Bengaluru scientists make a painkilling leap

In what may lead to the development of a new painkiller, two scientists at the Indian Institute of Science (IISc), Bengaluru, have found out how patients of cancer, surgery or amputation feel persistent and severe pain for weeks or months.

An understanding of the underlying biology of such pain may one day lead to the creation of a better painkiller drug as existing medicines like opioids are not preferred by doctors because of their addictive nature.

In a new study involving mice, rats and human postmortem tissues, Saurabh Yadav and Avadhesha Surolia from IISc’s Molecular Biophysics Unit detail how an enzyme that usually digests bacteria can promote chronic pain related to nerve injury.

The results will not only help explain how injuries and inflammation in neurons can increase pain sensitivity but also suggest that inhibitors of the enzyme could be potential therapies for chronic or neuropathic (felt by cancer, surgery and amputation patients) pain.

Pain can broadly be classified into two groups — inflammatory (caused by injury or infection) and neuropathic or chronic pain triggered by damage to the central or peripheral nervous system. The former can be managed by classical painkillers. But barring opioids, there is barely any option for doctors to tackle the second type of pain.

Neuropathic pain occurs when injuries to neurons alter brain cells’ excitability to feel more pain sensation. Current treatments are ineffective against such pain as its molecular mechanisms are different from inflammatory pain.

“Research in our laboratory identified lysozyme — a bacteria-eating enzyme and an important component of our immune system — as the leading contributor to the development of neuropathic pain,” Surolia told DH.

Incidentally, the enzyme was discovered in 1921 by Sir Alexander Fleming who among other things also found penicillin.

“Injections of lysozyme inhibitors resulted in pain relief in our laboratory rat models of pain. Our studies uncover a previously unknown mechanism associated with neuropathic pain along with identification of novel targets for future therapeutic interventions and could prove to be a game-changer in this area,” he noted.

Yadav and Surolia found two ways to disrupt lysozyme’s functions in the body, leading to two potential drug targets that would now be investigated in detail by the duo. They continue with the research to find which one of the two leads is better and if there are any side effects.

Besides improved health, a new painkiller would immensely contribute to improving economic productivity, as productivity worth nearly $600 billion is lost due to pain in the US (2012 estimate). The numbers for India could be in the same range or slightly higher.

The research has been published in the August 7 issue of Science Translational Medicine.