Effects of glucocorticoid receptor antagonists on allodynia and hyperalgesia in mouse model of neuropathic pain.
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 Ca(2+)-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.
Takasaki
Ichiro
I
Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Japan.
Kurihara
Takashi
T
Saegusa
Hironao
H
Zong
Shuqin
S
Tanabe
Tsutomu
T
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D020864:Calcium Channels, N-Type / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D003907:Dexamethasone / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D006930:Hyperalgesia / Q000209:etiology / Q000517:prevention & control*; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015735:Mifepristone / Q000008:administration & dosage / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009437:Neuralgia / Q000209:etiology / Q000517:prevention & control*; D020411:Oligonucleotide Array Sequence Analysis; D010146:Pain / Q000209:etiology / Q000517:prevention & control*; D017288:Pain Threshold / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors* / Q000502:physiology; D013119:Spinal Cord Injuries / Q000150:complications / Q000235:genetics; D013997:Time Factors
D020864:Calcium Channels, N-Type; D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003907:Dexamethasone; C031710:dexamethasone 21-methanesulfonate