Increase in Reactive Oxygen Species and Activation of Akt Signaling Pathway in Neuropathic Pain |
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Authors: | Renata P Guedes Alex S R Araújo Daiane Janner Adriane Belló-Klein Maria Flávia M Ribeiro Wania A Partata |
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Institution: | (1) Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, UFRGS, Rua Sarmento Leite, 500, 90050-170 Porto Alegre, RS, Brazil |
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Abstract: | 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. |
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Keywords: | Neuropathic pain Spinal cord Sciatic nerve transection 4-hydroxy-2-nonenal Akt Hydrogen peroxide |
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