It was suggested that the nucleus submedius (Sm) in the medial thalamus and the ventrolateral orbital cortex (VLO) in the prefrontal cortex were involved not only in nociception, but also in modulation of nociception....It was suggested that the nucleus submedius (Sm) in the medial thalamus and the ventrolateral orbital cortex (VLO) in the prefrontal cortex were involved not only in nociception, but also in modulation of nociception. The Sm VLO PAG may constitute a pathway responsble for nociceptive modulation. Activation of this pathway depresses the nociceptive inputs at the spinal and trigeminal levels via the brainstem descending inhibitory system. This pathway may play an important role in analgesia produced by acupuncture evoked inputs from the small afferent fibers. For proving this hypothesis, a series of studies were performed in our laboratory.① Results of the present study revealed that bilateral electrolytic lesions of the Sm facilitated the radiant heat evoked tail flick (TF) reflex, with the latency of the TF reflex shortening in the rat lightly anesthetized with pentobarbital. If the Sm is purely a nociceptive center, the contrary result should be obtained. Therefore, this result suggests that Sm may be involved in nociceptive modulation, and may exert a tonic descending inhibitory influence on nociceptive transmission. Further investigations indicated that unilateral electrical stimulation of Sm or microinjection of glutamate into Sm significantly depressed the TF reflex, the jaw opening reflex (JOR), as well as the nociceptive responses of neurons in the spinal cord dorsal horn. All these effects were intensity (or dose) dependent and location specific. Moreover, the Sm evoked antinociception could be markedly reduced or eliminated by electrolytic lesion of ipsilateral VLO or bilateral lesions of ventrolateral or lateral parts of PAG, or by microinjection of GABA into VLO or PAG. Similarly, electrical or chemical activation of VLO also produced antinociception, and this effect was eliminated by lesion or depression of the PAG. These facts suggest that the antinociception produced by activation of Sm is mediated by VLO, leading to activation of the PAG brainstem descending inhibitory system and depression of the nociceptive inputs at the spinal and trigeminal levels. The Sm may be the only modulative center of nociception in the ventromedial thalamus, while the VLO may be the higher center of the pathway of nociceptive modulation consisting of Sm VLO PAG. Recent studies revealed that the Sm VLO PAG pathway may be also involved in modulation of the inflammatory hyperalgesia elicited by formalin. Electrical stimulation of the Sm could depresse the tonic nociceptive responses (agitation) elicited by subcutaneous injection of formalin into rat sole. Electrophysiological studies have demonstrated that on cell and off cell involved in the descending inhibitory modulation of nociception also exist in the Sm, suggesting that interaction of the two types of neurons in Sm may be the neuronal mechanisms. ② It was found that acupuncture manipulation and electroacupuncture (EA) stimulation with high intensity for activation of the fine afferent fibers in "acupoints" could activate the neurons in Sm, and markedly depressed the rat TF reflex and the nociceptive responses of neurons in the spinal cord dorsal horn. The antinociceptive effects produced by high intensity EA could be significantly attenuated by bilateral electrolytic lesions of Sm, or by microinjection of local anesthetic lidocaine into Sm. However, EA stimulation with low intensity for exciting only the large afferent fibers could not activate