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- Title
5'-Chloro-5'-deoxy-(±)-ENBA, a Potent and Selective Adenosine A<sub>1 </sub>Receptor Agonist, Alleviates Neuropathic Pain in Mice Through Functional Glial and Microglial Changes without Affecting Motor or Cardiovascular Functions.
- Authors
Luongo, Livio; Petrelli, Riccardo; Gatta, Luisa; Giordano, Catia; Guida, Francesca; Vita, Patrizia; Franchetti, Palmarisa; Grifantini, Mario; de Novellis, Vito; Cappellacci, Loredana; Maione, Sabatino
- Abstract
This study was undertaken in order to investigate the effect of chronic treatment with 5'-chloro-5'-deoxy-(±)-ENBA, a potent and highly selective agonist of human adenosine A1 receptor, on thermal hyperalgesia and mechanical allodynia in a mouse model of neuropathic pain, the Spared Nerve Injury (SNI) of the sciatic nerve. Chronic systemic administration of 5'-chloro-5'-deoxy-(±)-ENBA (0.5 mg/kg, i.p.) reduced both mechanical allodynia and thermal hyperalgesia 3 and 7 days post-SNI, in a way prevented by DPCPX (3 mg/kg, i.p.), a selective A1 adenosine receptor antagonist, without exerting any significant change on the motor coordination or arterial blood pressure. In addition, a single intraperitoneal injection of 5'-chloro-5'-deoxy-(±)-ENBA (0.5 mg/kg, i.p.) 7 days post-SNI also reduced both symptoms for at least two hours. SNI was associated with spinal changes in microglial activation ipsilaterally to the nerve injury. Activated, hypertrophic microglia were significantly reduced by 5'-chloro-5'-deoxy-(±)-ENBA chronic treatment. Our results demonstrated an involvement of adenosine A1 receptor in the amplified nociceptive thresholds and in spinal glial and microglial changes occurred in neuropathic pain, without affecting motor coordination or blood pressure. Our data suggest a possible use of adenosine A1 receptor agonist in neuropathic pain symptoms.
- Subjects
PAIN management; ADENOSINES; SCIATIC nerve diseases; ANIMAL models in research; PAIN; NEUROGLIA; MOTOR ability; CARDIOVASCULAR system
- Publication
Molecules, 2012, Vol 17, Issue 12, p13712
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules171213712