|Ectonucleotidases are enzymes that convert ATP to adenosine. This spinal cord section was stained histochemically for ectonucleotidases. Intense staining is found in a region of the spinal cord where nociceptive neurons relay pain signals to the brain.|
More Americans suffer from chronic pain than heart disease, diabetes and cancer combined. Unfortunately, existing analgesics are not completely effective for all pain conditions and have serious side effects. A critical challenge for modern biomedical research is the need to provide pain relief without serious side effects. This project addresses this need by harnessing enzymes, called ectonucleotidases, that are found in nociceptive (pain-sensing) circuits in nervous system dorsal root ganglia (DRG) and in the spinal cord. Ectonucleotidases degrade purine nucleotides (like ATP and ADP) that cause pain into adenosine-a compound that has analgesic properties in rodents and humans. These studies are important in developing new proteins and small molecules that target ectonucleotidases for the treatment of acute and chronic pain, and have the potential to transform how we treat pain in millions of patients with fewer side effects.