the Sm neurons, and the antinociceptive effects produced by such EA stimulation could not be affected by Sm or VLO lesions or application of lidocaine, but could be attenuated significantly by lidocaine application to the anterior pretectal nucleus (AptN). These facts suggest that antinociception produced by high intensity EA stimulation of "acupoints" is mediated by Sm VLO PAG system, but that produced by low intensity EA stimulation is not. This study also indicates that the acupuncture manipulation and high intensity EA are likely to act as noxious stimulation to elicit antinociception. ③ Microinjection of展开更多
腹外侧眶皮层(ventrolateral orbital cortex,VLO)是眶皮层的主要成分,它与导水管周围灰质(PAG)、丘脑和其它皮层之间有广泛的纤维联系。VLO不仅是一个痛觉感受中枢,而且也是一个痛觉调制中枢,通过激活PAG脑干下行抑制系统在脊髓和三叉...腹外侧眶皮层(ventrolateral orbital cortex,VLO)是眶皮层的主要成分,它与导水管周围灰质(PAG)、丘脑和其它皮层之间有广泛的纤维联系。VLO不仅是一个痛觉感受中枢,而且也是一个痛觉调制中枢,通过激活PAG脑干下行抑制系统在脊髓和三叉水平抑制伤害性信息的输入。研究还证实,阿片、5-HT和GABA等神经递质及其受体参与VLO的抗伤害效应。此外,VLO在针刺镇痛中也发挥重要作用。本文就腹外侧眶皮层在痛觉调制和针刺镇痛中的作用进行综述。展开更多
目的:观察腹外侧眶皮层(ventrolateral orbital cortex,VLO)内微量注射谷氨酸对大鼠后爪注射福尔马林诱发的腰段脊髓背角Fos表达的抑制效应以及该效应是否通过中脑导水管周围灰质(PAG)下行抑制系统介导。方法:免疫组织化学染色技术。结...目的:观察腹外侧眶皮层(ventrolateral orbital cortex,VLO)内微量注射谷氨酸对大鼠后爪注射福尔马林诱发的腰段脊髓背角Fos表达的抑制效应以及该效应是否通过中脑导水管周围灰质(PAG)下行抑制系统介导。方法:免疫组织化学染色技术。结果:(1)VLO内微量注射谷氨酸(100nmol/0.5μl)明显抑制大鼠后爪注射福尔马林诱发的脊髓背角Fos表达,与注射生理盐水相比,差异显著(P<0.001),并且这种抑制效应可被VLO内预先注射非选择性谷氨酸受体拮抗剂kynurenic acid(2nmol/0.5μl)所翻转,与单独注射谷氨酸相比差异显著(P<0.001),但与注射生理盐水相比无显著差异(P>0.05);(2)双侧腹外侧PAG内微量注射局麻剂利多卡因(0.2nmol/0.5μl)可以明显阻断VLO内微量注射谷氨酸(100nmol/0.5μl)对大鼠脊髓背角Fos表达的抑制效应,与单独注射谷氨酸相比差异显著(P<0.001),而双侧腹外侧PAG内微量注射生理盐水不影响VLO内微量注射谷氨酸对大鼠脊髓背角Fos表达的抑制效应(P>0.05)。结论:VLO内谷氨酸可能通过其受体激活PAG脑干下行抑制系统在脊髓水平抗炎性持续性伤害感受效应。展开更多
目的研究腹外侧眶皮层(ventrolateral orbital cortex,VLO)内微量注射sirtuin1(SIRT1)抑制剂EX527对吗啡诱导大鼠条件位置偏爱(conditioned place preference,CPP)的影响,并探讨CREB/BDNF通路在其中的作用。方法应用脑立体定位术在大鼠...目的研究腹外侧眶皮层(ventrolateral orbital cortex,VLO)内微量注射sirtuin1(SIRT1)抑制剂EX527对吗啡诱导大鼠条件位置偏爱(conditioned place preference,CPP)的影响,并探讨CREB/BDNF通路在其中的作用。方法应用脑立体定位术在大鼠双侧VLO内留置导管,建立吗啡诱导大鼠CPP模型,d 1为适应,d 2~4为前测,d 5~14为条件性训练,隔日交替腹腔注射吗啡(1 mL·kg^(-1),5 mg·kg^(-1))或生理盐水(1 mL·kg^(-1)),提前30 min通过导管向双侧VLO内微量注射EX527(1μL,5 g·L^(-1))或DMSO(1%,1μL),d 15为测试。CPP测试后立即取脑分离VLO组织,Western blot检测VLO内SIRT1、PSD95、c-fos、p-ERK、CREB、BDNF的表达水平。结果吗啡诱导大鼠CPP模型构建成功,吗啡诱导CPP形成组VLO内SIRT1、PSD95、c-fos、p-ERK、CREB蛋白表达明显增高(P<0.05),BDNF蛋白表达明显降低(P<0.05)。VLO内微量注射EX527抑制了吗啡诱导大鼠CPP形成,且明显降低了VLO内SIRT1、PSD95、c-fos、p-ERK、CREB、BDNF蛋白表达(P<0.05)。结论EX527通过抑制吗啡引起的VLO内SIRT1及其下游相关分子表达的增高,并进一步降低BDNF表达,从而有效阻断了大鼠吗啡成瘾的形成。展开更多
文摘It was suggested that the nucleus submedius (Sm) in the medial thalamus and the ventrolateral orbital cortex (VLO) in the prefrontal cortex were involved not only in nociception, but also in modulation of nociception. The Sm VLO PAG may constitute a pathway responsble for nociceptive modulation. Activation of this pathway depresses the nociceptive inputs at the spinal and trigeminal levels via the brainstem descending inhibitory system. This pathway may play an important role in analgesia produced by acupuncture evoked inputs from the small afferent fibers. For proving this hypothesis, a series of studies were performed in our laboratory.