Involvement of substance P in peripheral neuropathy induced by paclitaxel but not oxaliplatin

Yoko Tatsushima, Nobuaki Egashira, Takehiro Kawashiri, Yuki Mihara, Takahisa Yano, Kazuto Mishima, Ryozo Oishi

研究成果: ジャーナルへの寄稿記事

33 引用 (Scopus)

抄録

The painful peripheral neuropathy occurring frequently during chemotherapy with paclitaxel or oxaliplatin is one of their dose-limiting factors. We reported previously that substance P is involved in the pathogenesis of pulmonary hypersensitivity reaction to paclitaxel in rats, and an antiallergic agent pemirolast reverses this reaction via the blockade of release of substance P. In the present study, we investigated the involvement of substance P in paclitaxel-induced peripheral neuropathy compared with that by oxaliplatin. In von Frey and acetone tests in rats repeated administration of paclitaxel (6 mg/kg i.p., once a week for 4 weeks) or oxaliplatin (4 mg/kg i.p., twice a week for 4 weeks) induced both mechanical allodynia and cold hyperalgesia. Paclitaxel-induced peripheral neuropathy was reversed primarily by the acute administration of pemirolast (0.1 and 1 mg/kg p.o.). Moreover, coadministration of the receptor antagonists neurokinin 1 [N-acetyl-L-tryptophan 3,5-bis(trifluoromethyl)benzylester (L-732,138), 100 μg/body i.t.] and neurokinin 2 [5-fluoro-3-[2-[4-methoxy-4-[[(R)-phenylsulphinyl]-methyl]-1- piperidinyl]ethyl]-1H-indole (GR159897), 100 μg/body i.t.] strongly reversed paclitaxel-induced neuropathy. On the other hand, oxaliplatin-induced peripheral neuropathy was not reversed by pemirolast. In the in vitro study using cultured adult rat dorsal root ganglion neurons paclitaxel (1000 ng/ml) significantly increased the release of substance P, and pemirolast (100 and 1000 nM) significantly inhibited this increase of substance P release. Oxaliplatin, by contrast, did not increase the release of substance P. These results suggest that substance P is involved in paclitaxel-induced neuropathy, and the mechanism of its action is clearly different from that of oxaliplatin.

元の言語英語
ページ(範囲)226-235
ページ数10
ジャーナルJournal of Pharmacology and Experimental Therapeutics
337
発行部数1
DOI
出版物ステータス出版済み - 4 1 2011

Fingerprint

oxaliplatin
pemirolast
Peripheral Nervous System Diseases
Substance P
Paclitaxel
Hyperalgesia
3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan
Neurokinin-1 Receptor Antagonists
Anti-Allergic Agents
Spinal Ganglia
Acetone

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

これを引用

Involvement of substance P in peripheral neuropathy induced by paclitaxel but not oxaliplatin. / Tatsushima, Yoko; Egashira, Nobuaki; Kawashiri, Takehiro; Mihara, Yuki; Yano, Takahisa; Mishima, Kazuto; Oishi, Ryozo.

:: Journal of Pharmacology and Experimental Therapeutics, 巻 337, 番号 1, 01.04.2011, p. 226-235.

研究成果: ジャーナルへの寄稿記事

Tatsushima, Yoko ; Egashira, Nobuaki ; Kawashiri, Takehiro ; Mihara, Yuki ; Yano, Takahisa ; Mishima, Kazuto ; Oishi, Ryozo. / Involvement of substance P in peripheral neuropathy induced by paclitaxel but not oxaliplatin. :: Journal of Pharmacology and Experimental Therapeutics. 2011 ; 巻 337, 番号 1. pp. 226-235.
@article{a16b61378cc24f559dbb57cadb1edab0,
title = "Involvement of substance P in peripheral neuropathy induced by paclitaxel but not oxaliplatin",
abstract = "The painful peripheral neuropathy occurring frequently during chemotherapy with paclitaxel or oxaliplatin is one of their dose-limiting factors. We reported previously that substance P is involved in the pathogenesis of pulmonary hypersensitivity reaction to paclitaxel in rats, and an antiallergic agent pemirolast reverses this reaction via the blockade of release of substance P. In the present study, we investigated the involvement of substance P in paclitaxel-induced peripheral neuropathy compared with that by oxaliplatin. In von Frey and acetone tests in rats repeated administration of paclitaxel (6 mg/kg i.p., once a week for 4 weeks) or oxaliplatin (4 mg/kg i.p., twice a week for 4 weeks) induced both mechanical allodynia and cold hyperalgesia. Paclitaxel-induced peripheral neuropathy was reversed primarily by the acute administration of pemirolast (0.1 and 1 mg/kg p.o.). Moreover, coadministration of the receptor antagonists neurokinin 1 [N-acetyl-L-tryptophan 3,5-bis(trifluoromethyl)benzylester (L-732,138), 100 μg/body i.t.] and neurokinin 2 [5-fluoro-3-[2-[4-methoxy-4-[[(R)-phenylsulphinyl]-methyl]-1- piperidinyl]ethyl]-1H-indole (GR159897), 100 μg/body i.t.] strongly reversed paclitaxel-induced neuropathy. On the other hand, oxaliplatin-induced peripheral neuropathy was not reversed by pemirolast. In the in vitro study using cultured adult rat dorsal root ganglion neurons paclitaxel (1000 ng/ml) significantly increased the release of substance P, and pemirolast (100 and 1000 nM) significantly inhibited this increase of substance P release. Oxaliplatin, by contrast, did not increase the release of substance P. These results suggest that substance P is involved in paclitaxel-induced neuropathy, and the mechanism of its action is clearly different from that of oxaliplatin.",
author = "Yoko Tatsushima and Nobuaki Egashira and Takehiro Kawashiri and Yuki Mihara and Takahisa Yano and Kazuto Mishima and Ryozo Oishi",
year = "2011",
month = "4",
day = "1",
doi = "10.1124/jpet.110.175976",
language = "English",
volume = "337",
pages = "226--235",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "1",

