Peroxynitrite and Opiate Antinociceptive Tolerance: A Painful Reality, Daniela Salvemini, 2010

[Violeta]

Why haven't drug companies been working on pain relievers based on this information?

"The objectives of this first mini-review written on peroxynitrite and morphine antinociceptive tolerance are to discuss the importance of nitroxidative stress in this process and argue that peroxynitrite is a rational target for therapeutic intervention in pain management. These concepts provide a pharmacological basis for developing inhibitors of peroxynitrite biosynthesis as novel non-narcotic analgesics, thus addressing a large and currently unmet medical need with major socioeconomic consequences."

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC2714174/

 

[Pyrrhus]

Thanks for posting this (Salvemini, 2009) paper!

 

[Violeta]

Isn't that great! I have to study it later.

PS: Oops, I had forgotten the author and date.

Oh, no, I had put it in the header.

 

[Violeta]

"In addition to the 3 routes of reducing ONOO- toxicity depicted in Figure 1,"

These 3 routes are SOD, superoxide dismutase
NOS nitric oxide synthase inhibitors
OONO decomposition catalysts

"there is a fourth: scavenging of the radicals from ONOOH (urate, methionine and tyrosine peptides are examples in this category)."

 

[Violeta]

To be clear, the study's information about peroxynitrite is its effect on opioid tolerance. I am reading it for information about how to deal with peroxynitrite.

Some quotes from the study that I found interesting.


"Increased levels of glutamate (in the brain) can be decreased by reducing the production of cytokines such as TNF-α and IL-6 that have been shown to inhibit glutamate uptake. Since peroxynitrite increases cytokine production (vide infra) it is likely that peroxynitrite modulates glutamate homeostasis via the cytokine signaling pathway."

"Peroxynitrite is a potent pro-inflammatory nitroxidative species with an established role in “neuronal inflammation” (defined here as neuroimmune activation which includes activation of glial cells and release of proinflammatory cytokines)"

"In inflammation, peroxynitrite induces endothelial cell damage and increased microvascular permeability, activates redox-sensitive transcription factors including NF-κ B and AP-1 that in turn regulate genes encoding various pro-inflammatory and pronociceptive cytokines genes such as interleukin-1β, tumor necrosis factor-α and interleukin-6 (IL-1β, TNF-α and IL-6 respectively)."

"auto-catalyzes the destruction of neurotransmitters and hormones such as norepinephrine and epinephrine"