Rijsdijk Mienke, Agalave Nilesh M, van Wijck Albert J M, Kalkman Cornelis J, Ramachandran Roshni, Baharpoor Azar, Svensson Camilla I, Yaksh Tony L
Department of Anesthesiology, University Medical Center Utrecht, The Netherlands.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Scand J Pain. 2017 Jul;16:1-9. doi: 10.1016/j.sjpain.2016.12.008. Epub 2017 Feb 3.
Despite widespread use, the efficacy of neuraxial glucocorticoids for neuropathic pain is subject to debate. Since most glucocorticoid actions are mediated through its receptor, we explored the effects of intrathecal methylprednisolone acetate (MPA) on total glucocorticoid receptor (tGR) levels and activation of the glucocorticoid receptor (phosphorylated state=pGR) within the spinal dorsal horn (SDH) and dorsal root ganglion (DRG) in a spinal nerve ligation (SNL) model in rats.
Rats received unilateral ligation of the L5/L6 spinal nerves and were treated with two intrathecal doses of either 400μg MPA or 0.9% saline with a 72-h interval. Plantar tactile thresholds were measured over time. Seven days after drug treatment, DRG and SDH were harvested to assess tGR and pGR levels using immunohistochemistry and qPCR.
Allodynia, defined by lowered tactile withdrawal thresholds after SNL, was unaltered by intrathecal MPA. In saline controls, mRNA levels of tGR did not change after SNL in the DRGs or SDH. tGR and pGR protein levels in the SDH however, significantly increased on the ipsilateral side of SNL compared to the contralateral side and to naïve tissue. When treating rats with MPA, tGR mRNA levels were significantly reduced in the SDH compared to saline controls. tGR and pGR protein levels, however were not significantly lower compared to saline controls.
In intrathecal MPA treated rats, tGR mRNA levels decreased after SNL. However this did not result in lower tGR and pGR protein levels compared to saline controls, and did not decrease ligation-induced mechanical hypersensitivity.
Intrathecal MPA treatment after SNL did not result in lower tGR and pGR levels within the SDH and DRG compared to saline controls. In present study we did not differentiate between the various isoforms of the GR which might clarify this finding.
尽管神经轴糖皮质激素在临床上广泛应用，但其治疗神经性疼痛的疗效仍存在争议。由于大多数糖皮质激素的作用是通过其受体介导的，我们在大鼠脊神经结扎（SNL）模型中，探讨了鞘内注射醋酸甲泼尼龙（MPA）对脊髓背角（SDH）和背根神经节（DRG）中糖皮质激素总受体（tGR）水平以及糖皮质激素受体激活状态（磷酸化状态=pGR）的影响。
大鼠接受L5/L6脊神经单侧结扎，并于72小时的间隔后接受两次鞘内注射，分别注射400μg MPA或0.9%生理盐水。随时间测量足底触觉阈值。药物治疗7天后，采集DRG和SDH，采用免疫组织化学和定量聚合酶链反应（qPCR）评估tGR和pGR水平。
SNL后触觉撤离阈值降低所定义的异常性疼痛，未因鞘内注射MPA而改变。在生理盐水对照组中，SNL后DRG或SDH中tGR的mRNA水平未发生变化。然而，与对侧和未处理组织相比，SNL同侧SDH中的tGR和pGR蛋白水平显著升高。与生理盐水对照组相比，用MPA治疗大鼠时，SDH中tGR的mRNA水平显著降低。然而，tGR和pGR蛋白水平与生理盐水对照组相比并无显著降低。
在鞘内注射MPA治疗的大鼠中，SNL后tGR的mRNA水平降低。然而，与生理盐水对照组相比，这并未导致tGR和pGR蛋白水平降低，也未减轻结扎诱导的机械性超敏反应。
与生理盐水对照组相比，SNL后鞘内注射MPA治疗并未导致SDH和DRG中tGR和pGR水平降低。在本研究中，我们未区分糖皮质激素受体的各种亚型，这可能有助于阐明这一发现。
