺激中脑防御反应区诱发防御性升压反应中的作用

雄性ＳＤ大鼠,用乌拉坦（７００ｍｇ／ｋｇ）和氯醛糖（３０ｍｇ／ｋｇ）腹腔麻醉。实验结果：（１）每隔５ｍｉｎ电刺激中脑导水管周围灰质背侧部“防御反应区”（ｄＰＡＧ）,持续观察５０ｍｉｎ,可见恒定的升压反应。若电解毁单侧室旁核（ＰＶＮ）区。１ｈ后,电刺激中脑ｄＰＡＧ区诱发的升压反应幅度部分减小。而损毁穹隆部、下丘脑前部、下丘脑背内侧核、下丘脑腹内侧核则无上述效应。（２）电刺激或微量注射高半胱胺酸（ＤＬ     

Median preoptic nucleus and subfornical organ drive renal sympathetic nerve activity via a glutamatergic mechanism within the paraventricular nucleus

The paraventricular nucleus (PVN) of the hypothalamus is involved in the neural control of sympathetic drive, but the precise mechanism(s) that influences the PVN is not known. The activation of the PVN may be influenced by input from higher forebrain areas, such as the median preoptic nucleus (MnPO) and the subfornical organ (SFO). We hypothesized that activation of the MnPO or SFO would drive the PVN through a glutamatergic pathway. Neuroanatomical connections were confirmed by the recovery of a retrograde tracer in the MnPO and SFO that was injected bilaterally into the PVN in rats. Microinjection of 200 pmol of N-methyl-d-aspartate (NMDA) or bicuculline-induced activation of the MnPO and increased renal sympathetic activity (RSNA), mean arterial pressure, and heart rate in anesthetized rats. These responses were attenuated by prior microinjection of a glutamate receptor blocker AP5 (4 nmol) into the PVN (NMDA - ΔRSNA 72 ± 8% vs. 5 ± 1%; P < 0.05). Using single-unit extracellular recording, we examined the effect of NMDA microinjection (200 pmol) into the MnPO on the firing activity of PVN neurons. Of the 11 active neurons in the PVN, 6 neurons were excited by 95 ± 17% (P < 0.05), 1 was inhibited by 57%, and 4 did not respond. The increased RSNA after activation of the SFO by ANG II (1 nmol) or bicuculline (200 pmol) was also reduced by AP5 in the PVN (for ANG II - ΔRSNA 46 ± 7% vs. 17 ± 4%; P < 0.05). Prior microinjection of ANG II type 1 receptor blocker losartan (4 nmol) into the PVN did not change the response to ANG II or bicuculline microinjection into the SFO. The results from this study demonstrate that the sympathoexcitation mediated by a glutamatergic mechanism in the PVN is partially driven by the activation of the MnPO or SFO.     

Elimination of vasopressin analgesia following lesions placed in the rat hypothalamic paraventricular nucleus

Pain thresholds are increased following central administration of arginine vasopressin (AVP), an effect which appears not to be mediated through opioid analgesic processes. In addition to magnocellular projections to the posterior lobe of the pituitary gland and parvocellular projections to the zona externa of the median eminence, the paraventricular nucleus (PVN) of the hypothalamus contains VP parvocellular neurons which also project to extrahypothalamic structures involved in pain inhibition. The present study examined whether AVP analgesia as measured by the tail-flick test was altered in animals with lesions placed in the PVN at either 7 or 35 days after surgery. VP levels in the pons-medulla and the lumbo-sacral spinal cord were measured by radioimmunoassay, as well as VP-like immunoreactivity in the PVN and spinal cord with immunocytochemistry. Lesions placed in the PVN eliminated AVP analgesia on the tail-flick test at both 7 and 35 days after surgery, and decreased radioimmunoassayable VP by 59% in the lumbo-sacral spinal cord and 36% in the pons-medulla. The extent of the lesions ranged from complete destruction of the PVN to partial sparing of ventro-medial PVN cells with VP-like immunoreactivity. These data indicate that the PVN is a critical structure for the integrity of AVP analgesia.     

