Role of the types 1 and 2 receptors for Angiotensin II (AT1R/AT2R) in inflammation-induced nociceptor neuritogenesis

SERGIO BENITEZ; ALICIA SELTZER; DIEGO MESSINA; CRISTIAN ACOSTA

Córdoba

Congreso; XXXIII Congreso Anual SAN 2018; 2018

Sociedad Argentina de Investigación en Neurociencias

Types 1 and 2 receptors for Ang II (AT1R/AT2R) may play a role in neuropathic pain. Albeit Ang II induced neuritogenesis in primary sensory neurons has been offered as an explanation, the underlying mechanisms remain unknown. Our previous work showed that AT2R expressing neurons were C and A-δ nociceptors and that its expression increased in small neurons at CFA1, whereas at CFA4 increased only in medium neurons. Here we examined the expression pattern of AT1R during cutaneous induced inflammation. We used immunocytochemistry and selective AT1R and AT2R antagonists to examine their involvement in axonal growth and branching in normal and inflammatory conditions. We also tested in vivo neuritogenesis in IB4-nociceptors innervating the skin. In vitro, an inflammatory soup induced AT2R mRNA expression, while Ang II triggered TNF-α mRNA synthesis only when AT1R was blocked. Ang II promoted axonal growth and branching through both AT1R and AT2R. Their expressions correlated positively except when AT2R was inhibited. These suggest that the 2 receptors work together and are needed to sustain Ang II mediated neuritogenesis. In vivo, AT1R expression did not change with inflammation in nociceptors, but it did in large neurons at CFA4. 4 weeks treatment with antagonists against either AT1R or AT2R showed little impact on nociceptor neuritogenesis at skin level after inflammation. Thus, AT1R/AT2R seem to be required for the purported action of Ang II in the context of neuropathic pain.