Involvement of locus coeruleus noradrenergic neurons in supraspinal antinociception by α,β-methylene-ATP in rats
Involvement of locus coeruleus noradrenergic neurons in supraspinal antinociception by α,β-methylene-ATP in rats
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DOI：
10.1254/jphs.94.153
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发表时间：
2004-02-01
影响因子：
3.5
通讯作者：
Satoh, M
中科院分区：
文献类型：
--
作者：
Fukui, M;Takishita, A;Satoh, M
我们以前报道，脑室内（i. c. v.）P2 X受体激动剂的给药产生抗伤害感受作用，而β（2）肾上腺素能受体拮抗剂的i. c. v.预处理则减弱了这种作用。本研究探讨了大鼠蓝斑（LC）去甲肾上腺素能神经元参与P2 X受体激动剂α，β-亚甲基-ATP的脊髓上抗伤害作用。我们发现用DSP-4（50 mg/kg，i. p.）预处理，其是一种选择性破坏LC产生的去甲肾上腺素能神经元的神经毒素，显著减弱i. c. v.给药α，β-亚甲基-ATP（10 nmol/大鼠）的抗伤害感受。向双侧LC中微量注射α，β-亚甲基-ATP（0.1和1 nmol/侧）显著升高伤害性阈值，其作用强于10 nmol/大鼠剂量的i. c. v.给药。LC内注射α，β-亚甲基ATP（1 nmol/侧）的抗伤害性感受被磷酸吡哆醛-6-偶氮苯基-2 '，4'-二磺酸（1 nmol/侧）（一种非选择性P2 X受体拮抗剂）的共同注射显著减弱。这些结果表明，起源于LC的去甲肾上腺素能神经元通过LC的P2 X受体参与α，β-亚甲基-ATP的脊髓上抗伤害感受。
We reported previously that intracerebroventricular (i.c.v.) administration of P2X-receptor agonists produced antinociception and the effect was attenuated by i.c.v. pretreatment with beta(2)-adrenergic receptor antagonists. The present study examined the involvement of nor-adrenergic neurons arising from the locus coeruleus (LC) in the supraspinal antinociception by the P2X-receptor agonist alpha,beta-methylene-ATP in rats. We found that pretreatment with DSP-4 (50 mg/kg, i.p.), which is a neurotoxin to selectively disrupt noradrenergic neurons arising from the LC, significantly attenuated the antinociception by i.c.v. administration of alpha,beta-methylene-ATP (10nmol/rat). Microinjection of alpha,beta-methylene-ATP (0.1 and 1 nmol/side) into the bilateral LC significantly elevated the nociceptive threshold more potently than the i.c.v. administration at a dose of 10 nmol/rat. The antinociception by intra-LC injection of alpha,beta-methyleneATP (1 nmol/side) was significantly attenuated by co-injection of pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (1 nmol/side), a non-selective P2X-receptor antagonist. These results suggest that noradrenergic neurons arising from the LC are involved in the supraspinal antinociception by alpha,beta-methylene-ATP through P2X receptors in the LC.