title: Effect of bucladesine, pentoxifylline, and H-89 as cyclic adenosine monophosphate analog, phosphodiesterase, and protein kinase A inhibitor on acute pain.
abstract: The aim of this study was to determine the effects of cyclic adenosine monophosphate (cAMP) and its dependent pathway on thermal nociception in a mouse model of acute pain. Here, we studied the effect of H-89 (protein kinase A inhibitor), bucladesine (Db-cAMP) (membrane-permeable analog of cAMP), and pentoxifylline (PTX; nonspecific phosphodiesterase (PDE) inhibitor) on pain sensation. Different doses of H-89 (0.05, 0.1, and 0.5 mg/100 g), PTX (5, 10, and 20 mg/100 g), and Db-cAMP (50, 100, and 300 nm/mouse) were administered intraperitoneally (I.p.) 15 min before a tail-flick test. In combination groups, we injected the first and the second compounds 30 and 15 min before the tail-flick test, respectively. I.p. administration of H-89 and PTX significantly decreased the thermal-induced pain sensation in their low applied doses. Db-cAMP, however, decreased the pain sensation in a dose-dependent manner. The highest applied dose of H-89 (0.5 mg/100 g) attenuated the antinociceptive effect of Db-cAMP in doses of 50 and 100 nm/mouse. Surprisingly, Db-cAMP decreased the antinociceptive effect of the lowest dose of H-89 (0.05 mg/100 g). All applied doses of PTX reduced the effect of 0.05 mg/100 g H-89 on pain sensation; however, the highest dose of H-89 compromised the antinociceptive effect of 20 mg/100 g dose of PTX. Co-administration of Db-cAMP and PTX increased the antinociceptive effect of each compound on thermal-induced pain. In conclusion, PTX, H-89, and Db-cAMP affect the thermal-induced pain by probably interacting with intracellular cAMP and cGMP signaling pathways and cyclic nucleotide-dependent protein kinases.
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Science Research Center, Tehran University of Medical Science, PO Box 14155-6451, Tehran, Iran.
authors.forename: Forouz
authors.initials: F
authors.lastname: Salehi
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Science Research Center, Tehran University of Medical Science, PO Box 14155-6451, Tehran, Iran.|Department of Biology and Biochemistry, University of Houston, Houston, TX, 77204, USA.
authors.forename: Mahshid S
authors.identifier: http://orcid.org/0000-0002-9202-6472
authors.initials: MS
authors.lastname: Hosseini-Zare
authors.affiliation: Department of Biomedical Engineering, University of Houston, Houston, TX, 77204, USA.
authors.forename: Haleh
authors.initials: H
authors.lastname: Aghajani
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Science Research Center, Tehran University of Medical Science, PO Box 14155-6451, Tehran, Iran.
authors.forename: Seyedeh Yalda
authors.initials: SY
authors.lastname: Seyedi
authors.affiliation: Department of Biomedical Engineering, University of Houston, Houston, TX, 77204, USA.
authors.forename: Maryam S
authors.initials: MS
authors.lastname: Hosseini-Zare
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Science Research Center, Tehran University of Medical Science, PO Box 14155-6451, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sharifzadeh
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D059787:Acute Pain / Q000188:drug therapy / Q000201:enzymology; D003994:Bucladesine / Q000494:pharmacology / Q000627:therapeutic use; D000242:Cyclic AMP / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D007546:Isoquinolines / Q000494:pharmacology / Q000627:therapeutic use; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D010431:Pentoxifylline / Q000494:pharmacology / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D003994:Bucladesine; D000242:Cyclic AMP; D007546:Isoquinolines; D010431:Pentoxifylline; D010726:Phosphodiesterase Inhibitors; D013449:Sulfonamides; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
keywords: 
  cGMP
  ; cyclic adenosine monophosphate; pain; phosphodiesterase inhibitor; protein kinase A