Increase in Reactive Oxygen Species and Activation of Akt Signaling Pathway in Neuropathic Pain

• Published in: Cellular and molecular neurobiology 2008-12, Vol.28 (8), p.1049-1056
• Main Authors: Guedes, Renata P, Araújo, Alex S. R, Janner, Daiane, Belló-Klein, Adriane, Ribeiro, Maria Flávia M, Partata, Wania A
• Format: Article
• Language: English
• Subjects: Aldehydes - metabolism; Animals; Biomedical and Life Sciences; Biomedicine; Blotting, Western; Cell Biology; Enzyme Activation; Hydrogen Peroxide - metabolism; Male; Neuralgia - enzymology; Neuralgia - pathology; Neurobiology; Neurosciences; Original Paper; Phosphoproteins - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Signal Transduction; Spinal Cord - enzymology; Spinal Cord - pathology
• ISSN: 0272-4340; 1573-6830; 1573-6830
• DOI: 10.1007/s10571-008-9279-9

Neuropathic pain occurs as a result of peripheral or central nervous system injury. Its pathophysiology involves mainly a central sensitization mechanism that may be correlated to many molecules acting in regions involved in pain processing, such as the spinal cord. It has been demonstrated that reactive oxygen species (ROS) and signaling molecules, such as the serine/threonine protein kinase Akt, are involved in neuropathic pain mechanisms. Thus, the aim of this study was to provide evidence of this relationship. Sciatic nerve transection (SNT) was used to induce neuropathic pain in rats. Western blot analysis of Akt and 4-hydroxy-2-nonenal (HNE)-Michael adducts, and measurement of hydrogen peroxide (H₂O₂) in the lumbosacral spinal cord were performed. The main findings were found seven days after SNT, when there was an increase in HNE-Michael adducts formation, total and p-Akt expression, and H₂O₂ concentration. However, one and 15 days after SNT, H₂O₂ concentration was raised in both sham (animals that were submitted to surgery without nerve injury) and SNT groups, showing the high sensibility of this ROS to nociceptive afferent stimuli, not only to neuropathic pain. p-Akt also increased in sham and SNT groups one day post injury, but at 3 and 7 days the increase occurred exclusively in SNT animals. Thus, there is crosstalk between intracellular signaling pathways and ROS, and these molecules can act as protective agents in acute pain situations or play a role in the development of chronic pain states.