Cytokines are then released and act back on neurons to facilitate central sensitization, activated glial cells are a source of cytokines. The present study demonstrates interactions between microglia and neurons through proinflammatory cytokines and NMDAR coupling in central hyperexcitability and inflammatory hyperalgesia. The expressions of several proinflammatory cytokines, as revealed by western blot experiments in our present study, are considerably increased following chronic compression of the dorsal root ganglia. Our previous experiment also revealed a notable up regulation of Ikb-a in the early stage of radicular pain. The PLX4032 expression of Ikb-a parallels with NF-kb activity, which has been proposed to be a reliable marker for cytokine-responsive cells within the central nervous system. While no overt tissue inflammation and edema occurred at the spinal level, together with the expression of NF-kb in the superficial dorsal horn, on the contrary, shown marked decrease after peripheral nerve injury. Moreover, epidural or intrathecal administration with anti-inflammatory glucocorticoids exerted beneficial effects on pain behaviors and significantly decreased the expression of NMDA receptor in the superficial dorsal horn and DRG after chronic compression of the dorsal root ganglia, whereas intrathecal treatment with dexamethasone exacerbated neuropathic pain behaviors after peripheral nerve injury. Correlated with their study, the expression of NMDA receptor did not change after intrathecal injection of spironolactone. These opposing results further confirm that the anti-inflammatory potency of spironolactone in the superficial dorsal horn and DRG is implicated in the mechanism for which beneficial effects on radicular pain behaviors are involved. A large body of animal and clinical studies also reported that spironolactone has potent anti-inflammatory effects in multiple organs and systems via mineralocorticoid receptor or nonmineralocorticoid receptor mechanisms. For example, first, in principal cells of the cortical collecting duct, spironolactone attenuated aldosterone-induced inflammatory cytokines production such as IL-1b and IL-6 via mineralocorticoid receptordependent pathway, second, in human mononuclear cells, spironolactone inhibited the activation of NF-kb and the expression of several NF-kb-targeted genes via non-mineralocorticoid receptor mechanisms, third, in rheumatoid arthritis patients, treatment with spironolactone improves both endothelial dysfunction and inflammatory disease activity. In our present study, we also found a robust anti-inflammatory effect of spironolactone. However, whether these effects are mineralocorticoid receptor-dependent or non-mineralocorticoid receptorrelevant need further exploration. Though an in vivo study showed that spironolactone can reduce the activation of glial cells through mineralocorticoid receptor dependent pathway, the expression of mineralocorticoid receptors in glial cells in spinal cord and DRG after CCD surgery remains to be investigated.