title: The effects of intraganglionic injection of calcium/calmodulin-dependent protein kinase II inhibitors on pain-related behavior in diabetic neuropathy.
abstract: Calcium/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the transmission of nociceptive input in diabetic neuropathy. The aim of this study was to test whether intraganglionic (i.g.) injection of CaMKII inhibitors may alleviate pain-related behavior in diabetic rats. Diabetes was induced in Sprague-Dawley rats using 55 mg/kg streptozotocin intraperitoneally. Two weeks after diabetes induction, CaMKII inhibitors myristoil-AIP and KN93 were injected directly into the right L5 dorsal root ganglion (DRG). Behavioral testing with mechanical and thermal stimuli was performed before induction of diabetes, the day preceding the injection, as well as 2 and 24h after the i.g. injection. The expression of total CaMKII and its alpha isoform in DRG neurons was analyzed using immunohistochemistry. CaMKII inhibitors attenuated pain-related behavior in a modality-specific fashion. Attenuation of nociceptive behavior was accompanied with a corresponding decrease of CaMKII alpha expression in DRG neurons on the side of injection. A significant decrease of CaMKII alpha expression was seen in small- and medium-sized neurons. In conclusion, our study provides evidence that CaMKII inhibitors are potential pharmacological agents that should be further explored for treatment of diabetic neuropathy symptoms.
authors.affiliation: Laboratory for Pain Research, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia. Electronic address: antonia.jelicic@mefst.hr.
authors.forename: A
authors.initials: A
authors.lastname: Jelicic Kadic
authors.affiliation: Laboratory for Pain Research, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia. Electronic address: matija.boric.st@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Boric
authors.affiliation: Laboratory for Pain Research, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia. Electronic address: sandra.kostic@mefst.hr.
authors.forename: S
authors.initials: S
authors.lastname: Kostic
authors.affiliation: Laboratory for Pain Research, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia. Electronic address: ds@mefst.hr.
authors.forename: D
authors.initials: D
authors.lastname: Sapunar
authors.affiliation: Laboratory for Pain Research, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia. Electronic address: livia@mefst.hr.
authors.forename: L
authors.initials: L
authors.lastname: Puljak
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001596:Benzylamines / Q000627:therapeutic use*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007839:Functional Laterality; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000633:toxicity; D013449:Sulfonamides / Q000627:therapeutic use*; D013997:Time Factors; D000096926:Benzenesulfonamides
chemical_list: D000903:Antibiotics, Antineoplastic; D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D004791:Enzyme Inhibitors; D013311:Streptozocin; D013449:Sulfonamides; C072105:KN 93; D000096926:Benzenesulfonamides
keywords: CaMKII; DRG; KN-93; PBS; STZ; calcium/calmodulin-dependent protein kinase II; diabetes mellitus; dorsal root ganglion; i.g.; intraganglionic; mAIP; myristoil-AIP; myristoylated autocamtide-2-related inhibitory peptide; pain-related behavior; phosphate-buffered saline; streptozotocin; tCaMKII; total CaMKII