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延髓开细胞和闭细胞在全身给药或向中脑导水管周围灰质微量注射安乃近(甲氨基苯甲酸钠)产生的抗伤害感受中的假定作用。

Putative role of medullary off- and on-cells in the antinociception produced by dipyrone (metamizol) administered systemically or microinjected into PAG.

作者信息

Tortorici Victor, Vanegas Horacio

机构信息

Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas 1020A Venezuela.

出版信息

Pain. 1994 May;57(2):197-205. doi: 10.1016/0304-3959(94)90224-0.

DOI:10.1016/0304-3959(94)90224-0
PMID:8090517
Abstract

Recent investigations have shown that non-steroidal antiinflammatory drugs (NSAIDs) may exert an antinociceptive effect when administered at or within the central nervous system (CNS). This might be due to the engagement of CNS substrates that support the analgesic effects of opiates, including the periaqueductal gray matter (PAG) and the rostral ventromedial medulla (RVM). The off- and on-cells of the RVM have been proposed to inhibit and facilitate, respectively, nociceptive transmission. Accordingly, upon heating of a rat's tail the tail-flick (TF) reflex occurs only after off-cells have decreased, and on-cells have increased, their activity. In the present study, i.v. administration (200 and 400 mg/kg) or PAG microinjection (25, 50, 100 and 250 micrograms) of dipyrone (metamizol) to lightly anesthetized rats caused a dose-related retardation of the heat-elicited off-cell pause, on-cell discharge and corresponding TF. Neuronal response and TF retained their mutual time relationship but shifted pari passu toward longer latencies. This antinociception was apparent already 5 min post-injection and reached a maximum in 50-60 min for i.v. administration and 30-35 min for PAG microinjection. These results confirm other authors' findings of the direct antinociceptive action of NSAIDs upon PAG, and provide the first evidence for a plausible involvement of RVM off- and on-cells in such antinociceptive effect.

摘要

最近的研究表明,非甾体抗炎药(NSAIDs)在中枢神经系统(CNS)给药时或在中枢神经系统内给药时可能发挥抗伤害感受作用。这可能是由于参与了支持阿片类药物镇痛作用的中枢神经系统底物,包括导水管周围灰质(PAG)和延髓头端腹内侧网状结构(RVM)。RVM的“开”细胞和“关”细胞分别被认为可以抑制和促进伤害性信息的传递。因此,在加热大鼠尾巴时,甩尾(TF)反射仅在“关”细胞活性降低且“开”细胞活性增加后才会发生。在本研究中,给轻度麻醉的大鼠静脉注射(200和400mg/kg)或向PAG微量注射(25、50、100和250μg)安乃近(甲氨基苯磺酸钠)会导致与剂量相关的热诱发的“关”细胞暂停、“开”细胞放电及相应TF的延迟。神经元反应和TF保留了它们相互的时间关系,但同时向更长的潜伏期转移。这种抗伤害感受在注射后5分钟就很明显,静脉注射在50 - 60分钟达到最大值,PAG微量注射在30 - 35分钟达到最大值。这些结果证实了其他作者关于NSAIDs对PAG有直接抗伤害感受作用的发现,并首次为RVM的“关”细胞和“开”细胞可能参与这种抗伤害感受作用提供了证据。

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Long-term Morphine-treated Rats are more Sensitive to Antinociceptive Effect of Diclofenac than the Morphine-naive rats.
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