Alterations in the rostral ventromedial medulla after the selective ablation of μ-opioid receptor expressing neurons.
Alterations in the rostral ventromedial medulla after the selective ablation of μ-opioid receptor expressing neurons.
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DOI：
10.1097/j.pain.0000000000000344
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发表时间：
2016-01
期刊：
影响因子：
7.4
通讯作者：
Meng ID
中科院分区：
文献类型：
--
作者：
Harasawa I;Johansen JP;Fields HL;Porreca F;Meng ID
延髓头端腹内侧区（RVM）对脊髓和延髓背角的伤害性感受神经元具有兴奋和抑制双重控制作用。选择性消融μ阿片受体（莫尔）表达的神经元在RVM使用皂草素共轭的莫尔激动剂皮吗啡-皂草素（derm-sap）减弱压力和损伤诱导的行为超敏反应，但RVM derm-sap的功能完整性的下行抑制系统和RVM神经元的属性仍然未知。已经描述了三类RVM神经元（on-cell、off-cell和中性细胞）对伤害性刺激和莫尔激动剂具有不同的反应。在轻度麻醉的大鼠中使用单单位记录，RVM神经元的特征在于在显微注射皮肤汁液或皂草素后。当与皂草素对照相比时，皮液处理导致on-cell和off-cell减少（P < 0.05）。中性细胞数量保持不变。经皮液处理后，RVM微量注射谷氨酸受体激动剂同型半胱氨酸增加甩尾潜伏期，而莫尔激动剂DAMGO则无影响。此外，电刺激中脑导水管周围灰质产生镇痛在皮肤汁液和皂草素控制具有相似的阈值。犬尿烯酸，谷氨酸受体拮抗剂，微量注射到RVM破坏中脑导水管周围灰质刺激产生的镇痛皂草素治疗和皮肤汁液治疗的大鼠。这些结果表明，在RVM中的MOR表达神经元是不需要的镇痛产生的直接或间接激活的神经元在RVM。
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.