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Volume 11
Issue 12
10.3390/biomedicines11123249
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Article

Antinociceptive Effect of the Combination of a Novel α4β2* Agonist with Donepezil in a Chronic Pain Model

by
Fernanda B. de M. Monte
1,
Tadeu L. Montagnoli
1,
Bruno E. Dematté
2,
Fernanda Gubert
3,
Vitória S. Ventura
4,
Jaqueline S. da Silva
1,2,
Margarete M. Trachez
4,
Rosalia Mendez-Otero
5 and
Gisele Zapata-Sudo
1,2,3,4,*
1
Programa de Pós-Graduação em Farmacologia e Química Medicinal, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-617, Brazil
2
Programa de Pós-Graduação em Cardiologia, Instituto do Coração Edson Saad, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-617, Brazil
3
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-617, Brazil
4
Instituto do Coração Edson Saad, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-617, Brazil
5
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-617, Brazil
*
Author to whom correspondence should be addressed.
Biomedicines 2023, 11(12), 3249; https://doi.org/10.3390/biomedicines11123249
Submission received: 1 October 2023 / Revised: 27 November 2023 / Accepted: 30 November 2023 / Published: 8 December 2023
(This article belongs to the Special Issue Molecular Mechanisms of Chronic Pain and New Therapeutic Strategies Volume II)
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Abstract

Chronic pain presents a major challenge in contemporary medicine, given the limited effectiveness and numerous adverse effects linked to available treatments. Recognizing the potential of the cholinergic pathway as a therapeutic target, the present work evaluates the antinociceptive activity of a combination of Cris-104, a novel α4β2* receptor agonist, and donepezil, a central anticholinesterase agent. Isobolographic analysis revealed that equimolar combination was approximately 10 times more potent than theoretically calculated equipotent additive dose. Administration of Cris-104 and donepezil combination (3 μmol/kg) successfully reversed hyperalgesia and mechanical allodynia observed in rats subjected to spinal nerve ligation (SNL). The combination also modulated neuroinflammation by reducing astrocyte activation, evident in the decreased expression of glial fibrillary acidic protein (GFAP) in the spinal cord. The observed synergism in combining a nicotinic receptor agonist with an anticholinesterase agent underscores its potential for treating chronic pain. This alternative therapeutic distinct advantage, including dose reduction and high selectivity for the receptor, contribute to a more favorable profile with minimized adverse effects.
Keywords: chronic pain; spinal nerve ligation; nicotinic receptor; anticholinesterase; neuroinflammation chronic pain; spinal nerve ligation; nicotinic receptor; anticholinesterase; neuroinflammation

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MDPI and ACS Style

Monte, F.B.d.M.; Montagnoli, T.L.; Dematté, B.E.; Gubert, F.; Ventura, V.S.; da Silva, J.S.; Trachez, M.M.; Mendez-Otero, R.; Zapata-Sudo, G. Antinociceptive Effect of the Combination of a Novel α4β2* Agonist with Donepezil in a Chronic Pain Model. Biomedicines 2023, 11, 3249. https://doi.org/10.3390/biomedicines11123249

AMA Style

Monte FBdM, Montagnoli TL, Dematté BE, Gubert F, Ventura VS, da Silva JS, Trachez MM, Mendez-Otero R, Zapata-Sudo G. Antinociceptive Effect of the Combination of a Novel α4β2* Agonist with Donepezil in a Chronic Pain Model. Biomedicines. 2023; 11(12):3249. https://doi.org/10.3390/biomedicines11123249

Chicago/Turabian Style

Monte, Fernanda B. de M., Tadeu L. Montagnoli, Bruno E. Dematté, Fernanda Gubert, Vitória S. Ventura, Jaqueline S. da Silva, Margarete M. Trachez, Rosalia Mendez-Otero, and Gisele Zapata-Sudo. 2023. "Antinociceptive Effect of the Combination of a Novel α4β2* Agonist with Donepezil in a Chronic Pain Model" Biomedicines 11, no. 12: 3249. https://doi.org/10.3390/biomedicines11123249

APA Style

Monte, F. B. d. M., Montagnoli, T. L., Dematté, B. E., Gubert, F., Ventura, V. S., da Silva, J. S., Trachez, M. M., Mendez-Otero, R., & Zapata-Sudo, G. (2023). Antinociceptive Effect of the Combination of a Novel α4β2* Agonist with Donepezil in a Chronic Pain Model. Biomedicines, 11(12), 3249. https://doi.org/10.3390/biomedicines11123249

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