Purinergic signaling is involved in
pain generation and modulation in the nociceptive sensory nervous system.
Adenosine triphosphate (
ATP) induces
pain via activation of ionotropic P2X receptors while
adenosine mediates
analgesia via activation of metabotropic P1 receptors. These purinergic signaling are determined by ecto-
nucleotidases that control
ATP degradation and
adenosine generation. Using enzymatic histochemistry, we detected ecto-
AMPase activity in dental pulp, trigeminal ganglia (TG) neurons, and their nerve fibers. Using immunofluorescence staining, we confirmed the expression of
ecto-5'-nucleotidase (CD73) in trigeminal nociceptive neurons and their axonal fibers, including the nociceptive nerve fibers projecting into the brainstem. In addition, we detected the existence of CD73 and ecto-
AMPase activity in the nociceptive lamina of the trigeminal subnucleus caudalis (TSNC) in the brainstem. Furthermore, we demonstrated that incubation with specific anti-CD73 serum significantly reduced the ecto-
AMPase activity in the nociceptive lamina in the brainstem. Our results indicate that CD73 might participate in nociceptive modulation by affecting extracellular
adenosine generation in the trigeminal nociceptive pathway. Disruption of TG neuronal
ecto-nucleotidase expression and axonal terminal localization under certain circumstances such as chronic
inflammation,
oxidant stress, local constriction, and injury in trigeminal nerves may contribute to the pathogenesis of orofacial
neuropathic pain.