title: 5-HT7 receptor activation attenuates thermal hyperalgesia in streptozocin-induced diabetic mice.
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.
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Trakya University, 22030-Edirne, Turkey. aulugol@trakya.edu.tr
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ulugol
authors.forename: Cagatay
authors.initials: C
authors.lastname: Oltulu
authors.forename: Ozgur
authors.initials: O
authors.lastname: Gunduz
authors.forename: Cihad
authors.initials: C
authors.lastname: Citak
authors.forename: Roberto
authors.initials: R
authors.lastname: Carrara
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Shaqaqi
authors.forename: Alicia Mansilla
authors.initials: AM
authors.lastname: Sanchez
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dogrul
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010880:Piperidines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013311:Streptozocin; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013311:Streptozocin; D013449:Sulfonamides; C111309:3,N-dimethyl-N-(1-methyl-3-(4-methylpiperidin-1-yl)propyl)benzenesulfonamide; D000096926:Benzenesulfonamides; C104425:serotonin 7 receptor