Gauchan Punam, Andoh Tsugunobu, Ikeda Kenichiro, Fujita Masahide, Sasaki Atsushi, Kato Atsushi, Kuraishi Yasushi
Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.
Biol Pharm Bull. 2009 Apr;32(4):732-4. doi: 10.1248/bpb.32.732.
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.
我们比较了用于治疗神经性疼痛的加巴喷丁对化疗药物紫杉醇、奥沙利铂和长春新碱在小鼠中诱导的机械性异常性疼痛的抑制作用。以临床使用剂量对应的剂量单次注射紫杉醇、奥沙利铂和长春新碱会引起强度相似的机械性异常性疼痛。口服加巴喷丁（30、100mg/kg）对紫杉醇和奥沙利铂引起的异常性疼痛产生剂量依赖性抑制，但对长春新碱无效。鞘内注射加巴喷丁（30、100μg/部位）可显著抑制紫杉醇诱导的异常性疼痛，但对奥沙利铂和长春新碱无效。足底注射加巴喷丁（30、100μg/部位）对紫杉醇和奥沙利铂诱导的异常性疼痛无显著抑制作用。紫杉醇增加了背根脊髓中电压依赖性钙通道α(2)δ-1亚基（加巴喷丁的作用位点）的mRNA表达，奥沙利铂增加了背根神经节中该亚基的表达。长春新碱对这些区域的α(2)δ-1亚基mRNA无影响。这些结果表明，加巴喷丁治疗机械性异常性疼痛的疗效取决于所使用的化疗药物。这可能部分归因于化疗药物对电压依赖性钙通道α(2)δ-1亚基表达的不同影响。
