Injury to the spinal nerves of mice induces mechanical allodynia and thermal hyperalgesia. In the injured spinal cord, the expression of glucocorticoid receptor mRNA was increased, whereas it was decreased in N-type Ca2+-channel-deficient mice, in which neuropathic pain is eliminated. Intrathecal and intraperitoneal injection of the glucocorticoid receptor antagonist RU486 produced antinociceptive effects, whereas intracerebroventricular injection was without effect. The more selective antagonist dexamethasone 21-mesylate suppressed both mechanical allodynia and thermal hyperalgesia. These results suggest that spinal glucocorticoid receptors play an important role in neuropathic pain, and that controlling the activity of glucocorticoid receptors may be of great importance in the treatment of neuropathic pain. (c) 2005 Elsevier B.V. All rights reserved.