Since launching her own lab at Yale in 2018, Candie Paulsen and her research team have been working to crack a longstanding mystery: How are pain signals regulated in the human body? And why do they sometimes go haywire?
While researchers had long known that calcium plays a key role in alerting the body to pain, they didn't understand how the response turns off or why the interaction sometimes goes awry, leading to chronic pain and inflammation.
For years they'd focused on TRPA1, a protein channel in nerve cells that lets calcium flow in, allowing the body to sense pain and trigger inflammation. Too much calcium can damage cells. Somewhere along the TRPA1 channel, researchers deduced, was a mechanism that shut down the calcium flow - and the resulting pain signals - but no one could pin it down.
"We finally found it," said Paulsen, an assistant professor of Molecular Biophysics and Biochemistry at the Wu Tsai Institute at Yale who led an all-Yale research team at her Science Hill lab. The hidden culprit, they report in a new study in Nature Communications, is a protein called calmodulin, which Paulsen's team discovered plays a key role in turning off the TRPA1 channel after calcium has passed through it.
How? By latching onto a docking site at the far end of the channel. This latching is essential for shutting down the activated channel before it becomes overactive, which can fuel pain and inflammation.
The findings, Paulsen said, may lead to better interventions in pain management.
