曲马多给药对大鼠髋关节骨关节炎模型的镇痛作用及关节炎变化。
Analgesic effects and arthritic changes following tramadol administration in a rat hip osteoarthritis model.
机构信息
Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba City, Japan.
Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba City, Japan.
出版信息
J Orthop Res. 2022 Aug;40(8):1770-1777. doi: 10.1002/jor.25208. Epub 2021 Nov 15.
We investigated the analgesic effects of tramadol and the arthritic changes following tramadol administration in the rat hip osteoarthritis (OA) model using mono-iodoacetate (MIA). The right hip joints of male Sprague-Dawley rats (n = 5 rats/group) in the Sham group were injected with 25 μl of sterile saline and 1% of fluorogold (FG) retrograde neurotracer. In the MIA + Vehicle and MIA + Tramadol groups, FG and 25 μl of sterile saline with 0.5 mg of MIA were injected into the right hip joint. The MIA + Vehicle and MIA + Tramadol groups were administered daily for 4 weeks, either sterile saline (10 mg/kg, intraperitoneal [i.p.]) or tramadol (10 mg/kg, i.p.). We assessed hyperalgesia every week after MIA administration. Histopathological changes and immunoreactive neurons for calcitonin gene-related peptide (CGRP) in dorsal root ganglia (DRG) were evaluated after 4 weeks of treatment. MIA injection into the hip joint led to mechanical hyperalgesia (p < 0.01), which was significantly reduced by tramadol administration (p < 0.01). Furthermore, daily i.p injection of tramadol significantly suppressed CGRP expression in DRG (p < 0.0001). MIA + Vehicle and MIA + Tramadol groups showed significant cartilage reduction and degeneration compared to the Sham group (p < 0.0001). Interestingly, OA changes significantly progressed in the MIA + Tramadol group compared to the MIA + Vehicle group (p < 0.0001).
我们使用单碘乙酸(MIA)研究了曲马多在大鼠髋骨骨关节炎(OA)模型中的镇痛作用和曲马多给药后的关节炎变化。在 Sham 组中,雄性 Sprague-Dawley 大鼠(每组 5 只)的右髋关节注射 25μl 无菌盐水和 1%荧光金(FG)逆行神经示踪剂。在 MIA+Vehicle 和 MIA+Tramadol 组中,FG 和 25μl 含 0.5mg MIA 的无菌盐水被注射到右髋关节。MIA+Vehicle 和 MIA+Tramadol 组每天接受 4 周治疗,分别给予无菌盐水(10mg/kg,腹腔内 [i.p.])或曲马多(10mg/kg,i.p.)。在 MIA 给药后每周评估痛觉过敏。在治疗 4 周后评估背根神经节(DRG)中降钙素基因相关肽(CGRP)的组织病理学变化和免疫反应性神经元。MIA 注射到髋关节导致机械性痛觉过敏(p<0.01),曲马多给药显著减轻了这种痛觉过敏(p<0.01)。此外,曲马多的腹腔内每日注射显著抑制了 DRG 中 CGRP 的表达(p<0.0001)。与 Sham 组相比,MIA+Vehicle 和 MIA+Tramadol 组的软骨减少和退化明显(p<0.0001)。有趣的是,与 MIA+Vehicle 组相比,MIA+Tramadol 组的 OA 变化明显进展(p<0.0001)。