The hyperalgesic effects induced by the injection of angiotensin II into the caudal ventrolateral medulla are mediated by the pontine A₅ noradrenergic cell group

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• 作者：José ; Marques-Lopes ; Dora Pinho ; Antó ; nio Albino-Teixeira ; Isaura Tavares
• 关键词：Descending pain modulation ; Angiotensin ; AT₁ receptor ; Noradrenaline ; Anti-dopamine β ; -hydroxylase-saporin ; Rat
• 刊名：Brain Research
• 出版年：2010
• 出版时间：14 April 2010
• 年：2010
• 卷：1325
• 期：Complete
• 页码：41-52
• 全文大小：1457 K

文摘

The caudal ventrolateral medulla (CVLM) is a key component of the supraspinal pain modulatory system. Pain modulation from the CVLM is partially relayed by spinally projecting noradrenergic neurons of the pontine A₅ cell group, which leave collateral fibres at the CVLM. The injection of angiotensin II (Ang II) into the CVLM was recently shown to induce hyperalgesia mediated by angiotensin type 1 (AT₁) receptors, expressed by CVLM neurons that do not project to the spinal cord. The present study evaluates the effects of lesioning the noradrenergic pontine A₅ cell group by the retrograde transport of the selective toxin anti-dopamine β-hydroxylase-saporin (anti-DBH-SAP) from the CVLM in pain behavioural responses elicited by Ang II injection into the CVLM. The injection of anti-DBH-SAP induced neurodegeneration, identified by the marker Fluoro-Jade B, restricted to the A₅ noradrenergic cell group. These results were confirmed by the decrease in the number of noradrenergic neurons only in the A₅ group. Pain behavioural evaluation using the formalin test showed that Ang II injection into the CVLM induced hyperalgesia, which was partially prevented by lesion of the A₅ noradrenergic cell group with anti-DBH-SAP. Immunostaining of AT₁ receptors in CVLM neurons retrogradely labelled from the A₅ noradrenergic cell group showed that CVLM neurons that project to the A₅ express AT₁ receptors, indicating that Ang II can modulate directly the CVLM-A₅ connection. The results show that Ang II-induced hyperalgesia elicited from the CVLM is mediated by an indirect pathway relayed at the pontine noradrenergic A₅ group.