New research indicates that the location of receptors that transmit pain signals is important in how big or small a pain signal will be and how effectively drugs can block those signals.
The researchers focused on a specific type of glutamate receptor that is part of the family of receptors called G-protein-coupled receptors, which are important in signaling between neurons.
Rats with nerve injuries displayed less spontaneous pain and less hypersensitivity to a painful stimulus when those nuclear receptors were blocked. But normal rats without nerve injuries had no changes in pain sensitivity when those receptors were blocked and the animals were exposed to a painful stimulus.
The researchers found that when these particular glutamate receptors on the nucleus of a nerve cell were activated, the response -- measured by the amount of calcium released-- was nine times larger than when the same type of receptor was activated on the cell's surface. Changes in calcium levels play a key role in signaling in neurons. Increased calcium can release important neurotransmitters, regulate specific genes and contribute to synaptic changes that are critical to pain signals.
They also found that the glutamate receptors on the nucleus responded to painful stimuli more robustly than the same types of receptors located on the cell's surface, and that when the cells encountered such a stimulus, some receptors migrated from the surface to the nucleus. The researchers also discovered that receptors located in the nucleus stopped activating pain signals when targeted with drugs.