HEIRS Research: New Research Provides Stronger Link to ASIC3, Chronic Fatigue, Fibromyalgia and Inflammatory Pain~!

 

A few months back in the blog “HEIRS Environmental Illness: Intestinal Inflammation, ASIC3 and TRPV1” we made some comments about research on chronic fatigue syndrome and fibromyalgia in relation to nociception activity and more specifically to TRPV1, TRPA1 and ASICS 3.  For review purposes we discussed how tissue acidity and ASICS channels (specifically for simplification the ASIC3 channels) are involved with pain and fatigue generation in the human body and therefore could be an important mechanism in pain generation in environmental illness. In addition, we pointed out the body has mechanisms to maintain a normal acid/base balance and acidity at the cellular or tissue level is an important factor for the proper functioning of many cellular processes.  Lastly, we mentioned a study released  in early 2008 which revealed that “metabolic dyfunction, higher numbers and activation of ASIC3 channels had a link to elevated levels of chronic pain and fatigue in CFS and fibromyalgia, that pain can be ellicted by acidosis and hypoxia (Molliver) and other co-factors can modulate it (ie. testosterone) or contribute to the pain and fatigue and explain some of the gender differences in the presentation of these conditions.  In addition, “the sensitivity of ASIC3  channels can be altered, increased or decreased by environmental factors  when already exposed to inflammatory conditions and may have impact on insulin sensitivity.” (Huang)

A new study that was published in Molecular Pain provides more insight into the function of ASIC3 channels. In this study the author provides a clear explanation of the ASIC3 channels. He explains, “ASIC3 channels are the most sensitive channels to acidosis (which can be caused by inflammation) and that during inflammation, lactic acid, arachidonic acid and nitric oxide sensitize ASIC3 and that up-regulation of the ASIC3 channels are often found in inflamed human intestine and the dorsal root ganglion in neurons and chronic acidosis effects ”  ion transport, permeability, and metabolism of the intestinal absorptive cells”. (Wongdee) Past studies have supported the fact that inflammation-mediated hyperalgesia involves both tissue acidosis and sensitization of nociceptors but the exact role of the ASIC3 channel was not “conclusive”. On the other hand, evidence has shown that nerve growth factor (NGF) is a ”key element in inflammatory pain and high NGF control the genetic expression of ASIC3″. (Mamet) Yen’s study provides more insight into the fact that  “ASIC3 channels participate in the maintenance of hyperalgesia in sub-acute inflammation and mediate the process of granular formation and vasculitis in intramuscular inflammation. In addition, the researcher was “surprised” to observe that depending on the stimulus, hyperalgesia was sometimes accompanied by an up-regulation of  tetrodotoxin (TTX)-resistant sodium currents. (Yen)  Past studies have shown some evidence that these currents may have a modulatory role on neuronal sensitization and inflammatory mediator-induced hyperalgesia and lower the nociception threshold. (Gold, Khasar, Warfield)

Definition:

• ASIC channels: natural sensorys of acidic pain common to conditions of inflammation, ischaemia, lesions or tumors. (Devel)

Related Posts:

• HEIRS Environmental Illness: Intestinal Inflammation, ASIC3 and TRPV1
• HEIRS Chronic Fatigue Syndrome: LPS Is Considered a Pathway in CFS
• HEIRS  Hypothesis: The Gist of Environmental Illness
• HEIRS Cell Biology Snippets: LPS Effects Blood Brain Barrier Efflux
• HEIRS Environmental Health: LPS Endotoxins and Breathing Bad Air
• Food Safety: More About Bugs In The Gut—Their Role in Leaky Gut
• HEIRS Research: Environmental Illness, IGF-1 and Nrf2. Studies in Environmental Medicine.

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Wongdee, K., Teerapornpuntakit, J., Riengrojpitak, S., Krishnamra, N., and Charoenphandhu, N. (2009). Gene expression profile of duodenal epithelial cells in response to chronic metabolic acidosis. Molecular and cellular biochemistry, 321(1-2):173-188. http://www.citeulike.org/user/HEIRS/article/3873067