5-HT7 receptor activation attenuates thermal hyperalgesia in streptozocin-induced diabetic mice |
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Authors: | Ulugol Ahmet Oltulu Cagatay Gunduz Ozgur Citak Cihad Carrara Roberto Shaqaqi Mohammad Reza Sanchez Alicia Mansilla Dogrul Ahmet |
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Affiliation: | a Department of Medical Pharmacology, Faculty of Medicine, Trakya University, 22030-Edirne, Turkeyb Faculty of Medicine and Surgery, University of Studies of Pavia, Pavia 27100, Italyc Tehran University of Medical Sciences, Tehran, Irand Life and Health Sciences Faculty, Pompeu Fabra University, Barcelona, Spaine Department of Medical Pharmacology, Gulhane Military Academy of Medicine, 06018-Ankara, Turkey |
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Abstract: | The role of 5-HT7 receptors in the nociceptive processing received most attention during the last few years. The involvement of 5-HT7 receptors in nerve injury-induced neuropathic pain states have been reported only recently; however, there are no reports on its contribution in diabetic neuropathic pain. We therefore planned to investigate the effect of 5-HT7 receptor activation on the changes of nociceptive threshold in diabetic mice. Diabetes was induced by a single intraperitoneal injection of streptozocin (150 mg/kg, i.p.). The nociceptive responses in normal and diabetic animals were tested in the hot-plate and tail-flick assays. Both hot-plate and tail-flick latencies significantly shortened at 1-3/4 weeks (thermal hyperalgesia) and prolonged at 6-7 weeks (thermal hypoalgesia) after streptozocin administration. At the dose of 10 mg/kg, systemic injections of AS-19, a selective 5-HT7 receptor agonist, reduced thermal hyperalgesia at early stage of diabetes, but did not influence thermal hypoalgesia at late stage. Co-administration of SB-258719, a selective 5-HT7 receptor antagonist, at a dose that had no effect on its own (10 mg/kg), reversed the anti-hyperalgesic effect of AS-19. Our results indicate that systemic administration of 5-HT7 receptor agonists may have clinical utility in treating diabetic neuropathic pain. |
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Keywords: | Diabetes Thermal hyperalgesia Thermal hypoalgesia Serotonin 5-HT7 receptors |
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