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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Jolivalt, C. G. Mixcoatl-zecuatl, T. |
| Description | Author Affiliation: Mixcoatl-Zecuatl T ( Department of Pathology, University of California, San Diego, La Jolla, CA 92093-0612, USA.) |
| Abstract | BACKGROUND AND PURPOSE: This study was designed to clarify mechanisms responsible for the anti-allodynic effects of duloxetine in diabetes. EXPERIMENTAL APPROACH: The streptozotocin-induced diabetic rat model was used to compare the efficacy of duloxetine, 5-HT, the 5-HT(2A) receptor agonist [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI)] and two antagonists (ketanserin and pruvanserin) on tactile allodynia. KEY RESULTS: Systemic or intrathecal injection of duloxetine alleviated tactile allodynia in diabetic rats. The effect of systemic duloxetine was reduced by intrathecal administration of ketanserin or pruvanserin, indicating participation of spinal 5-HT(2A) receptors in the mechanism of action of duloxetine. In contrast to spinal delivery, systemic and local peripheral injections of ketanserin or pruvanserin alleviated tactile allodynia in diabetic rats. This effect was reversed immediately after systemic or local DOI injection. CONCLUSIONS AND IMPLICATIONS: These results support the involvement of spinal 5-HT(2A) receptors in the ability of duloxetine to ameliorate painful diabetic neuropathy. Our data also suggest that the role of 5-HT(2A) receptors depends on the level of the neuraxis at which activation takes place, with peripheral activation contributing to tactile allodynia in diabetic rats, whereas spinal activation of this receptor alleviates tactile allodynia. The development of selective peripheral 5-HT(2A) receptor antagonists may offer a novel approach for the treatment of diabetic neuropathic pain. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 1 |
| Volume Number | 164 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2011-09-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Diabetic Neuropathies Drug Therapy Hyperalgesia Thiophenes Pharmacology Amphetamines Animals Diabetes Mellitus, Experimental Genetics Metabolism Duloxetine Hydrochloride Ketanserin Rats, Sprague-Dawley Receptor, Serotonin, 5-HT2A Serotonin Serotonin 5-HT2 Receptor Agonists Serotonin 5-HT2 Receptor Antagonists Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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