鞘内和全身给予加巴喷丁对脊髓 P 物质释放的影响。
The effects of intrathecal and systemic gabapentin on spinal substance P release.
机构信息
Department of Anesthesiology, Dokkyo Medical University, School of Medicine, Tochigi, Japan.
出版信息
Anesth Analg. 2011 Apr;112(4):971-6. doi: 10.1213/ANE.0b013e31820f2a16. Epub 2011 Mar 8.
BACKGROUND
Gabapentin binds at the extracellular α2δ1 subunit of voltage- sensitive calcium channels. Some voltage-sensitive calcium channels regulate substance P release from small primary afferents. We sought to determine in vivo whether spinal and systemic gabapentin at antihyperalgesic doses will attenuate substance P release.
METHODS
Rats prepared with chronic intrathecal (IT) catheters received IT vehicle or gabapentin 10 minutes before intraplantar formalin (5%, 50 μL) injection. For systemic studies, vehicle or gabapentin was delivered intraperitoneally (IP) 15 minutes before formalin injection. In separate groups of rats, to assess the effect of IT or IP gabapentin upon formalin-evoked substance P release, animals received similar treatment for assessment of flinching, but underwent transcardial perfusion with 4% paraformaldehyde 10 minutes after the formalin injection. Substance P release was determined by the incidence of neurokinin 1 receptor (NK1r) internalization in the ipsilateral and contralateral superficial dorsal horn in immunofluorescent stained tissues.
RESULTS
Unilateral intraplantar formalin evoked biphasic hindpaw flinching. IT gabapentin (100 and 200 μg) and IP gabapentin (100 and 200 mg/kg) resulted in a dose-dependent reduction in phase 2, but not phase 1, flinching in comparison with vehicle-treated rats. Intraplanatar formalin resulted in NK1r internalization in the ipsilateral, but not contralateral, superficial dorsal horn. IT gabapentin (200 μg, but not 100 μg) and IP gabapentin (200 mg/kg, but not 100 mg/kg) significantly reduced ipsilateral NK1r internalization in comparison with vehicle-treated control. Importantly, internalization evoked by IT substance P was not blocked by IT gabapentin.
CONCLUSION
Systemic and spinal gabapentin have an acute inhibitory effect on the release of substance P from small primary afferents and a concurrent effect upon the initiation of facilitated pain states.
背景
加巴喷丁与电压敏感性钙通道的细胞外α2δ1 亚基结合。一些电压敏感性钙通道调节从小的初级传入纤维释放 P 物质。我们试图确定体内抗痛觉过敏剂量的脊髓和全身加巴喷丁是否会减弱 P 物质的释放。
方法
用慢性鞘内（IT）导管制备的大鼠在足底内注射福尔马林（5%，50 μL）前 10 分钟接受 IT 载体或加巴喷丁。对于系统研究，在福尔马林注射前 15 分钟给予载体或加巴喷丁腹膜内（IP）。在单独的大鼠组中，为了评估 IT 或 IP 加巴喷丁对福尔马林诱发的 P 物质释放的影响，动物接受类似的治疗以评估退缩，但在福尔马林注射后 10 分钟用 4%多聚甲醛进行心脏灌注。通过免疫荧光染色组织中同侧和对侧浅层背角中神经激肽 1 受体（NK1r）内化的发生率来确定 P 物质的释放。
结果
单侧足底内福尔马林诱发双相后爪退缩。与载体处理的大鼠相比，IT 加巴喷丁（100 和 200 μg）和 IP 加巴喷丁（100 和 200 mg/kg）导致相 2，但不包括相 1，退缩呈剂量依赖性减少。足底内福尔马林导致同侧浅层背角中 NK1r 内化，但对侧没有。与载体处理的对照相比，IT 加巴喷丁（200 μg，但不是 100 μg）和 IP 加巴喷丁（200 mg/kg，但不是 100 mg/kg）显著减少同侧 NK1r 内化。重要的是，IT P 物质引起的内化不能被 IT 加巴喷丁阻断。
结论
全身和脊髓加巴喷丁对从小的初级传入纤维释放 P 物质具有急性抑制作用，并对促进疼痛状态的启动具有并发作用。
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