Emerging Roles for Ectonucleotidases in Pain-Sensing Neurons

Abstract

Nociceptive neurons located in the dorsal root ganglia detect painful stimuli and can be sensitized following inflammation or nerve injury. Many analgesics have ‘antinociceptive’ effects, which mean these drugs can reduce noxious thermal and mechanical sensitization—two symptoms that are associated with chronic pain. One drug that has been studied for its antinociceptive effects in rodents and humans is adenosine (Sawynok and Liu, 2003). Adenosine exerts its antinociceptive effects by activating the adenosine A1 receptor (A1R). A1R is expressed by nociceptive neurons and many other cells of the body, suggesting localized activation of this receptor in nociceptive neurons might inhibit pain without producing cardiovascular and other effects that are associated with systemic A1R activation. Recently, several new studies found that A1R can be activated locally near nociceptive neurons or their axons by ectonucleotidases—a class of enzymes that hydrolyze extracellular adenine nucleotides to adenosine. Moreover, this localized A1R activation was sufficient to inhibit chronic pain in animal models.