The role of carbon monoxide on the anti-nociceptive effects and expression of cannabinoid 2 receptors during painful diabetic neuropathy in mice
| Autor: | Mireia Carcolé, Sergi Leánez, Sílvia Castany, Olga Pol |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Agonist medicine.medical_specialty Indoles Metalloporphyrins medicine.drug_class medicine.medical_treatment Protoporphyrins Nitric Oxide Synthase Type I Pharmacology Heme oxygenases Diabetes Mellitus Experimental Receptor Cannabinoid CB2 Mice 03 medical and health sciences 0302 clinical medicine Diabetic Neuropathies Painful diabetic neuropathy Diabetes mellitus Organometallic Compounds medicine Animals Cannabinoid receptors Carbon monoxide Receptor Analgesics Carbon Monoxide business.industry Diabetes Nitric oxide synthases Antagonist Streptozotocin medicine.disease COPP Surgery Mice Inbred C57BL Heme oxygenase 030104 developmental biology Spinal Cord Hyperalgesia Enzyme Induction Cannabinoid Analgesia business Heme Oxygenase-1 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | PSYCHOPHARMACOLOGY r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname |
| ISSN: | 1432-2072 0033-3158 |
| DOI: | 10.1007/s00213-016-4271-4 |
| Popis: | The activation of cannabinoid 2 receptors (CB2R) attenuates chronic pain, but the role played by carbon monoxide synthesized by the inducible heme oxygenase 1 (HO-1) on the anti-nociceptive effects produced by a selective CB2R agonist, JWH-015, during painful diabetic neuropathy remains unknown. In streptozotocin (STZ)-induced diabetic mice, the anti-allodynic and anti-hyperalgesic effects of the subcutaneous administration of JWH-015 alone or combined with the intraperitoneal administration of a carbon monoxide-releasing molecule (tricarbonyldichlororuthenium(II) dimer (CORM-2)) or an HO-1 inducer compound (cobalt protoporphyrin IX (CoPP)) at 10 mg/kg were evaluated. Reversion of JWH-015 anti-nociceptive effects by the administration of an HO-1 inhibitor (tin protoporphyrin IX (SnPP)) and a CB2R antagonist (AM630) was also evaluated. Furthermore, the protein levels of HO-1, neuronal nitric oxide synthase (NOS1), and CB2R in diabetic mice treated with CORM-2 and CoPP alone or combined with JWH-015 were also assessed. The administration of JWH-015 dose dependently inhibited hypersensitivity induced by diabetes. The effects of JWH-015 were enhanced by their coadministration with CORM-2 or CoPP and reversed by SnPP or AM630. The increased protein levels of HO-1 induced by CORM-2 and CoPP treatments were further enhanced in JWH-015-treated mice. All treatments similarly enhanced the peripheral expression of CB2R and avoided the spinal cord over-expression of NOS1 induced by diabetes. The activation of HO-1 enhanced the anti-nociceptive effects of JWH-015 in diabetic mice, suggesting that coadministration of JWH-015 with CORM-2 or CoPP might be an interesting approach for the treatment of painful diabetic neuropathy in mice. |
| Databáze: | OpenAIRE |
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