Activation of protein kinase B/Akt signaling pathway contributes to mechanical hypersensitivity induced by capsaicin

Rui Qing Sun, Yi Jun Tu, Jing Yin Yan, William D. Willis

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

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 1 h. 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.

Original languageEnglish (US)
Pages (from-to)86-96
Number of pages11
JournalPain
Volume120
Issue number1-2
DOIs
StatePublished - Jan 2006

Keywords

  • Capsaicin
  • Dorsal horn
  • Pain
  • Phosphoinositide 3-kinase
  • Phosphorylation
  • Protein kinase

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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