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

European Journal of Pain - Tập 18 Số 10 - Trang 1471-1479 - 2014
Wataru Nemoto1, Yoshiki Ogata1, Osamu Nakagawasai1, Fukie Niijima1, Takeshi Tadano2, Koichi Tan–No1
1Department of Pharmacology, Tohoku Pharmaceutical University, Sendai, Japan
2Laboratory of Environmental and Health Sciences, College of Medical Pharmaceutical and Health Sciences, Kanazawa University, Japan

Tóm tắt

AbstractBackgroundWe have recently demonstrated that intrathecal (i.t.) administration of angiotensin II (Ang II) induces nociceptive behaviour in mice accompanied by a phosphorylation of p38 mitogen‐activated protein kinase (MAPK) mediated through Ang II type 1 (AT1) receptors. The N‐terminal fragment of Ang II, Ang (1–7), plays a pivotal role in counterbalancing many of the well‐established actions induced by Ang II. However, the role of Ang (1–7) in spinal nociceptive transmission remains unclear. Therefore, we examined whether i.t. administration of Ang (1–7) can inhibit the Ang II‐induced nociceptive behaviour in mice.MethodsIn 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 AT1 or Mas receptors were analysed using a MapAnalyzer and confocal microscope, respectively. Phosphorylation of p38 MAPK in the dorsal spinal cord was measured by Western blotting.ResultsThe nociceptive behaviour induced by Ang II was dose‐dependently inhibited by the co‐administration of Ang (1–7). The inhibitory effect of Ang (1–7) was reversed by the co‐administration of A779, a Mas receptor antagonist. Western blot analysis showed that the increase in spinal p38 MAPK phosphorylation following the i.t. administration of Ang II was also inhibited by Ang (1–7), and the Ang (1–7) induced‐inhibition was prevented by A779.ConclusionsOur data show that the i.t. administration of Ang (1–7) attenuates an Ang II‐induced nociceptive behaviour and is accompanied by the inhibition of p38 MAPK phosphorylation mediated through Mas receptors.

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European Journal of Pain

Tập 18 Số 10

1471-1479

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