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Inflammation Research

, Volume 44, Issue 11, pp 470–474 | Cite as

Involvement of substance P as a mediator in capsaicin-induced mouse ear oedema

  • H. Inoue
  • N. Nagata
  • Y. Koshihara
Article

Abstract

We examined the involvement of substance P (SP) in mouse ear oedema induced by topical application of capsaicin (250 µg/ear). Reapplication of capsaicin at 4h, 24h, and 48h after initial treatment did not induce a second oedema response. Oedema induced after the second application was significantly (p<0.01 orp<0.001) suppressed for up to 30 days but was observed when capsaicin was applied 40 days after initial treatment. Topical pretreatment of ears with capsaicin at 4h, 24h and 48h before i.v. injection of SP (5 µg/kg) did not cause a significant inhibition of plasma extravasation in ear skin. NK1 receptor antagonists such as RP 67580 (ED50:0.19 mg/kg, i.v.), spantide II (ED50:0.33 mg/kg, i.v.), and GR 82334 (ED50:0.26 mg/kg, i.v.), inhibited capsaicin-induced ear oedema, whereas SR 48968 (2.0 mg/kg, i.v.), a NK2 receptor antagonist, had no effect. Furthermore, RP 67580 (0.5 kg/mg, i.v.) inhibited the oedema response induced by reapplication of capsaicin at 50 days after initial treatment. These results indicate that tachyphylaxis of capsaicin-induced oedema is reversible and suggest that this response may be due mainly to a reduction of SP in sensory neurones but not to any loss of responsiveness of NK1 receptors. We also conclude that SP and NK1 receptors are involved predominantly in the development of capsaicin-induced mouse ear oedema.

Key words

Mouse ear oedema Capsaicin Tachyphylaxis Substance P NK1 receptor antagonist 

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Copyright information

© Birkhäuser Verlag, Basel 1995

Authors and Affiliations

  • H. Inoue
    • 1
  • N. Nagata
    • 1
  • Y. Koshihara
    • 2
  1. 1.Research LaboratoryMinophagen Pharmaceutical Co.ZamaJapan
  2. 2.Department of Biosignal ResearchTokyo Metropolitan Institute of GerontologyTokyoJapan

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