Department of Anesthesiology and Pain Medicine, University of Ulsan College of Medicine, Asan Medical Center, Songpa-gu, Seoul, 138-736, Korea.
Anesth Analg. 2011 Jun;112(6):1494-9. doi: 10.1213/ANE.0b013e318212b833. Epub 2011 May 5.
Nerve injury can generate neuropathic pain. The accompanying mechanical allodynia may be reduced by the intrathecal administration of adenosine. The neuroprotective effects of adenosine are mediated by the adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channel. We assessed the relationship between the adenosine A1 receptor agonist, N⁶-(R)-phenylisopropyl adenosine (R-PIA), and K(ATP) channels to determine whether the antiallodynic effects of R-PIA are also mediated through K(ATP) channels in a rat nerve ligation injury model of neuropathic pain.
Mechanical allodynia was induced by tight ligation of the left lumbar fifth and sixth spinal nerves. Mechanical allodynia in the left hindpaw was evaluated using von Frey filaments to measure withdrawal thresholds. R-PIA (0.5, 1, or 2 μg) was administered intrathecally to induce antiallodynia. We assessed whether pretreatment with the K(ATP) channel blockers glibenclamide or 5-hydroxydecanoate reversed the antiallodynic effect of R-PIA. Also, we evaluated whether diazoxide, a K(ATP) channel opener, had an antiallodynic effect and promoted the antiallodynic effect of R-PIA. Lastly, we investigated whether the voltage-activated K channel blocker 4-aminopyridine attenuated the effect of R-PIA.
Intrathecal R-PIA produced maximal antiallodynia at 2 μg (P < 0.05). Intrathecal pretreatment with glibenclamide and intraperitoneal pretreatment 5-hydroxydecanoate significantly reduced the antiallodynic effect of R-PIA. Diazoxide produced an antiallodynic effect and also enhanced the antiallodynic action of R-PIA. 4-Aminopyridine had no effect on the antiallodynic action of R-PIA.
The antiallodynic effects of adenosine A1 receptor stimulation may be related to K(ATP) channel activity in a rat model of nerve ligation injury.
神经损伤可引发神经性疼痛。鞘内给予腺苷可减轻伴随的机械性痛觉过敏。腺苷的神经保护作用是由三磷酸腺苷（ATP）敏感钾（KATP）通道介导的。我们评估了腺苷 A1 受体激动剂 N⁶-（R）-苯异丙基腺苷（R-PIA）与 KATP 通道之间的关系，以确定在大鼠神经结扎损伤模型中，R-PIA 的抗痛觉过敏作用是否也通过 KATP 通道介导。
通过紧结扎左侧腰 5 和 6 脊神经来诱导机械性痛觉过敏。使用 von Frey 细丝测量左后爪的撤回阈值来评估左后爪的机械性痛觉过敏。鞘内给予 R-PIA（0.5、1 或 2μg）以诱导抗痛觉过敏。我们评估了 KATP 通道阻滞剂格列本脲或 5-羟癸酸是否逆转了 R-PIA 的抗痛觉过敏作用。此外，我们评估了 KATP 通道开放剂二氮嗪是否具有抗痛觉过敏作用，并促进了 R-PIA 的抗痛觉过敏作用。最后，我们研究了电压激活的 K 通道阻滞剂 4-氨基吡啶是否减弱了 R-PIA 的作用。
鞘内给予 R-PIA 产生最大的抗痛觉过敏作用，剂量为 2μg（P<0.05）。鞘内给予格列本脲预处理和腹腔内给予 5-羟癸酸预处理显著降低了 R-PIA 的抗痛觉过敏作用。二氮嗪产生抗痛觉过敏作用，并增强了 R-PIA 的抗痛觉过敏作用。4-氨基吡啶对 R-PIA 的抗痛觉过敏作用没有影响。
在大鼠神经结扎损伤模型中，腺苷 A1 受体刺激的抗痛觉过敏作用可能与 KATP 通道活性有关。
