Maneuf Y P, Blake R, Andrews N A, McKnight A T
Cambridge Biotechnology Ltd, PO Box 230, Cambridge CB2 1XJ.
Br J Pharmacol. 2004 Feb;141(4):574-9. doi: 10.1038/sj.bjp.0705579. Epub 2004 Jan 26.
Recently, we showed that gabapentin can inhibit a facilitatory effect of substance P (SP) on K(+)-evoked glutamate release in rat trigeminal slices (Maneuf et al., 2001), and we have now examined the effect of gabapentin on glutamate release in the trigeminal slice from the streptozotocin (STZ)-treated rat. 1. At 4 weeks following STZ treatment (50 mg kg(-1) i.p.), blood glucose was increased in the majority of cases, compared to the control level. All the treated animals showed a significant degree (P<0.001) of tactile allodynia (assessed using von Frey filaments) that did not appear to correlate with blood glucose levels. 2. In this study, we demonstrated that, after STZ treatment, 30 microM gabapentin reduced K(+)-evoked release of [(3)H]-glutamate in either normal (11 mM) or high (30 mM) glucose conditions by 24 and 22%, respectively. In the normal rat, gabapentin (up to 100 microM) is ordinarily unable to affect release of glutamate from the trigeminal slice. 3. The uptake of glutamate in Sp5C punches from streptozotocin-treated rats was reduced under normal glucose conditions (41.7% of control), whereas high glucose restored uptake to normal (84.7% of control). 4. The addition of 1 microm substance P potentiated the evoked release of glutamate in both normal (40% increase) and high glucose (28%), and this was blocked by gabapentin (30 microM) in both conditions. It is interesting to speculate that this ability of gabapentin to reduce the release of glutamate in the trigeminal nucleus after streptozotocin treatment may be of relevance to the antihyperalgesic-allodynic actions of the drug.
最近，我们发现加巴喷丁能够抑制P物质（SP）对大鼠三叉神经切片中钾离子诱发的谷氨酸释放的促进作用（马纽夫等人，2001年），并且我们现在研究了加巴喷丁对链脲佐菌素（STZ）处理的大鼠三叉神经切片中谷氨酸释放的影响。1. 在STZ处理（腹腔注射50 mg kg⁻¹）4周后，与对照水平相比，大多数情况下血糖升高。所有处理的动物均表现出显著程度（P<0.001）的触觉异常性疼痛（使用von Frey细丝评估），这似乎与血糖水平无关。2. 在本研究中，我们证明，STZ处理后，30 μM加巴喷丁在正常（11 mM）或高（30 mM）葡萄糖条件下分别使钾离子诱发的[³H] - 谷氨酸释放减少24%和22%。在正常大鼠中，加巴喷丁（高达100 μM）通常无法影响三叉神经切片中谷氨酸的释放。3. 在正常葡萄糖条件下，链脲佐菌素处理的大鼠Sp5C穿孔中谷氨酸的摄取减少（为对照的41.7%），而高葡萄糖使摄取恢复正常（为对照的84.7%）。4. 添加1 μM P物质可增强正常（增加40%）和高葡萄糖（增加28%）条件下谷氨酸的诱发释放，并且在两种条件下均被加巴喷丁（30 μM）阻断。有趣的是，可以推测加巴喷丁在链脲佐菌素处理后减少三叉神经核中谷氨酸释放的这种能力可能与该药物的抗痛觉过敏 - 异常性疼痛作用有关。
