表达μ-阿片受体的神经元被选择性切除后延髓头端腹内侧的变化。
Alterations in the rostral ventromedial medulla after the selective ablation of μ-opioid receptor expressing neurons.
作者信息
Harasawa Ichiro, Johansen Joshua P, Fields Howard L, Porreca Frank, Meng Ian D
机构信息
Department of Neurology, University of California, San Francisco, CA, USA RIKEN Brain Science Institute, Laboratory for Neural Circuitry of Memory, Saitama, Japan Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan Department of Pharmacology, College of Medicine, University of Arizona, Health Sciences Center, Tucson, AZ, USA Department of Biomedical Sciences, College of Osteopathic Medicine, and the Center for Excellence in the Neurosciences, University of New England, Biddeford, ME, USA.
出版信息
Pain. 2016 Jan;157(1):166-173. doi: 10.1097/j.pain.0000000000000344.
The rostral ventromedial medulla (RVM) exerts both inhibitory and excitatory controls over nociceptive neurons in the spinal cord and medullary dorsal horn. Selective ablation of mu-opioid receptor (MOR)-expressing neurons in the RVM using saporin conjugated to the MOR agonist dermorphin-saporin (derm-sap) attenuates stress and injury-induced behavioral hypersensitivity, yet the effect of RVM derm-sap on the functional integrity of the descending inhibitory system and the properties of RVM neurons remain unknown. Three classes of RVM neurons (on-cells, off-cells, and neutral cells) have been described with distinct responses to noxious stimuli and MOR agonists. Using single unit recording in lightly anesthetized rats, RVM neurons were characterized after microinjections of derm-sap or saporin. Derm-sap treatment resulted in a reduction in on-cells and off-cells when compared to saporin controls (P < 0.05). The number of neutral cells remained unchanged. After derm-sap treatment, RVM microinjections of the glutamate receptor agonist homocysteic acid increased tail-flick latencies, whereas the MOR agonist DAMGO had no effect. Furthermore, electrical stimulation of the periaqueductal gray produced analgesia in both derm-sap and saporin controls with similar thresholds. Microinjection of kynurenic acid, a glutamate receptor antagonist, into the RVM disrupted periaqueductal gray stimulation-produced analgesia in both saporin-treated and derm-sap-treated rats. These results indicate that MOR-expressing neurons in the RVM are not required for analgesia produced by either direct or indirect activation of neurons in the RVM.
延髓头端腹内侧区（RVM）对脊髓和延髓背角的伤害性神经元施加抑制性和兴奋性控制。使用与μ-阿片受体（MOR）激动剂皮啡肽-皂草素（derm-sap）偶联的皂草素对RVM中表达MOR的神经元进行选择性消融，可减轻应激和损伤诱导的行为超敏反应，但RVM derm-sap对下行抑制系统功能完整性和RVM神经元特性的影响仍不清楚。已描述了三类RVM神经元（开细胞、关细胞和中性细胞），它们对有害刺激和MOR激动剂有不同反应。在轻度麻醉的大鼠中使用单单位记录，在微量注射derm-sap或皂草素后对RVM神经元进行表征。与皂草素对照组相比，derm-sap处理导致开细胞和关细胞数量减少（P<0.05）。中性细胞数量保持不变。derm-sap处理后，向RVM微量注射谷氨酸受体激动剂高半胱氨酸可增加甩尾潜伏期，而MOR激动剂DAMGO则无作用。此外，对导水管周围灰质进行电刺激在derm-sap组和皂草素对照组中均产生了阈值相似的镇痛作用。向RVM微量注射谷氨酸受体拮抗剂犬尿氨酸可破坏导水管周围灰质刺激在皂草素处理组和derm-sap处理组大鼠中产生的镇痛作用。这些结果表明，RVM中表达MOR的神经元对于通过直接或间接激活RVM中的神经元所产生的镇痛作用并非必需。
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