Chronic Nerve Pain May Be Caused By Endotoxin, Commercial Food, And Pharma Drugs

haidut

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I posted a few threads last year demonstrating that some cases of chronic nerve pain may be caused by a side effects of opioids - activation of TLR4. However, that study only looked at why certain patients using opioids for severe pain go on to develop chronic pain of phantom origin. As such, the study did not look whether chronic activation of TLR4 can cause chronic nerve pain on its own, without opioid use. Well, the study below demonstrated just that. Chronically elevated levels of lysozymes, which is commonly seen in chronic low-grade endotoxemia, acts through the TLR4 receptor to cause the infamous phantom pain that so many war veterans, alcoholics, trauma survivors, patients with PTSD/depression and in general people under chronic stress report. So far, medicine has been treating such pain as psychological in origin and those poor patients have been drugged out of their mind with SSRI or antipsychotic drugs. Hopefully, as a result of this study safer approaches such cessation of opioids, antibiotics such as minocycline and other TLR4 antagonists such as naltrexone, tricyclic antidepressants, vitamin D/A, emodin, pregnenolone, etc would be considered instead.

Last but not least, the study raises some serious concerns about the safety of commercial food and pharmaceutical drugs, as lysozyme is commonly used as an ingredient in those products. Peat published an entire newsletter on the topic but its focus were nanoparticles and ingredients such as silica, titanium dioxide, food colors, etc and not enzymes. So, now apparently we have to add food-grade enzymes used in dairy and pickled food to the list of dangerous chemicals. While ingesting lysozyme(s) will likely lead to the degradation of the offending enzyme by stomach acid, in hypothyroid (or otherwise sick) people this process is greatly reduced due to the low levels of stomach acid. As such, lysozyme can "at best" be a serious allergen and at worst the food/drugs we buy from stores may be giving us the equivalent of low-grade endotoxemic reaction with all the risk that such reaction entails.

Lysozyme elicits pain during nerve injury by neuronal Toll-like receptor 4 activation and has therapeutic potential in neuropathic pain
IISc researchers discern how a protein causes chronic nerve pain

"...Chronic pain makes lives miserable, and trillions of dollars are spent globally for its treatment. Persistent nerve pain, due to damage or injury to the nerves, is one such. A quarter of diabetic patients and about 35% of people with HIV infection suffer from this shooting and burning pain. Other causes of nerve pain include cancer, chemotherapy, multiple sclerosis, accidents, surgeries, spinal cord injury, and nutrient deficiency. Although it affects about 7-10% of the world's population, the available treatment options are not very useful. Besides, since the mechanisms behind chronic nerve pain are not completely clear, it is difficult to design new drugs. In a recent study, Prof Avadhesha Surolia and Dr Saurabh Yadav from the Indian Institute of Science, Bengaluru, have described what could be causing such pain. The study, published in the journal Science Translational Medicine, also suggests some potential treatment options. The study was funded by the Council of Scientific and Industrial Research (CSIR) and the Science and Engineering Research Board. The researchers identified lysozyme, a protein found in secretions like tears, saliva and human milk as a cause for persistent nerve pain. Lysozyme is an integral component of our immune system and protects us from bacterial infection by breaking down their cell wall. It is also a commercially important enzyme used in the food and pharmaceutical sectors. Studies on rat nerve cells in the laboratory revealed that the levels of lysozyme increase in these cells after a nerve injury. The injection of lysozyme also caused nerve pain by increasing the excitability of nerve cells. These observations confirmed the role of lysozyme in causing this chronic pain. In healthy nerve cells, the levels of lysozyme are low, and it increases following a nerve injury. A receptor called toll-like receptor-4 (TLR4), present on the surface of the nerve cells, gets activated during such damages. Although TLR4's role in causing nerve pain was known, the molecular pathway for its activation was not clear."

"...Annexin A2 is another protein in the body that plays a role in inducing pain. Lysozyme interacts with annexin A2 at the surface of nerve cells and activates TLR4 receptors. The researchers found that lysozyme failed to invoke pain when annexin A2 was absent. The researchers hope that their findings could hold a clue for treating chronic nerve pain. One approach could be using compounds that inhibit lysozyme in the cells, without side effects. When the researchers injected chitobiose, a lysozyme inhibitor, they found that it relieved pain in rats with a nerve injury. Blocking lysozyme is also a safer option than targeting other molecules with a more critical role in the nerve cells. High levels of lysozyme are also found in some other nerve-related disorders like Alzheimer's, Parkinson's, and multiple sclerosis. The researchers hope that the findings of this study would form a base to explore the role of lysozyme in such nerve-related diseases."
 

Sativa

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Perhaps egg white has questionable properties...
High levels of lysozyme are also found in some other nerve-related disorders like Alzheimer's, Parkinson's, and multiple sclerosis.
Lysozyme is traditionally associated with eggs, especially chicken eggs.
Egg white contains 11% protein, and 3.5% of the egg white protein is lysozyme.
Therefore, this enzyme is among the major proteins in egg white where it serves to protect and nourish the developing embryo (Abeyrathne et al., 2013).

iirc, egg white also contains protease inhibitors.
Doesn't sound appealing.
 
