Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
Korean Medicinal Herbs Research Team, National Development Institute of Korea Medicine, Jangheung, Republic of Korea.
Pharmacology. 2018;102(5-6):332-338. doi: 10.1159/000492394. Epub 2018 Oct 10.
This study examined the effects of intrathecal areca nut on spinal nerve-ligated and chemotherapy-induced neuropathic pain (NP), and investigated the relevance of spinal 5-hydroxytryptamine (5-HT) and α2-adrenergic receptors to those effects. For drug administration, intrathecal catheters were inserted into the subarachnoid space of male Sprague-Dawley rats. NP was induced either by spinal nerve ligation (left spinal nerves L5 and L6) or by chemotherapeutic injection (intraperitoneal cisplatin, 2 mg/kg/day, once daily for 4 days). Paw withdrawal thresholds (PWT) were mechanically assessed using von Frey filaments. The involvement of 5-HT and α2-adrenergic receptors in antiallodynia was determined using antagonists with the following receptor specificities: nonselective 5-HT (dihydroergocristine), 5-HT7 (SB269970), nonselective α2-adrenoceptor (yohimbine), α-2A (BRL 44408), α-2B (ARC 239), and α-2C (JP 1302). Intrathecal areca nut significantly increased the PWT in both spinal nerve-ligated and chemotherapy-induced NP (‡ p < 0.001). Intrathecal dihydroergocristine, SB269970, yohimbine, BRL 44408, ARC 239, and JP 1302 significantly reversed the antiallodynic effects of areca nut in both NP states (‡ p < 0.001). Collectively, intrathecal areca nut suppressed mechanical allodynia induced by spinal nerve ligation and cisplatin injection. Furthermore, spinal 5-HT7 receptor and α2A, α2B, and α2C-adrenoceptors contributed to the antiallodynic effects of areca nut.
本研究探讨了鞘内槟榔对脊神经结扎和化疗诱导的神经病理性疼痛（NP）的影响，并研究了脊髓 5-羟色胺（5-HT）和α2-肾上腺素能受体与这些效应的相关性。为了给药，将鞘内导管插入雄性 Sprague-Dawley 大鼠蛛网膜下腔。NP 是通过脊神经结扎（左侧脊神经 L5 和 L6）或化疗注射（腹腔注射顺铂，2mg/kg/天，每天一次，共 4 天）诱导的。使用 von Frey 细丝机械评估爪回缩阈值（PWT）。使用具有以下受体特异性的拮抗剂确定 5-HT 和 α2-肾上腺素能受体在抗痛觉过敏中的作用：非选择性 5-HT（二氢麦角隐亭）、5-HT7（SB269970）、非选择性 α2-肾上腺素能受体（育亨宾）、α-2A（BRL 44408）、α-2B（ARC 239）和 α-2C（JP 1302）。鞘内槟榔显著增加了脊神经结扎和化疗诱导的 NP 中的 PWT（‡p<0.001）。鞘内二氢麦角隐亭、SB269970、育亨宾、BRL 44408、ARC 239 和 JP 1302 显著逆转了槟榔在两种 NP 状态下的抗痛觉过敏作用（‡p<0.001）。总之，鞘内槟榔抑制了由脊神经结扎和顺铂注射引起的机械性痛觉过敏。此外，脊髓 5-HT7 受体和 α2A、α2B 和 α2C-肾上腺素能受体参与了槟榔的抗痛觉过敏作用。