Different signaling molecules responsible for IL-1beta-induced oxytocinergic and vasopressinergic neuron activation in the hypothalamic paraventricular nucleus of the rat

It has been well known that oxytocin (OT)-ergic and arginine vasopressin (AVP)-ergic neurons located in the hypothalamic paraventricular nucleus (PVN) and super optic nucleus (SON) are two kinds of neuroendocrine cells with diverse functions. It has also been demonstrated that immune stimuli can activate these neurons to secret OT and AVP. However, the intracellular signal transduction molecules responsible for the activation of these OT-ergic and AVP-ergic neurons in PVN by immune stimuli are still unclear. In this experiment, the roles of Fos, a protein product of immediate early gene c-fos, and extracellular signal-regulated protein kinase (ERK) 1/2, a signal transduction molecule of mitogen-activated protein kinase (MAPK) family, in these processes were studied in the PVN of the rat following IL-1beta stimulation. The Sprague-Dawley rats were received either 750 ng/kg IL-1beta or equal volume normal saline (NS) injection intravenously (i.v.), and perfused transcardially by 4% paraformaldehyde 3h later. Fos and phosphorylated ERK1/2 (pERK1/2)-immunoreactivity (-ir) was observed in PVN by ABC immunohistochemical staining. Meanwhile, the double staining for OT/Fos, AVP/Fos, OT/pERK1/2 and AVP/pERK1/2 were also processed. The ABC immunohistochemical staining results showed that after an i.v. injection of IL-1beta, the expressions of Fos and pERK1/2 increased evidently in the PVN. Double-staining results showed that a large number of OT-ir cells contained strong Fos-ir products in their nuclei, while only a few of OT cells were double labeled with pERK1/2. As to AVP neurons, great quantities of AVP cells were strongly double labeled with pERK1/2 while there were nearly no Fos-ir nuclei in AVP-ir cells. We conclude from these results that the intracellular IL-1beta-induced events in OT and AVP neurons in PVN are quite different. The OT neurons are mainly activated via Fos without involvement of ERK1/2 pathway, while the latter, but not Fos, involves the intracellular event in AVP neurons activated by IL-1beta.     

电刺激大鼠束旁核对底丘脑核和丘脑腹内侧核神经元的影响

本工作旨在探讨电刺激束旁核（parafascicular nucleus,PF）对帕金森病模型（Parkinson’s disease,PD）大鼠神经行为的改善作用及其机制。成年雄性Sprague—Dawley大鼠黑质致密部注射6一羟基多巴胺建立PD大鼠模型。采用行为学方法观察电刺激PF对阿朴吗啡诱发的大鼠旋转行为的作用,并应用在体细胞外记录法观察电刺激PF对大鼠底丘脑核（subthalamic nucleus,STN）及丘脑腹内侧核（ventromedial nucleus,VM）神经元放电的影响。结果发现,高频电刺激（130Hz,0．4mA,5s）PF一周,明显改善PD大鼠旋转行为。细胞外放电记录显示,高频电刺激PF使PD大鼠STN神经元自发放电减少,且该作用具有频率依赖性。另外,高频电刺激PF可使VM神经元兴奋,该作用也是频率依赖性的。我们在实验中同时观察到微电泳谷氨酸（glutamicacid,Glu）受体拮抗剂MK-801使STN神经元放电频率减少或完全抑制,微电泳t氨基丁酸（T-amino butyricacid,GABA）受体拮抗剂印防己毒素（picrotoxin,Pic）则使神经元放电频率增加。以上结果表明,GABA能和GIu能传入纤维可会聚于同-STN神经元,并对后者有紧张性作用。高频刺激PF,使该核团到STN神经元的Glu能兴奋性输出减少,导致STN的失活。这一作用通过基底神经节的间接通路,最终释放了丘脑运动核团VM的活性。高频刺激PF经PF,STN和VM的神经通路而改善PD大鼠神经行为。     

下丘脑室旁核加压素能神经元参与电针刺激对实验性...

It has been demonstrated in animal model of somatic pain that hypothalamic paraventricular nucleus (PVN) participates in acupuncture analgesia, probably by mediation of vasopressin release. The role of PVN in acupuncture analgesia for experimental visceral pain in rats was further investigated in the present study. Experimental results demonstrated that electroacupuncture could inhibit the writhing response, produced by intraperitoneal injection of antimonium potassium tartrate and this inhibitory effect could be enhanced by electrical stimulation of PVN, but decreased by electrolytical lesion of PVN, intracerebroventricular injection of vasopressin antiserum (14 microliters) or the vasopressin antagonist, d(CH2)5Tyr(Me)-AVP (500 ng/5 microliters). Intraperitoneal administration of the latter drug (10 micrograms/kg), however, was ineffective. The above experimental results suggest that vasopressinergic neurons in PVN also participate in the inhibition of visceral pain by electroacupuncture.