Novel expression of vanilloid receptor 1 on capsaicin-insensitive fibers accounts for the analgesic effect of capsaicin cream in neuropathic pain

Harunor Rashid, Makoto Inoue, Saori Kondo, Toshiko Kawashima, Shiho Bakoshi, Hiroshi Ueda

Research output: Contribution to journalArticlepeer-review

Abstract

Here, we investigated the mechanism of the antihyperalgesic effect of capsaicin cream in the nerve injury-induced neuropathic pain model in mice. In naive mice, application of capsaicin cream onto footpad caused no significant changes in the thermal latency in contrast to the severe thermal hyperalgesia induced by a capsaicin ointment. On the other hand, application of the cream 3 h before test concentration dependently reversed both thermal and mechanical hyperalgesia observed after partial sciatic nerve injury in mice. In algogenic-induced nociceptive flexion (ANF) test, application of 0.1% capsaicin cream in naive mice blocked intraplantar (i.pl.) nociceptin- and ATP-induced flexion responses, whereas prostaglandin I2 (PGI2) agonist-induced responses were unaffected. After nerve injury PGI2 agonist-induced flexion responses were hypersensitized, and capsaicin cream concentration dependently blocked these hyperalgesic responses. Intraplantar injection of capsaicin solution in ANF test also produced potent flexion responses in naive mice that were lost after neonatal capsaicintreatment. Partial sciatic nerve injury in neonatal capsaicintreated mice caused reappearance of i.pl. capsaicin-induced flexion responses, suggesting novel expression of capsaicin receptors due to injury. The PGI2 agonist-induced responses were also hypersensitized in such injured mice. Capsaicin cream completely reversed both i.pl. capsaicin- or i.pl. PGI2 agonist-induced hyperalgesia in neonatal capsaicin-treated injured mice. Finally, novel expression of VR1 receptors on neonatal capsaicin-insensitive neurons after nerve injury was confirmed by immunohistochemistry. The newly expressed VR1 receptors after nerve injury were mainly confined to A-fibers. Together, our results suggest that novel expression of capsaicin receptors in neuropathic condition contributes to the analgesic effects of the capsaicin cream.

Original languageEnglish (US)
Pages (from-to)940-948
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume304
Issue number3
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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