Koh Won Uk, Shin Jin Woo, Bang Ji-Yeon, Kim Sae Gyeol, Song Jun-Gol
From the Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Anesth Analg. 2016 Sep;123(3):762-70. doi: 10.1213/ANE.0000000000001411.
Nefopam hydrochloride is a centrally acting compound that induces antinociceptive and antihyperalgesic properties in neuropathic pain models. Previous reports have shown that activation of adenosine triphosphate (ATP)-sensitive and calcium-activated potassium (KATP and KCa2+) channels has antiallodynic effects in neuropathic pain. In the present study, we evaluated the relationship between potassium channels and nefopam to determine whether the antiallodynic effects of nefopam are mediated by potassium channels in a neuropathic pain model.
Mechanical allodynia was induced by spinal nerve ligation (SNL) in rats, and the paw withdrawal threshold (PWT) was evaluated by the use of von Frey filaments. Nefopam was administered intraperitoneally before or after SNL. We assessed the relationship between nefopam and intrathecal injection of the KCa2+ channel antagonists apamin and charybdotoxin, and the KATP channel blocker glibenclamide to assess their abilities to reverse the antiallodynic effects of nefopam. In addition, we evaluated whether the KATP channel opener pinacidil had antiallodynic effects and promoted the antiallodynic effects of nefopam.
Administration of nefopam before and after SNL induced significant antiallodynic effects (P < .01, respectively), which were significantly reduced by glibenclamide (P < .01). Pinacidil improved the antiallodynic effects of nefopam (P < .01); however, apamin and charybdotoxin had little effects on the antiallodynic properties of nefopam.
The antiallodynic effects of nefopam are increased by a KATP channel agonist and reversed by a KATP channel antagonist. These data suggest that the KATP channel is involved in the antiallodynic effects of nefopam in a neuropathic pain model.
盐酸奈福泮是一种中枢作用化合物，在神经病理性疼痛模型中具有诱导抗伤害感受和抗痛觉过敏的特性。先前的报告表明，三磷酸腺苷（ATP）敏感性和钙激活钾（KATP和KCa2+）通道的激活在神经病理性疼痛中具有抗痛觉过敏作用。在本研究中，我们评估了钾通道与奈福泮之间的关系，以确定奈福泮的抗痛觉过敏作用是否由神经病理性疼痛模型中的钾通道介导。
通过结扎大鼠脊神经（SNL）诱导机械性异常性疼痛，并使用von Frey细丝评估爪部缩足阈值（PWT）。在SNL之前或之后腹腔注射奈福泮。我们评估了奈福泮与鞘内注射KCa2+通道拮抗剂蜂毒明肽和大蝎毒素以及KATP通道阻滞剂格列本脲之间的关系，以评估它们逆转奈福泮抗痛觉过敏作用的能力。此外，我们评估了KATP通道开放剂吡那地尔是否具有抗痛觉过敏作用并增强奈福泮的抗痛觉过敏作用。
SNL前后给予奈福泮均诱导出显著的抗痛觉过敏作用（分别为P <.01），格列本脲使其显著降低（P <.01）。吡那地尔增强了奈福泮的抗痛觉过敏作用（P <.01）；然而，蜂毒明肽和大蝎毒素对奈福泮的抗痛觉过敏特性几乎没有影响。
KATP通道激动剂可增强奈福泮的抗痛觉过敏作用，而KATP通道拮抗剂可逆转该作用。这些数据表明，KATP通道参与了奈福泮在神经病理性疼痛模型中的抗痛觉过敏作用。
