Molecules 2012, 17(12), 13712-13726; doi:10.3390/molecules171213712
Article

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

Livio Luongo 1 email, Riccardo Petrelli 2 email, Luisa Gatta 1 email, Catia Giordano 1 email, Francesca Guida 1 email, Patrizia Vita 2 email, Palmarisa Franchetti 2 email, Mario Grifantini 2 email, Vito de Novellis 1 email, Loredana Cappellacci 2,* email and Sabatino Maione 1,* email
1 Section of Pharmacology “L. Donatelli”, Department of Experimental Medicine, Faculty of Medicine and Surgery, II University of Naples, via Costantinopoli 16, 80138 Naples, Italy 2 School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, Via S. Agostino 1, 62032 Camerino, Italy
* Authors to whom correspondence should be addressed.
Received: 12 October 2012; in revised form: 10 November 2012 / Accepted: 13 November 2012 / Published: 22 November 2012
(This article belongs to the Special Issue Nucleic Acid Analogs)
PDF Full-text Download PDF Full-Text [901 KB, Updated Version, uploaded 27 November 2012 16:21 CET]
The original version is still available [2232 KB, uploaded 22 November 2012 14:10 CET]
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.
Keywords: A1 adenosine receptor; neuropathic pain; allodynia; glia

Supplementary Files

Article Statistics

Click here to load and display the download statistics.

Cite This Article

MDPI and ACS Style

Luongo, L.; Petrelli, R.; Gatta, L.; Giordano, C.; Guida, F.; Vita, P.; Franchetti, P.; Grifantini, M.; Novellis, V.D.; Cappellacci, L.; Maione, S. 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. Molecules 2012, 17, 13712-13726.

AMA Style

Luongo L, Petrelli R, Gatta L, Giordano C, Guida F, Vita P, Franchetti P, Grifantini M, Novellis VD, Cappellacci L, Maione S. 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. Molecules. 2012; 17(12):13712-13726.

Chicago/Turabian Style

Luongo, Livio; Petrelli, Riccardo; Gatta, Luisa; Giordano, Catia; Guida, Francesca; Vita, Patrizia; Franchetti, Palmarisa; Grifantini, Mario; Novellis, Vito D.; Cappellacci, Loredana; Maione, Sabatino. 2012. "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." Molecules 17, no. 12: 13712-13726.

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert