title: Activation of protein kinase B/Akt signaling pathway contributes to mechanical hypersensitivity induced by capsaicin.
abstract: We investigated the involvement of the protein kinase B/Akt (PKB/Akt) signaling pathway in the mechanical hypersensitivity induced in rats by capsaicin. Intradermal injection of capsaicin results in activation of PKB/Akt in the lumbar spinal cord, most prominently in the dorsal horn, starting by 5 min after capsaicin injection and lasting at least 1h. The activated PKB/Akt in the spinal cord is in neurons, since phospho-PKB/Akt (p-PKB/Akt) colocalizes with the neuronal marker, neuronal-specific nuclear protein (NeuN). The mechanical hypersensitivity is shown by the enhanced paw withdrawal frequency to applications of von Frey filaments with different bending forces (30, 100, 200 mN) on the rat paw. Pre-treatment with several different PKB/Akt inhibitors, including SH-6, Akt inhibitor IV, and Akt inhibitor V, blocked the mechanical hypersensitivity induced by intradermal injection of capsaicin, a measure of spinal cord central sensitization. Two structurally unrelated phosphoinositide 3-Kinase (PI3K, upstream of PKB/Akt) inhibitors, Wortmannin and LY294002, also prevented the mechanical hypersensitivity induced by intradermal injection of capsaicin. Furthermore, post-treatment with the PI3K inhibitor, Wortmannin, or PKB/Akt inhibitors, such as NL-71-101, SH-6, Akt inhibitor IV, and inhibitor V significantly reduced the established mechanical hypersensitivity induced by capsaicin. The PKB/Akt signaling pathway in the spinal cord is therefore involved in pain hypersensitivity.
authors.affiliation: Department of Neuroscience and Cell Biology, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-1069, USA.
authors.forename: Rui-Qing
authors.initials: RQ
authors.lastname: Sun
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Tu
authors.forename: Jing-Yin
authors.initials: JY
authors.lastname: Yan
authors.forename: William D
authors.initials: WD
authors.lastname: Willis
mesh_terms: D000818:Animals; D002211:Capsaicin; D002478:Cells, Cultured; D004789:Enzyme Activation; D006930:Hyperalgesia / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D020671:Posterior Horn Cells / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014110:Touch
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D002211:Capsaicin