Herbal medicine Shakuyaku-kanzo-to reduces paclitaxel-induced painful peripheral neuropathy in mice.
OBJECTIVE
Paclitaxel is widely used in cancer chemotherapy for the treatment of solid tumors such as breast, ovarian and lung cancer. However, it sometimes induces moderate to severe muscle pain, and impairs the patients' quality of life. An appropriate method for relieving this pain is not well established. Shakuyaku-kanzo-to, a herbal medicine, is known to relieve menstrual pain, muscle spasm, and muscle pain, and its effectiveness is expected. To ascertain the effectiveness of Shakuyaku-kanzo-to on paclitaxel-induced pain, we investigated the effects of Shakuyaku-kanzo-to and its constituent herbal medicines in a mouse model.


METHODS
Seven-week-old male ddY mice were used. To make a mouse model of paclitaxel-induced pain, different single, intraperitoneally injected doses of this drug were tested in various groups of mice, and the optimal dose was determined. To estimate the effects of Shakuyaku-kanzo-to, the constituent herbal medicines Shakuyaku and Kanzo, and loxoprofen sodium as a non-steroidal anti-inflammatory drug on paclitaxel-induced pain, mechanical allodynia and hyperalgesia of the hind paw were assessed.


RESULTS
Paclitaxel administered at a dose of 10mg/kg or more produced allodynia and hyperalgesia; the time courses were similar to those of pain after paclitaxel administration in cancer patients. Shakuyaku-kanzo-to significantly relieved the allodynia and hyperalgesia induced by paclitaxel (10mg/kg). Shakuyaku and Kanzo inhibited the allodynia and hyperalgesia to some extent, but not significantly, while loxoprofen sodium was without effects.


CONCLUSIONS
A single administration of paclitaxel (10mg/kg) produced allodynia and hyperalgesia in mice, suggesting that it could be used as an animal model resembling the painful conditions observed in humans medicated with this drug. Using this model, Shakuyaku-kanzo-to was shown to relieve paclitaxel-induced painful peripheral neuropathy.
Hidaka
Takao
T
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Toyama, 2630, Sugitani, Toyama-shi, Toyama 930-0194, Japan. hidaka@med.u-toyama.ac.jp
Shima
Tomoko
T
Nagira
Kiyofumi
K
Ieki
Masahiro
M
Nakamura
Takafumi
T
Aono
Yukiko
Y
Kuraishi
Yasushi
Y
Arai
Takashi
T
Saito
Shigeru
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D006035:Glycyrrhiza; D006930:Hyperalgesia / Q000175:diagnosis / Q000523:psychology; D008297:Male; D051379:Mice; D017239:Paclitaxel / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D029596:Paeonia; D010146:Pain / Q000139:chemically induced* / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D010666:Phenylpropionates / Q000627:therapeutic use; D010812:Physical Stimulation
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000972:Antineoplastic Agents, Phytogenic; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D010666:Phenylpropionates; C038462:shakuyaku-kanzoh-toh; C040656:loxoprofen; D017239:Paclitaxel