Last edited:

Philomath

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Chapter 22 - Use of Hen Egg White Lysozyme in the Food Industry


Abstract
Lysozymes are a class of enzymes with antimicrobial properties that are widely found across the animal kingdom as a natural bactericide. Currently, lysozyme from the egg white of chicken eggs is the only lysozyme industrially applied for food applications. Lysozyme hydrolyses the β-1,4-glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine of peptidoglycan, the structural component of the bacterial cell walls. Lysozyme is effective mainly against Gram-positive bacteria, but its spectrum can be broadened toward Gram-negative bacteria through denaturation, chemical modifications, or by combining it with other preservatives. The safety and technological stability of lysozyme makes it an ideal preservative for food applications although European Union allergen legislation requires labeling. In cheese making, lysozyme accelerates ripening and prevents growth of Clostridiumtyrobutyricum which is responsible for late blowing and off-flavors in cheese. Lysozyme also controls growth of lactic acid bacteria in wine and beer. Different types of food can be preserved by coating their surface with lysozyme.
Use of Hen Egg White Lysozyme in the Food Industry - ScienceDirect
 

Philomath

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Perhaps egg white has questionable properties...

Maybe the yolk mixed with the white (omelette or scrambled) is nature’s preferred method of consumption.

The Influence of Yolk on Egg White Lysozyme1'2'3
MacDonnell et al. (1955) showed that the more rapid foamers in egg white were the globulins; therefore, it is possible that the harmful ef- fects of yolk in liquid egg white are caused by the complexing between certain yolk lip- ids and lysozyme and other whipping pro- teins of egg white. Further work is needed to determine the yolk component(s) re- sponsible for inactivating lysozyme and whether the reaction is reversible.
 

Philomath

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Other interesting articles:

Feeney, R.E., Macdonnell, L.R. and Ducay, E.D. (1956) Irreversible inactivation of lysozyme by copper. Archives of Biochemistry and Biophysics 61: 72–83CrossRef | Google Scholar | PubMed

Fujimaki, M., Kato, H. and Hayase, F. (1972) Studies on roasting changes of proteins. I. Changes of casein and lysozyme during roasting. Agricultural and Biological Chemistry 36: 416–425
Google Scholar

Ross, V. (1949) Precipitation of insulin by lysozyme and effect of the complex on the blood sugar level. Society for Experimental Biology, Medicine Proceedings 72: 465–468CrossRef | Google Scholar | PubMe
(The complex produces a prompt lowering of the blood-sugar level in rabbits.)

Wasserfall, F.E., Voss, E. and Prokopek, D. (1976) Studies on cheese ripening. V. The use of lysozyme instead of nitrate to inhibit late blowing of cheese. Kieler Milchwirtschaftliche Forschungsberichte 28: 3–16[URL='https://scholar.google.com/scholar_lookup?title=Studies+on+cheese+ripening.+V.+The+use+of+lysozyme+instead+of+nitrate+to+inhibit+late+blowing+of+cheese&publication+year=1976&author=Wasserfall+F.E.&author=Voss+E.&author=Prokopek+D.&journal=Kieler+Milchwirtschaftliche+Forschungsberichte&volume=28&pages=3-16']Google Scholar

Yajima, M., Hidaka, Y. and Matsuoka, Y. (1968) Studies on egg-white lysozyme as a preservative of sake. Journal of Fermentation Technology 46: 782–788Google Scholar[/URL]
[URL='https://scholar.google.com/scholar_lookup?title=Studies+on+egg-white+lysozyme+as+a+preservative+of+sake&publication+year=1968&author=Yajima+M.&author=Hidaka+Y.&author=Matsuoka+Y.&journal=Journal+of+Fermentation+Technology&volume=46&pages=782-788']
Yashitake, S. and Shinichiro, A. (1977) Use of egg-white lysozyme in the food industry. New Food Industry 19: 17–23
[/URL]Google Scholar
[URL='https://scholar.google.com/scholar_lookup?title=Studies+on+egg-white+lysozyme+as+a+preservative+of+sake&publication+year=1968&author=Yajima+M.&author=Hidaka+Y.&author=Matsuoka+Y.&journal=Journal+of+Fermentation+Technology&volume=46&pages=782-788']
Consumption of Lysozyme-Rich Milk Can Alter Microbial Fecal Populations
Elizabeth A. Maga, Prerak T. Desai, [...], and James D. Murray
[URL="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3416601/"]Consumption of Lysozyme-Rich Milk Can Alter Microbial Fecal Populations

We demonstrated that consumption of lysozyme-rich milk indeed altered gut microbiota populations and shifted the microbial population to those microbes associated with activities beneficial for the host.[/URL][/URL]



 
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