Early and late onset of inflammation affects AT2R expression levels and subcellular localization in different subpopulations of nociceptors

BENITEZ, SERGIO; SELTZER, ALICIA; ACOSTA, CRISTIAN

Mar del Plata

Congreso; XXXII Congreso Anual SAN 2017; 2017

Sociedad Argentina de Investigación en Neurociencias

Pharmacological evidence suggests that the type 2 receptor for angiotensin II (AT2R) plays arole in relieving neuropathic pain, an effect that has been attributed to both inhibition (byEMA401) and activation (by mycolactone) of the receptor. Thus, more research is needed touncover the underlying mechanisms. We injected Complete Freund's Adjuvant (CFA) into thehindpaw of female Wistar rats and analyzed the effect 1 (CFA1) and 4 (CFA4) days thereafter.We combined immunohistochemistry with a detailed quantification analysis to examine a)subcellular localization and b) relative levels of AT2R. We found that AT2R was restricted toboth small and medium size dorsal root ganglion neurons that either bound IB4 or expressedTrkA or both. These markers indicated that AT2R expressing neurons were C and A-deltanociceptors. The intracellular localization of AT2R varied amongst the neurons. We observedtwo patterns: retracted to the peri-nuclear region or evenly distributed to the cell membrane.Membrane-associated staining is likely to reflect functional AT2R whereas cytoplasmicdistribution reflects receptor synthesis and availability. Hence, we measured both signals andcompare them across neuronal sizes. At CFA1 the receptor level increased significantly only atthe cell edge of small neurons, whereas at CFA4 AT2R levels increased only at the edge ofmedium neurons. This pattern could partly explain the dual behavior observed for AT2R inpathological pain models.