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Research ArticleNEUROPHARMACOLOGY

Novel Expression of Vanilloid Receptor 1 on Capsaicin-Insensitive Fibers Accounts for the Analgesic Effect of Capsaicin Cream in Neuropathic Pain

Md Harunor Rashid, Makoto Inoue, Saori Kondo, Toshiko Kawashima, Shiho Bakoshi and Hiroshi Ueda
Journal of Pharmacology and Experimental Therapeutics March 2003, 304 (3) 940-948; DOI: https://doi.org/10.1124/jpet.102.046250
Md Harunor Rashid
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Makoto Inoue
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Saori Kondo
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Toshiko Kawashima
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Shiho Bakoshi
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Hiroshi Ueda
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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 capsaicin-treatment. Partial sciatic nerve injury in neonatal capsaicin-treated mice caused reappearance of i.pl. capsaicin-induced flexion responses, suggesting novel expression of capsaicin receptors due to injury. The PGI2agonist-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.

Footnotes

  • Parts of this study were supported by Special Coordination Funds of the Science and Technology Agency of the Japanese Government, Research Grant from Environmental Agency, Government of Japan, grants-in-aid from the Ministry of Education, Science, Culture and Sports of Japan, and a grant for Human Frontier Science Program.

  • DOI: 10.1124/jpet.102.046250

  • Abbreviations:
    VR1
    vanilloid receptor 1
    SP
    substance P
    DRG
    dorsal root ganglion
    ANF
    algogenic-induced nociceptive flexion
    N/OFQ
    nociceptin/orphanin FQ
    PGI2
    prostaglandin I2
    i.pl.
    intraplantar
    PBS
    phosphate-buffered saline
    BK
    bradykinin
    ONO-54918-07
    15-cis-(4-N-propylcyclohexyl)-16,17,18,19,20-pentanor-9-deoxy-6,9α-nitriloprostaglandin F1
    • Received October 28, 2002.
    • Accepted November 25, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 304 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 304, Issue 3
1 Mar 2003
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Research ArticleNEUROPHARMACOLOGY

Novel Expression of Vanilloid Receptor 1 on Capsaicin-Insensitive Fibers Accounts for the Analgesic Effect of Capsaicin Cream in Neuropathic Pain

Md Harunor Rashid, Makoto Inoue, Saori Kondo, Toshiko Kawashima, Shiho Bakoshi and Hiroshi Ueda
Journal of Pharmacology and Experimental Therapeutics March 1, 2003, 304 (3) 940-948; DOI: https://doi.org/10.1124/jpet.102.046250

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Research ArticleNEUROPHARMACOLOGY

Novel Expression of Vanilloid Receptor 1 on Capsaicin-Insensitive Fibers Accounts for the Analgesic Effect of Capsaicin Cream in Neuropathic Pain

Md Harunor Rashid, Makoto Inoue, Saori Kondo, Toshiko Kawashima, Shiho Bakoshi and Hiroshi Ueda
Journal of Pharmacology and Experimental Therapeutics March 1, 2003, 304 (3) 940-948; DOI: https://doi.org/10.1124/jpet.102.046250
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