Cornea-responsive medullary dorsal horn neurons: Modulation by local opioids and projections to thalamus and brain stem
Cornea-responsive medullary dorsal horn neurons: Modulation by local opioids and projections to thalamus and brain stem
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DOI：
10.1152/jn.2000.84.2.1050
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发表时间：
2000-08-01
影响因子：
2.5
通讯作者：
Bereiter, DA
中科院分区：
文献类型：
--
作者：
Hirata, H;Takeshita, S;Bereiter, DA
在此之前，研究人员确定在尾侧亚核尾侧注射吗啡可以模拟静脉注射吗啡对内插/尾侧亚核（Vi/Vc）过渡区记录的角膜反应神经元的促进作用。本研究的目的是确定介导角膜单位调节的阿片受体亚型，并确定阿片药物是否影响特定类别的单位。在巴比妥酸麻醉的雄性大鼠角膜上施加CO2气体脉冲，以刺激Vi/Vc（“吻侧”神经元）和尾侧/上颈脊髓过渡区（Vc/C1，“尾侧”神经元）的神经元。在尾侧过渡区微量注射硫酸吗啡（2.9-4.8 nmol）或选择性受体激动剂D-Ala， N-Me-Phe, Gly-ol-enkephalin （DAMGO; 1.8-15.0 pmol）可增强27个吻侧单位中7个（26%）对CO2脉冲的反应，抑制10个单位（37%）的反应。选择性δ {[D-Pen(2,5)] （DPDPE）显微注射；24- 30pmol}或kappa受体激动剂（U50488; 1.8-30.0 pmol）进入尾侧过渡区不影响吻侧单位的co2诱发反应。尾端细胞受到局部DAMGO或DPDPE的抑制，但u50、488h不受影响。纳洛酮（0.2 mg/kg iv）可逆转DAMGO和DPDPE的作用。15个单位中，静脉注射吗啡对co2诱发活性的影响有3个与局部DAMGO方向相反，4个单位与局部DAMGO方向相同但幅度更大，8个单位与局部DAMGO方向相同但幅度更大。对二氧化碳有反应的吻侧和尾侧单元投射到丘脑后核/无椎带区（PO/ZI）或上唾液腺/面神经核区（SSN/VII）。然而，对CO2脉冲无响应的吻侧单位仅预测SSN/VII，对CO2无响应的尾侧单位仅预测PO/ZI。我们得出结论，阿片镇痛在角膜疼痛中的回路涉及多个作用位点：尾侧过渡区神经元的抑制，通过亚核间连接调节吻侧单位，以及脊柱上部位。局部使用阿片类激动剂可调节所有类型的角膜单位。角膜刺激方式可预测鼻侧和尾侧单元对感觉丘脑和脑干反射区的传出投射状态。
Previously, it was determined that microinjection of morphine into the caudal portion of subnucleus caudalis mimicked the facilitatory effects of intravenous morphine on cornea-responsive neurons recorded at the subnucleus interpolaris/caudalis (Vi/Vc) transition region. The aim of the present study was to determine the opioid receptor subtype(s) that mediate modulation of corneal units and to determine whether opioid drugs affected unique classes of units. Pulses of CO2 gas applied to the cornea were used to excite neurons at the Vi/Vc ("rostral" neurons) and the caudalis/upper cervical spinal cord transition region (Vc/C1, "caudal" neurons) in barbiturate-anesthetized male rats. Microinjection of morphine sulfate (2.9-4.8 nmol) or the selective mu receptor agonist D-Ala, N-Me-Phe, Gly-ol-enkephalin (DAMGO; 1.8-15.0 pmol) into the caudal transition region enhanced the response in 7 of 27 (26%) rostral units to CO2 pulses and depressed that of 10 units (37%). Microinjection of a selective delta {[D-Pen(2,5)] (DPDPE); 24-30 pmol} or kappa receptor agonist (U50488; 1.8-30.0 pmol) into the caudal transition region did not affect the CO2-evoked responses of rostral units. Caudal units were inhibited by local DAMGO or DPDPE but were not affected by U50,488H. The effects of DAMGO and DPDPE were reversed by naloxone (0.2 mg/kg iv). Intravenous morphine altered the CO2-evoked activity in a direction opposite to that of local DAMGO in 3 of 15 units, in the same direction as local DAMGO but with greater magnitude in 4 units, and in the same direction with equal magnitude as local DAMGO in 8 units. CO2-responsive rostral and caudal units projected to either the thalamic posterior nucleus/zona incerta region (PO/ZI) or the superior salivatory/facial nucleus region (SSN/VII). However, rostral units not responsive to CO2 pulses projected only to SSN/VII and caudal units not responsive to CO2 projected only to PO/ZI. It was concluded that the circuitry for opioid analgesia in corneal pain involves multiple sites of action: inhibition of neurons at the caudal transition region, by intersubnuclear connections to modulate rostral units, and by supraspinal sites. Local administration of opioid agonists modulated all classes of corneal units. Corneal stimulus modality was predictive of efferent projection status for rostral and caudal units to sensory thalamus and reflex areas of the brain stem.