Angiotensin (1–7) prevents angiotensin II ‐induced nociceptive behaviour via inhibition of p38 MAPK phosphorylation mediated through spinal M as receptors in mice

Background We have recently demonstrated that intrathecal (i.t.) administration of angiotensin II ( A ng II ) induces nociceptive behaviour in mice accompanied by a phosphorylation of p38 mitogen‐activated protein kinase ( MAPK ) mediated through A ng II type 1 ( AT 1 ) receptors. The N ‐terminal fragment of A ng II , A ng (1–7), plays a pivotal role in counterbalancing many of the well‐established actions induced by A ng II . However, the role of A ng (1–7) in spinal nociceptive transmission remains unclear. Therefore, we examined whether i.t. administration of A ng (1–7) can inhibit the A ng II ‐induced nociceptive behaviour in mice. Methods In the behavioural experiments, the accumulated response time of nociceptive behaviour consisting of scratching, biting and licking in conscious mice was determined during a 25‐min period starting after i.t. injection. The distribution and localization of AT 1 or M as receptors were analysed using a M ap A nalyzer and confocal microscope, respectively. Phosphorylation of p38 MAPK in the dorsal spinal cord was measured by Western blotting. Results The nociceptive behaviour induced by A ng II was dose‐dependently inhibited by the co‐administration of A ng (1–7). The inhibitory effect of A ng (1–7) was reversed by the co‐administration of A 779, a M as receptor antagonist. Western blot analysis showed that the increase in spinal p38 MAPK phosphorylation following the i.t. administration of A ng II was also inhibited by A ng (1–7), and the A ng (1–7) induced‐inhibition was prevented by A 779. Conclusions Our data show that the i.t. administration of A ng (1–7) attenuates an A ng II ‐induced nociceptive behaviour and is accompanied by the inhibition of p38 MAPK phosphorylation mediated through M as receptors.