NIDCR Scientists Find Pain Receptor Enhancer

November 12, 2008

For anyone used to driving a car with an automatic transmission, a clutch can be a real revelation.  The same basic concept is true on the molecular level with the myriad protein receptors stitched into our cell membranes.  As classically described in biochemistry textbooks, each receptor binds its cognate incoming protein signal and, like punching the gas pedal, sets in motion the appropriate machinery within the cell to process the input.  But, as time and lots of hard work have shown, some receptors also employ helpers called signal enhancers.  These molecules, like a clutch pedal, modulate the force of the incoming signal, and they often do so from a position on the receptor that is nearby but not directly on the binding site. 

In the October 15 issue of the journal Bioorganic & Medicinal Chemistry, NIDCR scientists and their NIH colleagues report they have discovered an enhancer for the vanilloid receptor 1, or TRPV-1.  The authors explained that TRPV-1 resides on the plasma membrane of certain neurons, where various chemical stimuli can activate it to open a specific ion channel and ultimately transmit the unpleasant sensations of heat and pain to the brain.  The newly discovered enhancers are novel chemical derivatives of existing calcium channel blockers called 1,4-dihydropyridines, or DHP.  In their studies, the researchers found the DHP derivatives greatly increased the maximum flow of ions stimulated by capsaicin, the neuroactive component of chili peppers.  Interestingly, the derivatives had minimal or no agonistic, or inhibitory, activity of their own.  Commenting on their initial data, the authors stated that the enhancers open up the much needed therapeutic possibility of selectively regulating TRPV1 receptors in the nerve endings of skin and deep tissue and thus one day better controlling certain types of chronic pain.