Phosphodiesterase 2A Localized in the Spinal Cord Contributes to Inflammatory Pain Processing
| Autor: | Jana E. Lorenz, Gerd Geisslinger, Ruirui Lu, Dominique Thomas, Catherine Isabell Real, Domenico Del Turco, Nancy Lippold, Jessica Schlaudraff, Wiebke Kallenborn-Gerhardt, Aaron Bothe, Nerea Ferreirós, Achim Schmidtko |
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| Přispěvatelé: | Publica |
| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Phosphodiesterase Inhibitors Pain Real-Time Polymerase Chain Reaction Drug Hypersensitivity Mice chemistry.chemical_compound Internal medicine Spinal Cord Dorsal Horn Cyclic AMP medicine Animals Cyclic adenosine monophosphate Nucleotide Posterior Horn Cell Cyclic GMP Cyclic guanosine monophosphate Injections Spinal Pain Measurement Inflammation chemistry.chemical_classification Behavior Animal Triazines business.industry Imidazoles Zymosan Phosphodiesterase Anatomy Spinal cord Cyclic Nucleotide Phosphodiesterases Type 2 Immunohistochemistry Up-Regulation Mice Inbred C57BL Posterior Horn Cells Anesthesiology and Pain Medicine Endocrinology medicine.anatomical_structure Spinal Cord chemistry Neuropathic pain Neuralgia business Microdissection |
| Zdroj: | Anesthesiology. 121:372-382 |
| ISSN: | 0003-3022 |
| DOI: | 10.1097/aln.0000000000000270 |
| Popis: | Background: Phosphodiesterase 2A (PDE2A) is an evolutionarily conserved enzyme that catalyzes the degradation of the cyclic nucleotides, cyclic adenosine monophosphate, and/or cyclic guanosine monophosphate. Recent studies reported the expression of PDE2A in the dorsal horn of the spinal cord, pointing to a potential contribution to the processing of pain. However, the functions of PDE2A in spinal pain processing in vivo remained elusive. Methods: Immunohistochemistry, laser microdissection, and quantitative real-time reverse transcription polymerase chain reaction experiments were performed to characterize the localization and regulation of PDE2A protein and messenger RNA in the mouse spinal cord. Effects of the selective PDE2A inhibitor, BAY 60–7550 (Cayman Chemical, Ann Arbor, MI), in animal models of inflammatory pain (n = 6 to 10), neuropathic pain (n = 5 to 6), and after intrathecal injection of cyclic nucleotides (n = 6 to 8) were examined. Also, cyclic adenosine monophosphate and cyclic guanosine monophosphate levels in spinal cord tissues were measured by liquid chromatography tandem mass spectrometry. Results: The authors here demonstrate that PDE2A is distinctly expressed in neurons of the superficial dorsal horn of the spinal cord, and that its spinal expression is upregulated in response to hind paw inflammation. Administration of the selective PDE2A inhibitor, BAY 60–7550, increased the nociceptive behavior of mice in animal models of inflammatory pain. Moreover, BAY 60–7550 increased the pain hypersensitivity induced by intrathecal delivery of cyclic adenosine monophosphate, but not of cyclic guanosine monophosphate, and it increased the cyclic adenosine monophosphate levels in spinal cord tissues. Conclusion: Our findings indicate that PDE2A contributes to the processing of inflammatory pain in the spinal cord. |
| Databáze: | OpenAIRE |
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