Role of the Types 1 and 2 Receptors for Angiotensin II in Inflammation-Induced Nociceptor Neuritogenesis

ALICIA SELTZER; DIEGO MESSINA; CRISTIAN ACOSTA; SERGIO BENITEZ

Córdoba

Congreso; XXXIII Congress of the Argentine Society for Research in Neuroscience; 2018

Sociedad Argentina de Investigación en Neurociencias

Types 1 and 2 receptors for Ang II (AT1R/AT2R) may play arole in neuropathic pain. Albeit Ang II-induced neuritogenesis in primary sensory neurons has been offered as an explanation, the underlying mechanisms remain unknown. Ourprevious work showed that AT2R expressing neuronswere C and A-d nociceptors and that its expressionincreased in small neurons at CFA1, whereas at CFA4increased only in medium neurons. Here, we examined the expression pattern of AT1R during cutaneous-inducedinflammation. We used immunocytochemistry and selectiveAT1R and AT2R antagonists to examine their involvement inaxonal growth and branching in normal and inflammatoryconditions. We also tested in vivo neuritogenesis in IB4-nociceptors innervating the skin. In vitro, an inflammatory soupinduced AT2R mRNA expression, while Ang II triggeredTNF-a mRNA synthesis only when AT1R was blocked.Ang II promoted axonal growth and branching throughboth AT1R and AT2R. Their expressions correlated positively except when AT2R was inhibited. These suggest thatthe two receptors work together and are needed to sustainAng II-mediated neuritogenesis. In vivo, AT1R expression didnot change with inflammation in nociceptors, but it did inlarge neurons at CFA4. Four weeks treatment with antagonists against either AT1R or AT2R showed little impact onnociceptor neuritogenesis at skin level after inflammation.Thus, AT1R/AT2R seems to be required for the purportedaction of Ang II in the context of neuropathic pain.