Tortorici V, Vanegas H
Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Venezuela.
Eur J Neurosci. 1995 Sep 1;7(9):1857-65. doi: 10.1111/j.1460-9568.1995.tb00706.x.
Previous experiments using metamizol have shown that this non-steroidal anti-inflammatory drug (NSAID) produces a central anti-nociceptive effect probably through neural substrates that also support the analgesic effects of opiates, such as the periaqueductal grey matter (PAG) and the off- and on-cells of the rostral ventromedial medulla (RVM). Off- and on-cells have been postulated to respectively inhibit and facilitate nociceptive transmission, since the heat-elicited tail flick reflex (TF) occurs only after off-cells have decreased (pause), and on-cells, have increased (burst) their activity. The aim of the present study was to examine whether the effect of metamizol upon TF and off- and on-cells responses could be generalized to other NSAIDs such as, in this case, lysine-acetylsalicylate (LASA). Fifty-nine off- and on-cells of the RVM were recorded in lightly anaesthetized rats. Systemic administration (200 and 300 mg/kg) or PAG microinjection (30, 50 and 100 micrograms) of LASA caused retardation of the heat-elicited off-cell pause, on-cell burst and the corresponding TF. Neuronal responses and TF retained their mutual time relationship but shifted simultaneously toward longer latencies. This anti-nociceptive effect of LASA was dose-dependent, present 5 min after administration and reached a maximum in 30 min for both administration methods. These data confirm that analgesics typically defined as peripherally-acting, such as metamizol and LASA in this study, may also have an anti-nociceptive effect by acting directly upon PAG, and suggest that this central effect involves the RVM off- and on-cells.
以往使用安乃近的实验表明，这种非甾体抗炎药（NSAID）可能通过与支持阿片类药物镇痛作用相同的神经基质产生中枢性抗伤害感受作用，这些神经基质包括导水管周围灰质（PAG）以及延髓头端腹内侧（RVM）的off细胞和on细胞。由于热刺激引起的甩尾反射（TF）仅在off细胞活动减少（暂停）且on细胞活动增加（爆发）后才会出现，因此推测off细胞和on细胞分别抑制和促进伤害性感受传递。本研究的目的是检验安乃近对TF以及off细胞和on细胞反应的影响是否也适用于其他非甾体抗炎药，如在本研究中的赖氨酸乙酰水杨酸（LASA）。在轻度麻醉的大鼠中记录了59个RVM的off细胞和on细胞。全身给药（200和300mg/kg）或向PAG微量注射（30、50和100μg）LASA会导致热刺激引起的off细胞暂停、on细胞爆发以及相应的TF延迟。神经元反应和TF保持其相互的时间关系，但同时向更长的潜伏期偏移。LASA的这种抗伤害感受作用是剂量依赖性的，给药后5分钟出现，两种给药方法均在30分钟时达到最大值。这些数据证实，通常被定义为外周作用的镇痛药，如本研究中的安乃近和LASA，也可能通过直接作用于PAG产生抗伤害感受作用，并表明这种中枢作用涉及RVM的off细胞和on细胞。
