TNAP and pain control

Abstract

Chronic pain is one of the most debilitating and expensive diseases, yet current therapies are often insufficient in bringing about long-term relief. Further, many treatments for chronic pain also carry significant side effects. The molecule adenosine has long been identified as a potent inhibitor of nociceptive circuits in the spinal cord; however, the widespread expression of adenosine receptors in many organ systems has limited its use as an analgesic. Recently several 5' ectonucleotidases, including tissue non-specific alkaline phosphatase (TNAP), have been characterized for their ability to generate endogenous adenosine in nociceptive circuitry of the dorsal spinal cord. These ectonucleotidases have the ability to hydrolyze the endogenous pronociceptive nucleotides like adenosine triphosphate (ATP) into the antinociceptive nucleoside adenosine. This chapter discusses the role of TNAP and other ectonucleotidases in nociceptive circuits, and their potential as future targets of new therapeutics to treat chronic pain.