title: Calcium-calmodulin-dependent protein kinase II contributes to spinal cord central sensitization.
abstract: Calcium/calmodulin-dependent protein kinase II (CaMK II) is found throughout the CNS. It regulates calcium signaling in synaptic transmission by phosphorylating various proteins, including neuronal membrane receptors and intracellular transcription factors. Inflammation or injuries to peripheral tissues cause long-lasting increases in the responses of central nociceptive neurons to innocuous and noxious stimuli. This change can occur independently of alterations in the responsiveness of primary afferent neurons and has been termed central sensitization. Central sensitization is a form of activity-dependent plasticity and results from interactions in a set of intracellular signaling pathways, which modulate nociceptive transmission. Here we demonstrate an increased expression and phosphorylation of CaMK II in rat spinal dorsal horn neurons after noxious stimulation by intradermal injection of capsaicin. Local administration of a CaMK II inhibitor in the spinal cord significantly inhibits the enhancement of responses of spinal nociceptive neurons and changes in exploratory behavior evoked by capsaicin injection. In addition, spinal CaMK II activity enhances phosphorylation of AMPA receptor GluR1 subunits during central sensitization produced by capsaicin injection. This study reveals that CaMK II contributes to central sensitization in a manner similar to its role in the processes underlying long-term potentiation.
authors.affiliation: Department of Anatomy and Neurosciences, Marine Biomedical Institute, The University of Texas Medical Branch, Galveston, Texas 77555-1069, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Fang
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.forename: William D
authors.initials: WD
authors.lastname: Willis
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001596:Benzylamines / Q000008:administration & dosage; D015153:Blotting, Western; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002211:Capsaicin; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism*; D007150:Immunohistochemistry; D007278:Injections, Spinal; D008297:Male; D017551:Microdialysis; D010147:Pain Measurement / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013449:Sulfonamides / Q000008:administration & dosage; D000096926:Benzenesulfonamides
chemical_list: D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002211:Capsaicin; D004791:Enzyme Inhibitors; D018091:Receptors, AMPA; D013449:Sulfonamides; C425780:KN 92; C072105:KN 93; D000096926:Benzenesulfonamides