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IISc researchers discern how a protein causes chronic nerve pain

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8 Aug 2019
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.

"Our research shows that lysozyme activates neuronal TLR4 during a nerve injury, which results in neuronal hyper-excitability and pain," explain the researchers. This observation also shows that nerve cells can detect damage.

When the researchers repeated their experiments on human nervous tissue, they found similar results. They observed increased levels of lysozyme in spinal cord tissues collected from patients with spinal cord injury. Besides, when lysozyme was applied to human nerve cells, it increased the neuronal activity—a common condition during nerve pain.

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.

"Our observation indicates the potential of lysozyme inhibitors as a safer and natural alternative for managing nerve pain," says Prof Surolia.

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.

This article has been run past the researchers, whose work is covered, to ensure accuracy.