The Respective and Interaction Effects of Spinal GRs and MRs on Radicular Pain Induced by Chronic Compression of the Dorsal Root Ganglion in the Rat

High levels of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) are colocalized in the substantia gelatinosa. This indicates that the pain pathways appear to be under a strong regulation of these receptors. However, their respective effects on pain behaviors and their interaction remain unclear. Here we show that the nociceptive behaviors induced by chronic compression of the lumbar dorsal root ganglion (CCD) are attenuated by either GR agonist dexamethasone (4=2 μg>vehicle) or MR antagonist spironolactone (3 μg) administered intrathecally twice daily for postoperative days 2-4, whereas the GR antagonist mifepristone (2 μg) significantly exacerbated both mechanical hyperalgesia and thermal allodynia. Co-administration of spironolactone (3 μg) with dexamethasone (2 μg or 4 μg) twice daily on days 2-4 after CCD surgery produced positive synergistic effects. Moreover, different from intrathecally administered dexamethasone alone [no difference was found between two dose levels of dexamethasone (4 μg=2 μg)], dexamethasone suppresses mechanical allodynia and thermal hyperalgesia in a dose-dependent manner (4 μg>2 μg>vehicle) when combined with spironolactone (3 μg). These findings indicate that both central GRs and MRs play an important role in the regulation of pain behaviors and they have a perplexing interaction with each other. Spironolactone can enhance the analgesic effects of dexamethasone via complex mechanisms.