Wang Shuxing, Lim Grewo, Mao Ji, Sung Backil, Yang Liling, Mao Jianren
MGH Center for Translational Pain Research, Division of Pain Medicine, WACC 324, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, 15 Parkman Street, Boston, MA 02114, USA.
Pain. 2007 Sep;131(1-2):96-105. doi: 10.1016/j.pain.2006.12.019. Epub 2007 Jan 26.
Previous studies have shown that peripheral nerve injury upregulated both glucocorticoid receptors (GR) and cannabinoid-1 receptors (CB1R) within the spinal cord dorsal horn in rats. However, the relationship between the expression of spinal GR and CB1R after nerve injury remains unclear. Here, we examined the hypothesis that the upregulation of spinal CB1R induced by chronic constriction nerve injury (CCI) in rats would be regulated by spinal GR. CCI induced the upregulation of spinal CB1R primarily within the ipsilateral spinal cord dorsal horn as revealed by Western blot and immunohistochemistry. The expression of CB1R in CCI rats was substantially attenuated by intrathecal treatment with either the GR antagonist RU38486 or a GR antisense oligonucleotide given twice daily for postoperative day 1-6, whereas the expression of spinal CB1R was enhanced following intrathecal administration of a GR sense oligonucleotide twice daily for postoperative day 1-6. Furthermore, the upregulation of spinal CB1R after nerve injury was prevented in adrenalectomized rats, which was at least partially restored with the intrathecal administration of an exogenous GR agonist dexamethasone, indicating that corticosteroids (endogenous GR agonists) were critical to spinal GR actions. Since the development of neuropathic pain behaviors in CCI rats was attenuated by either RU38486 or a GR antisense oligonucleotide, these results suggest that CB1R is a downstream target for spinal GR actions contributory to the mechanisms of neuropathic pain.
先前的研究表明，周围神经损伤会使大鼠脊髓背角内的糖皮质激素受体（GR）和大麻素-1受体（CB1R）均上调。然而，神经损伤后脊髓GR与CB1R表达之间的关系仍不清楚。在此，我们检验了这样一个假说，即大鼠慢性压迫性神经损伤（CCI）诱导的脊髓CB1R上调将受脊髓GR调控。如蛋白质印迹法和免疫组织化学所示，CCI主要在同侧脊髓背角内诱导脊髓CB1R上调。在术后第1 - 6天每天给予GR拮抗剂RU38486或GR反义寡核苷酸鞘内注射后，CCI大鼠中CB1R的表达显著减弱，而在术后第1 - 6天每天给予GR正义寡核苷酸鞘内注射后，脊髓CB1R的表达增强。此外，在肾上腺切除的大鼠中，神经损伤后脊髓CB1R的上调受到抑制，鞘内注射外源性GR激动剂地塞米松至少部分恢复了这种上调，这表明皮质类固醇（内源性GR激动剂）对脊髓GR的作用至关重要。由于RU38486或GR反义寡核苷酸减弱了CCI大鼠神经性疼痛行为的发展，这些结果表明CB1R是脊髓GR作用的下游靶点，对神经性疼痛机制有作用。
