Abstract
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 A 5 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 (AT 1) receptors, expressed by CVLM neurons that do not project to the spinal cord. The present study evaluates the effects of lesioning the noradrenergic pontine A 5 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 A 5 noradrenergic cell group. These results were confirmed by the decrease in the number of noradrenergic neurons only in the A 5 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 A 5 noradrenergic cell group with anti-DBH-SAP. Immunostaining of AT 1 receptors in CVLM neurons retrogradely labelled from the A 5 noradrenergic cell group showed that CVLM neurons that project to the A 5 express AT 1 receptors, indicating that Ang II can modulate directly the CVLM-A 5 connection. The results show that Ang II-induced hyperalgesia elicited from the CVLM is mediated by an indirect pathway relayed at the pontine noradrenergic A 5 group.
Published Version
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