Mechanical allodynia induced by paclitaxel, oxaliplatin and vincristine: different effectiveness of gabapentin and different expression of voltage-dependent calcium channel alpha(2)delta-1 subunit.
We compared the inhibitory action of gabapentin, which is used to treat neuropathic pain, on mechanical allodynia induced by chemotherapeutic agents, paclitaxel, oxaliplatin, and vincristine, in mice. Single injections of paclitaxel, oxaliplatin, and vincristine at the doses corresponding to doses clinically used caused mechanical allodynia of similar intensity. Oral administration of gabapentin (30, 100 mg/kg) produced a dose-dependent inhibition of allodynia caused by paclitaxel and oxaliplatin, but not vincristine. Intrathecal injection of gabapentin (30, 100microg/site) significantly inhibited allodynia induced by paclitaxel, but not oxaliplatin and vincristine. Intraplantar injection of gabapentin (30, 100 microg/site) did not significantly inhibit allodynia induced by paclitaxel and oxaliplatin. Paclitaxel increased the expression of mRNA of voltage-dependent calcium channel alpha(2)delta-1 subunit, an action site of gabapentin, in the dorsal spinal cord, and oxaliplatin increased it in the dorsal root ganglia. Vincristine was without effects on alpha(2)delta-1 subunit mRNA in these regions. These results suggest that the efficacy of gabapentin in the treatment of mechanical allodynia is dependent on chemotherapy agent used. It may be partly due to the distinct effects of chemotherapy agents on the expression of alpha(2)delta-1 subunit of voltage-dependent calcium channel.
Gauchan
Punam
P
Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.
Andoh
Tsugunobu
T
Ikeda
Kenichiro
K
Fujita
Masahide
M
Sasaki
Atsushi
A
Kato
Atsushi
A
Kuraishi
Yasushi
Y