Central glucocorticoid receptors regulate the upregulation of spinal cannabinoid-1 receptors after peripheral nerve injury in rats.
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.
Wang
Shuxing
S
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.
Lim
Grewo
G
Mao
Ji
J
Sung
Backil
B
Yang
Liling
L
Mao
Jianren
J
D000818:Animals; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism*; D008297:Male; D020671:Posterior Horn Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012584:Sciatic Nerve / Q000293:injuries* / Q000378:metabolism*; D020426:Sciatic Neuropathy / Q000150:complications / Q000378:metabolism*; D015854:Up-Regulation
D043884:Receptor, Cannabinoid, CB1; D011965:Receptors, Glucocorticoid