}

TY - JOUR

T1 - Involvement of substance P in peripheral neuropathy induced by paclitaxel but not oxaliplatin

AU - Tatsushima, Yoko

AU - Egashira, Nobuaki

AU - Kawashiri, Takehiro

AU - Mihara, Yuki

AU - Yano, Takahisa

AU - Mishima, Kazuto

AU - Oishi, Ryozo

PY - 2011/4/1

Y1 - 2011/4/1

N2 - The painful peripheral neuropathy occurring frequently during chemotherapy with paclitaxel or oxaliplatin is one of their dose-limiting factors. We reported previously that substance P is involved in the pathogenesis of pulmonary hypersensitivity reaction to paclitaxel in rats, and an antiallergic agent pemirolast reverses this reaction via the blockade of release of substance P. In the present study, we investigated the involvement of substance P in paclitaxel-induced peripheral neuropathy compared with that by oxaliplatin. In von Frey and acetone tests in rats repeated administration of paclitaxel (6 mg/kg i.p., once a week for 4 weeks) or oxaliplatin (4 mg/kg i.p., twice a week for 4 weeks) induced both mechanical allodynia and cold hyperalgesia. Paclitaxel-induced peripheral neuropathy was reversed primarily by the acute administration of pemirolast (0.1 and 1 mg/kg p.o.). Moreover, coadministration of the receptor antagonists neurokinin 1 [N-acetyl-L-tryptophan 3,5-bis(trifluoromethyl)benzylester (L-732,138), 100 μg/body i.t.] and neurokinin 2 [5-fluoro-3-[2-[4-methoxy-4-[[(R)-phenylsulphinyl]-methyl]-1- piperidinyl]ethyl]-1H-indole (GR159897), 100 μg/body i.t.] strongly reversed paclitaxel-induced neuropathy. On the other hand, oxaliplatin-induced peripheral neuropathy was not reversed by pemirolast. In the in vitro study using cultured adult rat dorsal root ganglion neurons paclitaxel (1000 ng/ml) significantly increased the release of substance P, and pemirolast (100 and 1000 nM) significantly inhibited this increase of substance P release. Oxaliplatin, by contrast, did not increase the release of substance P. These results suggest that substance P is involved in paclitaxel-induced neuropathy, and the mechanism of its action is clearly different from that of oxaliplatin.

AB - The painful peripheral neuropathy occurring frequently during chemotherapy with paclitaxel or oxaliplatin is one of their dose-limiting factors. We reported previously that substance P is involved in the pathogenesis of pulmonary hypersensitivity reaction to paclitaxel in rats, and an antiallergic agent pemirolast reverses this reaction via the blockade of release of substance P. In the present study, we investigated the involvement of substance P in paclitaxel-induced peripheral neuropathy compared with that by oxaliplatin. In von Frey and acetone tests in rats repeated administration of paclitaxel (6 mg/kg i.p., once a week for 4 weeks) or oxaliplatin (4 mg/kg i.p., twice a week for 4 weeks) induced both mechanical allodynia and cold hyperalgesia. Paclitaxel-induced peripheral neuropathy was reversed primarily by the acute administration of pemirolast (0.1 and 1 mg/kg p.o.). Moreover, coadministration of the receptor antagonists neurokinin 1 [N-acetyl-L-tryptophan 3,5-bis(trifluoromethyl)benzylester (L-732,138), 100 μg/body i.t.] and neurokinin 2 [5-fluoro-3-[2-[4-methoxy-4-[[(R)-phenylsulphinyl]-methyl]-1- piperidinyl]ethyl]-1H-indole (GR159897), 100 μg/body i.t.] strongly reversed paclitaxel-induced neuropathy. On the other hand, oxaliplatin-induced peripheral neuropathy was not reversed by pemirolast. In the in vitro study using cultured adult rat dorsal root ganglion neurons paclitaxel (1000 ng/ml) significantly increased the release of substance P, and pemirolast (100 and 1000 nM) significantly inhibited this increase of substance P release. Oxaliplatin, by contrast, did not increase the release of substance P. These results suggest that substance P is involved in paclitaxel-induced neuropathy, and the mechanism of its action is clearly different from that of oxaliplatin.

UR - http://www.scopus.com/inward/record.url?scp=79953004597&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953004597&partnerID=8YFLogxK

U2 - 10.1124/jpet.110.175976

DO - 10.1124/jpet.110.175976

M3 - Article

C2 - 21233199

AN - SCOPUS:79953004597

VL - 337

SP - 226

EP - 235

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 1

ER -