Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Belo Horizonte, MG, CEP 31270-901, Brazil.
Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Belo Horizonte, MG, CEP 31270-901, Brazil.
Pharmacol Rep. 2024 Oct;76(5):1067-1078. doi: 10.1007/s43440-024-00640-2. Epub 2024 Aug 23.
Recently, we demonstrated that nicorandil inhibits mechanical allodynia induced by paclitaxel. In the present study, we evaluated the effect induced by nicorandil in a model of neuropathic pain induced by chronic constriction injury (CCI) in mice. We also investigated putative mechanisms underlying such an effect.
CCI was induced by three ligatures of the left sciatic nerve. Mechanical allodynia was evaluated by measuring the paw withdrawal threshold with an electronic von Frey apparatus. Concentrations of cytokines and myeloperoxidase activity were determined in the paw tissue, sciatic nerve, and dorsal root ganglia (DRG).
Oral administration of two doses of nicorandil (150 mg/kg po), but not equimolar doses of nicotinamide or nicotinic acid, attenuated mechanical allodynia induced by CCI. Nicorandil activity was reduced by previous administration of glibenclamide (40 mg/kg) or naltrexone (5 mg/kg or 10 mg/kg). Two doses of nicorandil (150 mg/kg, po) reduced tumor necrosis factor-α, interleukin-1β and interleukin-6, but not CXCL-1, concentrations in the paw tissue of CCI mice. Two doses of nicorandil (150 mg/kg, po) reduced concentrations of all these mediators in the sciatic nerve and DRG. Two doses of nicorandil (150 mg/kg, po) also reduced the myeloperoxidase activity in the paw tissue, sciatic nerve, and DRG.
Nicorandil exhibits antiallodynic activity in a model of neuropathic pain induced by CCI. Inhibition of cytokines production and reduction of neutrophils recruitment in paw tissue, sciatic nerve, and DRG as well as activation of ATP-dependent potassium channels and opioidergic pathways, underlie nicorandil antiallodynic activity.
最近，我们证明了尼可地尔抑制紫杉醇引起的机械性痛觉过敏。在本研究中，我们评估了尼可地尔在慢性缩窄性损伤（CCI）诱导的小鼠神经性疼痛模型中的作用。我们还研究了这种作用的潜在机制。
通过三个左坐骨神经结扎来诱导 CCI。通过电子 von Frey 仪器测量足底退缩阈值来评估机械性痛觉过敏。在足底组织、坐骨神经和背根神经节（DRG）中测定细胞因子和髓过氧化物酶活性的浓度。
尼可地尔（150mg/kg 口服）的两个剂量，但不是烟酰胺或烟酸的等摩尔剂量，可减轻 CCI 引起的机械性痛觉过敏。尼可地尔的活性被格列本脲（40mg/kg）或纳曲酮（5mg/kg 或 10mg/kg）预先给药所减弱。尼可地尔（150mg/kg，口服）的两个剂量降低了 CCI 小鼠足底组织中肿瘤坏死因子-α、白细胞介素-1β 和白细胞介素-6 的浓度，但不降低 CXCL-1 的浓度。尼可地尔（150mg/kg，口服）的两个剂量还降低了坐骨神经和 DRG 中所有这些介质的浓度。尼可地尔（150mg/kg，口服）的两个剂量也降低了足底组织、坐骨神经和 DRG 中的髓过氧化物酶活性。
尼可地尔在 CCI 诱导的神经性疼痛模型中表现出抗痛觉过敏活性。细胞因子产生的抑制和在足底组织、坐骨神经和 DRG 中中性粒细胞募集的减少，以及 ATP 依赖性钾通道和阿片能途径的激活，是尼可地尔抗痛觉过敏活性的基础。
