TY - JOUR
T1 - Novel expression of vanilloid receptor 1 on capsaicin-insensitive fibers accounts for the analgesic effect of capsaicin cream in neuropathic pain
AU - Rashid, Harunor
AU - Inoue, Makoto
AU - Kondo, Saori
AU - Kawashima, Toshiko
AU - Bakoshi, Shiho
AU - Ueda, Hiroshi
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/3/1
Y1 - 2003/3/1
N2 - 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.
AB - 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.
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U2 - 10.1124/jpet.102.046250
DO - 10.1124/jpet.102.046250
M3 - Article
C2 - 12604668
AN - SCOPUS:0037373066
SN - 0022-3565
VL - 304
SP - 940
EP - 948
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 3
ER -