‘Pain Sensor’ Discovery Could Lead To New Painkillers

A protein in the membrane of our sensory neurons is involved in our capacity to feel mechanical pain, according to a new study. The finding lays the foundation for the development of powerful new analgesic drugs, researchers report.

The research is the first to show that TACAN, a highly conserved protein among vertebrates whose function remained unclear, is in fact involved in detecting mechanical pain by converting mechanical pressures into electric signals.

Using molecular and cellular approaches with electrophysiology, senior author Reza Sharif-Naeini, a professor in the physiology department at McGill University, and his team found TACAN on the membrane of pain sensing cells where it forms tunnel-like pores, a structure known as an ion channel. The researchers also created a mouse model where they could “turn off” TACAN, making the animals significantly less sensitive to painful mechanical stimuli.

Mechanotransduction

About 70 years ago, scientists imagined that tiny sensors might be responsible for providing our brain with useful information about our environment, explaining our sense of touch or our capacity to feel pain when pinched.

These sensors have since been discovered to be ion channels — pore like structures capable of translating mechanical pressures exerted on a cell into electrical signals that travel to the brain to be processed — a phenomenon known as mechanotransduction.

Researchers have shown this phenomenon to be central in several physiological processes such as hearing, touch, and the sensation of thirst. But the identity of the sensor responsible for mechanical pain remained elusive.

Because most of the pain we feel — a pinch or a stubbed toe — is mechanical in nature, Sharif-Naeini says that competition to find the newly discovered sensor was fierce.

We Need A New Drug

With the rampant problem of opioid overuse, the finding has practical implications for people who suffer from chronic pain.

Patients with conditions such as osteoarthritis, rheumatoid arthritis, or neuropathic pain often develop mechanical allodynia, a condition where mechanical pain receptors become overly sensitive. Trivial things such as walking or a light touch thus become extremely painful, leading to a significant reduction in the quality of their lives.

“Now that we have identified the sensor associated with mechanical pain, we can start designing new powerful analgesic drugs that can block its action. This discovery is really exciting and brings new hope for novel pain treatment,”

adds Sharif-Naeini.

Support for this work came from the Canadian Institutes of Health Research and the Groupe d’étude des protéines membranaires.

[1] Lou Beaulieu-Laroche, Marine Christin, Annmarie Donoghue, Francina Agosti, Noosha Yousefpour, Hugues Petitjean, Albena Davidova, Craig Stanton, Uzair Khan, Connor Dietz, Elise Faure, Tarheen Fatima, Amanda MacPherson, Stephanie Mouchbahani-Constance, Daniel G. Bisson, Lisbet Haglund, Jean A. Ouellet, Laura S. Stone, Jonathan Samson, Mary-Jo Smith, Kjetil Ask, Alfredo Ribeiro-da-Silva, Rikard Blunck, Kate Poole, Emmanuel Bourinet, Reza Sharif-Naeini. TACAN Is an Ion Channel Involved in Sensing Mechanical Pain. Cell; DOI:https://doi.org/10.1016/j.cell.2020.01.033

Image: NCCIH