Involvement of bradykinin, cytokines, sympathetic amines and prostaglandins in formalin-induced orofacial nociception in rats
Involvement of bradykinin, cytokines, sympathetic amines and prostaglandins in formalin-induced orofacial nociception in rats
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DOI：
10.1038/sj.bjp.0705724
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发表时间：
2004-04-01
影响因子：
7.3
通讯作者：
Zampronio, AR
中科院分区：
文献类型：
--
作者：
Chichorro, JG;Lorenzetti, BB;Zampronio, AR
1本研究通过评估各种治疗对行为伤害性反应的影响，描述了福尔马林注射到大鼠上唇引发的口面伤害性感受的一些机制和介质。（面部摩擦的持续时间）引起的低亚阈值，（即非伤害性的; 0.63%）或更高浓度的藻原（2.5%）。和前列腺素（PG）E-2（100 ng lip（-1））增强了对0.63%福尔马林的反应的两个阶段，而肿瘤坏死因子（TNF α; 5 pg lip（-1）），白细胞介素（IL）-1 β（0.5 pg lip（-1）），IL-6（2 ng lip（-1））和IL-8（200 pg lip（-1）），或间接作用的拟交感神经药物酪胺（200杯唇（-1）），每一个都只增加了伤害性感受的第二阶段。3相反，缓激肽（BK）B-2受体拮抗剂HOE 140可抑制2.5%福尔马林诱导的伤害性感受的两个阶段（5 μ g唇（-1））或选择性β（1）-肾上腺素受体拮抗剂阿替洛尔（100 μ g唇（-1））。然而，BK B-1受体拮抗剂des-Arg（9）-Leu（8）-BK（1和2 μ g lip（-1））、抗每种细胞因子的抗体和/或抗血清、肾上腺素能神经元阻滞剂乙啶（30 mg kg（-1）天（-1），s.c.，3天）和环氧合酶（考克斯）-2抑制剂塞来昔布（50和200 μ g唇（-1），皮下;或1和3 mg kg（-1），i. p.）只减少了反应的第二阶段。非选择性考克斯抑制剂吲哚美辛和5-脂氧合酶激活蛋白抑制剂MK 886没有改变福尔马林诱导的伤害感受。4我们的结果表明，BK，TNF-α，IL-1 β，IL-6，IL-8，交感胺和前列腺素（但不是白三烯）有助于显着福尔马林诱导的口面伤害性感受在大鼠和反应似乎更容易受到抑制B-2受体拮抗剂和选择性考克斯-2抑制剂比B-1受体拮抗剂或非选择性考克斯抑制剂更有效。
1 This study characterises some of the mechanisms and mediators involved in the orofacial nociception triggered by injection of formalin into the upper lip of the rat, by assessing the influence of various treatments on behavioural nociceptive responses (duration of facial rubbing) elicited either by a low subthreshold (i.e. non-nociceptive; 0.63%) or a higher concentration of the algogen (2.5%).2 The kininase II inhibitor captopril (5 mg kg(-1), s.c.) and prostaglandin( PG) E-2 (100 ng lip(-1)) potentiated both phases of the response to 0.63% formalin, whereas tumour necrosis factor (TNFalpha; 5 pg lip(-1)), interleukin(IL)-1beta (0.5 pg lip(-1)), IL-6 (2 ng lip(-1)) and IL-8 (200 pg lip(-1)), or the indirectly acting sympathomimetic drug tyramine (200 mug lip(-1)), each augmented only the second phase of nociception.3 Conversely, both phases of nociception induced by 2.5% formalin were inhibited by the bradykinin (BK) B-2 receptor antagonist HOE140 (5 mug lip(-1)) or the selective beta(1)-adrenoceptor antagonist atenolol (100 mug lip(-1)). However, the BK B-1 receptor antagonist des-Arg(9)-Leu(8)-BK (1 and 2 mug lip(-1)), antibody and/or antiserum against each of the cytokines, the adrenergic neurone blocker guanethidine (30 mg kg(-1) day(-1), s.c., for 3 days) and the cyclooxygenase(COX)-2 inhibitor celecoxib (50 and 200 mug lip(-1), s.c.; or 1 and 3 mg kg(-1), i.p.) reduced only the second phase of the response. The nonselective COX inhibitor indomethacin and the 5-lipoxygenase activating protein inhibitor MK886 did not change formalin-induced nociception.4 Our results indicate that BK, TNF-alpha, IL-1beta, IL-6, IL-8, sympathetic amines and PGs (but not leukotrienes) contribute significantly to formalin-induced orofacial nociception in the rat and the response seems to be more susceptible to inhibition by B-2 receptor antagonist and selective COX-2 inhibitor than by B-1 receptor antagonist or nonselective COX inhibitor.