The Effect of Intrathecal Gabapentin on Neuropathetic Pain Model and the Role of NMDA Receptor

椎管內gabapentin對大白鼠神經痛的影響與NMDA受體的關係

葉靖宜(Chin-Yi Yeh) ； 林真福(Chen-Fuh Lam) ； 劉彥青(Yen-Chin Liu) ； 蔡玉娟(Yu-Chuan Tsai)

《中南盟研究年刊》 4卷1期 (2011/09) Pp. 1-8

https://doi.org/10.6850/JCSMA.201109_4(1).0001

摘要

目的：gabapentin被認為可降低神經痛，但其機轉未明。我們使用大白鼠坐骨神經痛模式來研究脊椎內給予gabapentin的機轉。在神經痛模式中，它曾被證實可經由抑制釋放glutamate而降低疼痛，我們的研究是在神經痛模式下對椎管內給予gabapentin合併有無給予NMDA受體的阻斷劑(MK 801)對疼痛的影響。方法：大白鼠隨機分配於控制或治療組（又分有無MK801組），PE-5的細管則放入腰椎脊柱內，3天後則綁坐骨神經以誘發神經痛，隔天則給予gabapentin連續14天，並以熱刺激評估後腳掌對藥物的反應。結果：注射gabapentin之大白鼠可延長對熱刺激的疼痛反應，但先給予MK 801似乎可更延長疼痛反應與von Frey測量。結論：脊椎內給予gabapentin治療神經痛也許與NMDA受體並不密切相關，脊椎內gabapentin的神經痛止痛機轉也許與全身的給予不同，真實機轉須近一步研究。可做進一步研究探討其詳細機制。

關鍵字

脊椎內注射 ； 神經痛 ； 治療後神經痛

並列摘要

Background. We used a model of neuropathic pain consisting of rats with chronic constriction injury (CCI) of the sciatic nerve to investigate the effect of gabapentin via intrathecal pathway. In neuropathetic pain model, it was thought to reduce pain by inhibiting glutamate release. In our study, we investigate the effect of intrathecal gabapentin on protein kinase Dγ subunit (PKCγ) in neuropathetic pain model.Methods. Male SD rats (250-380g) were randomly assigned to sham or gabapentin groups. PE-5 catheter was inserted to the lumbar enlargement of the spinal cord. CCI model was performed the day after the intrathecal surgery. Gabapentin was given after the day of CCI. Intrathecal administration of gabapentin (4.2 um) was performed by hand infusion slowly for 7 days. Pain-related behavior was assessed by measuring the latency of foot withdrawal elicited by noxious radiant heat applied to hindpaw plantar surface. The dosal horn of spine cord tissue on lumbar region was harvested at the end of experimental. The protein sample was analysis with Western blotting for PKCγ expression.Results. The duration change of pain-related behavior using radiant heat to hindpaw in CCI model was little changed with or without intrathecal gabapentin treatment. However, the expression PKCγ over lumbar spine area was significantly increased and suppressed by gabapentin treatment.Conclusion. Our results indicate that CCI induces PKCγ expression and the effect can be blunted by gabapentin treatment. We failed to demonstrated the antineuropathetic effect when intrathecal gabepentin administration. However, intrathecal gabepentin suppressed the protein expression in spinal cord. Further studies were needed for the detail mechanism.

並列關鍵字

Gabapentin ； intrathecal delivery ； Chronic constriction nerve injury ； protein kinase C gamma