Activation of protein kinase B/Akt in the periphery contributes to pain behavior induced by capsaicin in rats.
Protein kinase B (PKB/Akt) is a member of the second-messenger regulated subfamily of protein kinases. It is implicated in signaling downstream of growth factors, insulin receptor tyrosine kinases and phosphoinositide 3-kinase (PI3K). Current studies indicate that nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and PI3K help mediate inflammatory hyperalgesia. However, little is known about the role of PKB/Akt in the nociceptive system. In this study, we investigated whether PKB/Akt in primary sensory neurons is activated after noxious stimulation and contributes to pain behavior induced in rats by capsaicin. We demonstrated that phospho-PKB/Akt (p-PKB/Akt) is increased in dorsal root ganglia (DRG) at 5 min after intradermal injection of capsaicin. p-PKB/Akt is distributed predominantly in small- and medium-sized DRG cells. After capsaicin injection, p-PKB/Akt (473) is colocalized with isotectin-B4 (IB4), tyrosine kinase A (TrkA), and calcitonin gene-related peptide (CGRP). Furthermore, most transient receptor potential vanilloid type 1 (TRPV1) positive DRG neurons double label for p-PKB/Akt. Behavioral experiments show that intradermal injection of a PI3K (upstream of PKB/Akt) inhibitor, wortmannin, dose-dependently inhibits the changes in exploratory behavior evoked by capsaicin injection. The PKB/Akt inhibitor, Akt inhibitor IV, has the same effect. The results suggest that the PKB/Akt signaling pathway in the periphery is activated by noxious stimulation and contributes to pain behavior.
Sun
R
R
Department of Neuroscience and Cell Biology, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-1069, USA.
Yan
J
J
Willis
W D
WD
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D002211:Capsaicin / Q000494:pharmacology*; D004789:Enzyme Activation / Q000502:physiology; D005106:Exploratory Behavior / Q000187:drug effects; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D007150:Immunohistochemistry; D007271:Injections, Intradermal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009475:Neurons, Afferent / Q000187:drug effects / Q000201:enzymology; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000378:metabolism* / Q000523:psychology*; D017933:Peripheral Nervous System / Q000187:drug effects / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009419:Nerve Tissue Proteins; D051057:Proto-Oncogene Proteins c-akt; D002211:Capsaicin