Nitroxidative Signaling Mechanisms in Pathological Pain

[voner]

New paper from some top-notch researchers. I am still reading it.. here is the abstract..

Nitroxidative Signaling Mechanisms in Pathological Pain

Peter M. Grace,1,4,* Andrew D. Gaudet,1 Vasiliki Staikopoulos,2

Steven F. Maier,1 Mark R. Hutchinson,2 Daniela Salvemini,3 and Linda R. Watkins1


Tissue injury can initiate bidirectional signaling between neurons, glia, and

immune cells that creates and amplifies pain. While the ability for neurotrans-

mitters, neuropeptides, and cytokines to initiate and maintain pain has been

extensively studied, recent work has identified a key role for reactive oxygen and

nitrogen species (ROS/RNS; nitroxidative species), including superoxide, per-

oxynitrite, and hydrogen peroxide. In this review we describe how nitroxidative

species are generated after tissue injury and the mechanisms by which they

enhance neuroexcitability in pain pathways. Finally, we discuss potential ther-

apeutic strategies for normalizing nitroxidative signaling, which may also

enhance opioid analgesia, to help to alleviate the enormous burden of pathological pain.

http://www.cell.com/trends/neurosciences/pdf/S0166-2236(16)30140-0.pdf

 

[Navid]

New paper from some top-notch researchers. I am still reading it.. here is the abstract..




http://www.cell.com/trends/neurosciences/pdf/S0166-2236(16)30140-0.pdf

Anyway to read this free of charge. Especially interested in potential "treatments".

Thanks

 

[voner]

Anyway to read this free of charge. Especially interested in potential "treatments".

Thanks

@Navid,

try putting the "DOI" number into this site:

http://sci-hub.ac/

The "DOI" number is:

http://dx.doi.org/10.1016/j.tins.2016.10.003

 

[Navid]

Thanks, this did work and I was able to access article. Really appreciate your help! Over my head; though it does seem interesting that chronic pain affects mito function and could be reason why I became so ill after developing chronic jaw pain.

Can you explain any therapeutic approaches to impacting pain or illness? Any help in understanding greatly appreciated.

Thanks!!!

 

[CFS_for_19_years]

Thanks, this did work and I was able to access article. Really appreciate your help! Over my head; though it does seem interesting that chronic pain affects mito function and could be reason why I became so ill after developing chronic jaw pain.

Can you explain any therapeutic approaches to impacting pain or illness? Any help in understanding greatly appreciated.

Thanks!!!

From the article (bolding mine):

Indirect antioxidants augment the redox response without being antioxidants themselves. For
example, sulforaphane, resveratrol, and curcumin induce nuclear translocation of Nrf2, a
transcription factor responsible for the production of a wide array of antioxidants, and attenuate
nociceptive hypersensitivity in neuropathic pain models.[....]
exercise increases Nrf2 expression
and promotes the expression of antioxidants in the CNS as well as peripherally
Consequently, voluntary wheel running has been shown to both prevent and reverse neuro-
pathic pain.

 

[lansbergen]

Mitochondrial DNA is a target of oxidation and nitration, while peroxidated lipid end-products,
such as reactive aldehydes, can form covalent modifications (adducts) with an array of mito-
chondrial proteins, including antioxidants [92,93] . Together, these changes impair the structural
integrity and function of mitochondria.

 

[voner]

Lessons from the failure of direct antioxidants to improve clinical disease need to be recognized

within the pain field: the effects of direct antioxidants on preclinical pain models continue to be

reported despite the strong probability that the results will not translate clinically. Several studies

suggest that more-robustly engaging antioxidant systems after injury can help alleviate to pain:

for instance, in animal pain models, increasing the action of master antioxidant transcription

factors Nrf2 or FoxO, or activating the heme-oxygenase system, show promising pain-relieving

effects. Future studies could explore whether combinatorial strategies – aimed at boosting

multiple antioxidants or targeting both antioxidant and nitroxidative systems simultaneously –

dampen inflammation and pain. Nitroxidant dysregulation clearly contributes to neuropathology;

thus, discovering new targets and therapies that restore nitroxidative balance could help to

relieve pathological pain.

 

[Snowdrop]

For those with science backgrounds, there would be much gratitude for a Idiot's guide rendering of the main points and what they might imply for people in pain.

 

[Navid]

From the article (bolding mine):

Thank you!