① Results of the present study revealed that bilateral electrolytic lesions of the Sm facilitated the radiant heat evoked tail flick (TF) reflex, with the latency of the TF reflex shortening in the rat lightly anesthetized with pentobarbital. If the Sm is purely a nociceptive center, the contrary result should be obtained. Therefore, this result suggests that Sm may be involved in nociceptive modulation, and may exert a tonic descending inhibitory influence on nociceptive transmission. Further investigations indicated that unilateral electrical stimulation of Sm or microinjection of glutamate into Sm significantly depressed the TF reflex, the jaw opening reflex (JOR), as well as the nociceptive responses of neurons in the spinal cord dorsal horn. All these effects were intensity (or dose) dependent and location specific. Moreover, the Sm evoked antinociception could be markedly reduced or eliminated by electrolytic lesion of ipsilateral VLO or bilateral lesions of ventrolateral or lateral parts of PAG, or by microinjection of GABA into VLO or PAG. Similarly, electrical or chemical activation of VLO also produced antinociception, and this effect was eliminated by lesion or depression of the PAG. These facts suggest that the antinociception produced by activation of Sm is mediated by VLO, leading to activation of the PAG brainstem descending inhibitory system and depression of the nociceptive inputs at the spinal and trigeminal levels. The Sm may be the only modulative center of nociception in the ventromedial thalamus, while the VLO may be the higher center of the pathway of nociceptive modulation consisting of Sm VLO PAG. Recent studies revealed that the Sm VLO PAG pathway may be also involved in modulation of the inflammatory hyperalgesia elicited by formalin. Electrical stimulation of the Sm could depresse the tonic nociceptive responses (agitation) elicited by subcutaneous injection of formalin into rat sole. Electrophysiological studies have demonstrated that on cell and off cell involved in the descending inhibitory modulation of nociception also exist in the Sm, suggesting that interaction of the two types of neurons in Sm may be the neuronal mechanisms. ② It was found that acupuncture manipulation and electroacupuncture (EA) stimulation with high intensity for activation of the fine afferent fibers in "acupoints" could activate the neurons in Sm, and markedly depressed the rat TF reflex and the nociceptive responses of neurons in the spinal cord dorsal horn. The antinociceptive effects produced by high intensity EA could be significantly attenuated by bilateral electrolytic lesions of Sm, or by microinjection of local anesthetic lidocaine into Sm. However, EA stimulation with low intensity for exciting only the large afferent fibers could not activate the Sm neurons, and the antinociceptive effects produced by such EA stimulation could not be affected by Sm or VLO lesions or application of lidocaine, but could be attenuated significantly by lidocaine application to the anterior pretectal nucleus (AptN). These facts suggest that antinociception produced by high intensity EA stimulation of "acupoints" is mediated by Sm VLO PAG system, but that produced by low intensity EA stimulation is not. This study also indicates that the acupuncture manipulation and high intensity EA are likely to act as noxious stimulation to elicit antinociception. ③ Microinjection of
文摘腹外侧眶皮层(ventrolateral orbital cortex,VLO)是眶皮层的主要成分,它与导水管周围灰质(PAG)、丘脑和其它皮层之间有广泛的纤维联系。VLO不仅是一个痛觉感受中枢,而且也是一个痛觉调制中枢,通过激活PAG脑干下行抑制系统在脊髓和三叉水平抑制伤害性信息的输入。研究还证实,阿片、5-HT和GABA等神经递质及其受体参与VLO的抗伤害效应。此外,VLO在针刺镇痛中也发挥重要作用。本文就腹外侧眶皮层在痛觉调制和针刺镇痛中的作用进行综述。
文摘目的:观察腹外侧眶皮层(ventrolateral orbital cortex,VLO)内微量注射谷氨酸对大鼠后爪注射福尔马林诱发的腰段脊髓背角Fos表达的抑制效应以及该效应是否通过中脑导水管周围灰质(PAG)下行抑制系统介导。方法:免疫组织化学染色技术。结果:(1)VLO内微量注射谷氨酸(100nmol/0.5μl)明显抑制大鼠后爪注射福尔马林诱发的脊髓背角Fos表达,与注射生理盐水相比,差异显著(P<0.001),并且这种抑制效应可被VLO内预先注射非选择性谷氨酸受体拮抗剂kynurenic acid(2nmol/0.5μl)所翻转,与单独注射谷氨酸相比差异显著(P<0.001),但与注射生理盐水相比无显著差异(P>0.05);(2)双侧腹外侧PAG内微量注射局麻剂利多卡因(0.2nmol/0.5μl)可以明显阻断VLO内微量注射谷氨酸(100nmol/0.5μl)对大鼠脊髓背角Fos表达的抑制效应,与单独注射谷氨酸相比差异显著(P<0.001),而双侧腹外侧PAG内微量注射生理盐水不影响VLO内微量注射谷氨酸对大鼠脊髓背角Fos表达的抑制效应(P>0.05)。结论:VLO内谷氨酸可能通过其受体激活PAG脑干下行抑制系统在脊髓水平抗炎性持续性伤害感受效应。
