PMID- 28530470 OWN - NLM STAT- MEDLINE DCOM- 20170808 LR - 20181113 IS - 1544-0591 (Electronic) IS - 0022-0345 (Print) IS - 0022-0345 (Linking) VI - 96 IP - 6 DP - 2017 Jun TI - CD73 Controls Extracellular Adenosine Generation in the Trigeminal Nociceptive Nerves. PG - 671-677 LID - 10.1177/0022034517692953 [doi] AB - 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. FAU - Liu, X AU - Liu X AD - 1 Department of Dentistry, Eastman Institute for Oral Health, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. AD - 2 Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. FAU - Ma, L AU - Ma L AD - 1 Department of Dentistry, Eastman Institute for Oral Health, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. AD - 3 Department of Dentistry, School of Stomatology, Zhengzhou University, Zhengzhou, China. FAU - Zhang, S AU - Zhang S AD - 1 Department of Dentistry, Eastman Institute for Oral Health, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. FAU - Ren, Y AU - Ren Y AD - 1 Department of Dentistry, Eastman Institute for Oral Health, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. FAU - Dirksen, R T AU - Dirksen RT AD - 2 Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. LA - eng GR - KL2 TR000095/TR/NCATS NIH HHS/United States GR - R01 AR059646/AR/NIAMS NIH HHS/United States PT - Journal Article DEP - 20170216 PL - United States TA - J Dent Res JT - Journal of dental research JID - 0354343 RN - EC 3.1.3.5 (5'-Nucleotidase) RN - EC 3.6.1.- (Adenosine Triphosphatases) SB - IM MH - 5'-Nucleotidase/*metabolism/*physiology MH - Adenosine Triphosphatases/*metabolism MH - Adolescent MH - Animals MH - Axons/*enzymology MH - Brain Stem/*enzymology MH - Dental Pulp/cytology/*enzymology MH - Facial Pain/enzymology MH - Fluorescent Antibody Technique MH - Humans MH - Hydrolysis MH - Molar, Third MH - Nerve Fibers/*enzymology MH - Signal Transduction MH - Staining and Labeling MH - Trigeminal Caudal Nucleus/*enzymology MH - Trigeminal Nerve/*enzymology MH - Young Adult PMC - PMC5444617 OTO - NOTNLM OT - antinociception OT - ecto-nucleotidases OT - neuropathic pain OT - orofacial pain OT - purinergic signaling OT - trigeminal nerves COIS- The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. EDAT- 2017/05/23 06:00 MHDA- 2017/08/09 06:00 PMCR- 2018/06/01 CRDT- 2017/05/23 06:00 PHST- 2017/05/23 06:00 [entrez] PHST- 2017/05/23 06:00 [pubmed] PHST- 2017/08/09 06:00 [medline] PHST- 2018/06/01 00:00 [pmc-release] AID - 10.1177_0022034517692953 [pii] AID - 10.1177/0022034517692953 [doi] PST - ppublish SO - J Dent Res. 2017 Jun;96(6):671-677. doi: 10.1177/0022034517692953. Epub 2017 Feb 16.