Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (SP), Brazil.
Epilepsy Behav. 2011 Oct;22(2):165-77. doi: 10.1016/j.yebeh.2011.06.028. Epub 2011 Aug 3.
The postictal state is generally followed by antinociception. It is known that connections between the dorsal raphe nucleus, the periaqueductal gray matter, and the locus coeruleus, an important noradrenergic brainstem nucleus, are involved in the descending control of ascending nociceptive pathways. The aim of the present study was to determine whether noradrenergic mechanisms in the locus coeruleus are involved in postictal antinociception. Yohimbine (an α(2)-receptor antagonist) or propranolol (a β-receptor antagonist) was microinjected unilaterally into the locus coeruleus, followed by intraperitoneal administration of pentylenetetrazole (PTZ), a noncompetitive antagonist that blocks GABA-mediated Cl(-) influx. Although the administration of both yohimbine and propranolol to the locus coeruleus/subcoeruleus area resulted in a significant decrease in tonic or tonic-clonic seizure-induced antinociception, the effect of yohimbine restricted to the locus coeruleus was more distinct compared with that of propranolol, possibly because of the presynaptic localization of α(2)-noradrenergic receptors in locus coeruleus neurons. These effects were related to the modulation of noradrenergic activity in the locus coeruleus. Interestingly, microinjections of noradrenaline into the locus coeruleus also decrease the postictal antinociception. The present results suggest that the mechanism underlying postictal antinociception involves both α(2)- and β-noradrenergic receptors in the locus coeruleus, although the action of noradrenaline on these receptors causes a paradoxical effect, depending on the nature of the local neurotransmission.
发作后状态通常伴随着镇痛。已知背缝核、导水管周围灰质和蓝斑之间的连接，蓝斑是一个重要的去甲肾上腺素能脑干核，参与上行伤害性通路的下行控制。本研究的目的是确定蓝斑内的去甲肾上腺素能机制是否参与发作后镇痛。育亨宾（α 2-受体拮抗剂）或普萘洛尔（β-受体拮抗剂）单侧注射到蓝斑，然后腹腔内给予戊四氮（PTZ），PTZ 是一种非竞争性拮抗剂，可阻断 GABA 介导的 Cl(-)内流。尽管育亨宾和普萘洛尔都注射到蓝斑/蓝斑下区，都会显著降低强直或强直-阵挛性癫痫发作引起的镇痛，但蓝斑内育亨宾的作用比普萘洛尔更明显，可能是因为蓝斑神经元中存在α 2-去甲肾上腺素能受体的突触前定位。这些作用与蓝斑内去甲肾上腺素能活性的调节有关。有趣的是，蓝斑内注射去甲肾上腺素也会降低发作后的镇痛。本研究结果表明，发作后镇痛的机制涉及蓝斑内的α 2-和β-去甲肾上腺素能受体，尽管去甲肾上腺素对这些受体的作用会产生一种矛盾的效应，这取决于局部神经传递的性质。
