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5'-Chloro-5'-deoxy-(±)-ENBA, a Potent and Selective Adenosine A1 Receptor Agonist, Alleviates Neuropathic Pain in Mice Through Functional Glial and Microglial Changes without Affecting Motor or Cardiovascular Functions

5'-Chloro-5'-deoxy-(±)-ENBA, a Potent and Selective Adenosine A1 Receptor Agonist, Alleviates Neuropathic Pain in Mice Through Functional Glial and Microglial Changes without Affecting Motor or Cardiovascular Functions

Authors :
Palmarisa Franchetti
Vito de Novellis
Loredana Cappellacci
Patrizia Vita
Riccardo Petrelli
Catia Giordano
Francesca Guida
L. Luongo
Sabatino Maione
Mario Grifantini
Luisa Gatta
Luongo, L.
Petrelli, R.
Gatta, L.
Giordano, C.
Guida, F.
Vita, P.
Franchetti, P.
Grifantini, M.
De Novellis, V.
Cappellacci, L.
Maione, S.
Source :
Molecules; Volume 17; Issue 12; Pages: 13712-13726, Molecules
Publication Year :
2012
Publisher :
MDPI AG, 2012.

Abstract

This study was undertaken in order to investigate the effect of chronic treatment with 5#8242;-chloro-5#8242;-deoxy-(#177;)-ENBA, a potent and highly selective agonist of human adenosine A(1) 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#8242;-chloro-5#8242;-deoxy-(#177;)-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 A(1) adenosine receptor antagonist, without exerting any significant change on the motor coordination or arterial blood pressure. In addition, a single intraperitoneal injection of 5#8242;-chloro-5#8242;-deoxy-(#177;)-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#8242;-chloro-5#8242;-deoxy-(#177;)-ENBA chronic treatment. Our results demonstrated an involvement of adenosine A(1) 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 A(1) receptor agonist in neuropathic pain symptoms.

Details

ISSN :
14203049
Volume :
17
Database :
OpenAIRE
Journal :
Molecules
Accession number :
edsair.doi.dedup.....e2df52c056da9e23aa05dc773280ead5
Full Text :
https://doi.org/10.3390/molecules171213712