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Effect of bucladesine, pentoxifylline, and H‐89 as cyclic adenosine monophosphate analog, phosphodiesterase, and protein kinase A inhibitor on acute pain
Author(s) -
Salehi Forouz,
HosseiniZare Mahshid S.,
Aghajani Haleh,
Seyedi Seyedeh Yalda,
HosseiniZare Maryam S.,
Sharifzadeh Mohammad
Publication year - 2017
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12282
Subject(s) - pentoxifylline , nociception , phosphodiesterase , phosphodiesterase inhibitor , protein kinase a , pharmacology , cyclic adenosine monophosphate , endocrinology , adenosine , tail flick test , medicine , chemistry , kinase , receptor , enzyme , biochemistry
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 n m /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 n m /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.