July 19 (UPI) -- A recent study by Thomas Jefferson University identified phosphorylation outside of a cell as a potential new way to target chronic and pathologic pain.
Phosphorylation is a common type of protein modification that can occur outside of the neuron and impacts protein function and pathological pain. But researchers show in a study published July 18 in PLOS Biology how they discovered phosphorylation functions in a new way to change the location of proteins that are vital for neuronal function and pathological pain.
Pathologic pain differs from pain from inflammation or impact in that it comes from neuronal dysfunction, which results in pain being felt even when there is no underlying cause or pain that continues long after an initiating event.
"Although we have yet to discover the exact mechanism that causes this modification," Matthew Dalva, professor and vice chair in the Department of Neuroscience in The Vickie and Jack Farber Institute for Neuroscience at Sidney Kimmel Medical College, Thomas Jefferson University, said in a press release. "This finding offers both a target for developing new treatments and a strong new tool for studying synapses in general."
NMDA receptors on neurons plays an important role in pathologic pain as well as other neurological processes like memory and learning, so targeting the receptors is not ideal.
The research team, in collaboration with New York University and the University of Texas at Dallas, showed that in response to pain, a second receptor known as the ephrin B receptor, or EphB2, is phosphorylated outside the neuron.
The process allows the EphB2 attaches to the NMDA receptor, moving the NMDA receptor into the synaptic space and modifies its function, which leads to increased pain sensitivity. The researchers found that chemicals that block this interaction between EphB2 and NMDA also block pain.
"Because the protein modification that initiates nerve sensitivity to pain occurs outside of the cell, it offers us an easier target for drug development," Dalva said. "This is a promising advance in the field of pain management."
