Effects of vitamin D administration on nociception and spinal cord pro-oxidant and antioxidant markers in a rat model of neuropathic pain

Reactive oxygen species (ROS) are involved in neuropathic pain, a complicated condition after nerve tissue lesion. Vitamin D appears to improve symptoms of pain and exhibits antioxidant properties. We investigated the effects of oral administration of vitamin D3, the active form of vitamin D, on nociception, the sciatic functional index (SFI), and spinal cord pro-oxidant and antioxidant markers in rats with chronic constriction injury (CCI) of the sciatic nerve, a model of neuropathic pain. Vitamin D3 (500 IU/kg per day) attenuated the CCI-induced decrease in mechanical withdrawal threshold and thermal withdrawal latency (indicators of antinociception) and SFI. The vitamin prevented increased lipid hydroperoxide levels in injured sciatic nerve without change to total antioxidant capacity (TAC). Vitamin D3 prevented increased lipid hydroperoxide, superoxide anion generation (SAG), and hydrogen peroxide (H2O2) levels in the spinal cord, which were found in rats without treatment at 7 and 28 days post-CCI. A significant negative correlation was found between mechanical threshold and SAG and between mechanical threshold and H2O2 at day 7. Vitamin D3 also prevented decreased spinal cord total thiols content. There was an increase in TAC in the spinal cord of vitamin-treated CCI rats, compared to CCI rats without treatment only at 28 days. No significant changes were found in body weight and blood parameters of hepatic and renal function. These findings demonstrated, for first time, that vitamin D modulated pro-oxidant and antioxidant markers in the spinal cord. Since antinociception occurred in parallel with oxidative changes in the spinal cord, the oxidative changes may have contributed to vitamin D-induced antinociception.

活性氧簇（Reactive oxygen species, ROS）参与神经病理性疼痛的发生发展，该病症是神经组织损伤后引发的一类复杂疾病状态。维生素D可改善疼痛症状，同时具备抗氧化特性。本研究探讨了口服活性形式维生素D3对慢性压迫性损伤（chronic constriction injury, CCI）模型大鼠痛觉感受、坐骨神经功能指数（sciatic functional index, SFI）以及脊髓促氧化与抗氧化标志物的影响，其中CCI是经典的神经病理性疼痛动物模型。实验中，大鼠每日以500 IU/kg的剂量口服维生素D3，结果显示其可缓解CCI诱导的机械撤足阈值与热撤足潜伏期（抗伤害感受的核心检测指标）及SFI的下降。维生素D可抑制受损坐骨神经内脂质过氧化物水平升高，且未改变总抗氧化能力（total antioxidant capacity, TAC）。在CCI造模后第7天和第28天，未接受治疗的大鼠脊髓内脂质过氧化物、超氧阴离子生成（superoxide anion generation, SAG）及过氧化氢（hydrogen peroxide, H₂O₂）水平均显著升高，而维生素D3可阻断上述变化。造模第7天时，机械撤足阈值与SAG、H₂O₂水平分别呈显著负相关。此外，维生素D3可阻止脊髓总巯基含量降低。与未接受治疗的CCI大鼠相比，仅在造模后第28天，经维生素D处理的CCI大鼠脊髓内TAC水平才出现显著升高。两组大鼠的体重及肝肾功能相关血液指标均未出现显著变化。本研究首次证实，维生素D可调控脊髓内的促氧化与抗氧化标志物。由于抗伤害感受效应与脊髓内的氧化应激变化同步发生，提示氧化应激变化可能参与了维生素D诱导的抗伤害感受作用。