Back to Journals » Journal of Pain Research » Volume 14

Antinociceptive Effect of Lodenafil Carbonate in Rodent Models of Inflammatory Pain and Spinal Nerve Ligation-Induced Neuropathic Pain

Authors Vieira M C, Monte FBM, Dematte BE, Montagnoli TL, Montes GC, da Silva JS, Mendez-Otero R, Trachez MM, Sudo RT, Zapata-Sudo G

Received 11 December 2020

Accepted for publication 16 February 2021

Published 30 March 2021 Volume 2021:14 Pages 857—866


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Professor E. Alfonso Romero-Sandoval

Marcio Carneiro Vieira,1,2 Fernanda Bezerra de Mello Monte,3 Bruno Eduardo Dematte,3 Tadeu Lima Montagnoli,3 Guilherme Carneiro Montes,3 Jaqueline Soares da Silva,3 Rosalia Mendez-Otero,4 Margarete Manhães Trachez,3 Roberto Takashi Sudo,1,3 Gisele Zapata-Sudo1,3

1Programa de Pós-graduação em Ciências Cirúrgicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil; 2Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil; 3Programa de Pesquisa em Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil; 4Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio De Janeiro, 21941-902, Brazil

Correspondence: Gisele Zapata-Sudo
Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil
Tel +55 21 3938 6505
Email [email protected]

Introduction: New therapeutic alternatives for pain relief include the use of phosphodiesterase-5 (PDE5) inhibitors, which could prevent the transmission of painful stimuli by neuron hyperpolarization via nitric oxide (NO)/cyclic 3ʹ,5ʹ-guanosine monophosphate (cGMP) pathway. The present work investigated the antinociceptive activity of a new PDE5 inhibitor, lodenafil carbonate, in inflammatory and neuropathic pain models.
Methods and Results: Although no effect was detected on neurogenic phase of formalin test in mice, oral administration of lodenafil carbonate dose-dependently reduced reactivity in the inflammatory phase (200.6 ± 39.1 to 81.9 ± 18.8 s at 10 μmol/kg, p= 0.0172) and this effect was totally blocked by NO synthase inhibitor, L-Nω-nitroarginine methyl ester (L-NAME). Lodenafil carbonate (10 μmol/kg p.o.) significantly reduced nociceptive response as demonstrated by increased paw withdrawal latency to thermal stimulus (from 6.8 ± 0.7 to 10.6 ± 1.3 s, p= 0.0006) and paw withdrawal threshold to compressive force (from 188.0 ± 14.0 to 252.5 ± 5.3 g, p< 0.0001) in carrageenan-induced paw inflammation model. In a spinal nerve ligation-induced neuropathic pain, oral lodenafil carbonate (10 μmol/kg) also reversed thermal hyperalgesia and mechanical allodynia by increasing paw withdrawal latency from 17.9 ± 1.5 to 22.8 ± 1.9 s (p= 0.0062) and paw withdrawal threshold from 26.0 ± 2.8 to 41.4 ± 2.9 g (p= 0.0196). These effects were reinforced by the reduced GFAP (3.4 ± 0.5 to 1.4 ± 0.3%, p= 0.0253) and TNF-alpha (1.1 ± 0.1 to 0.4 ± 0.1%, p= 0.0111) stained area densities as detected by immunofluorescence in ipsilateral dorsal horns.
Conclusion: Lodenafil carbonate demonstrates important analgesic activity by promoting presynaptic hyperpolarization and preventing neuroplastic changes, which may perpetuate chronic pain, thus representing a potential treatment for neuropathic pain.

Keywords: neuropathic pain, inflammatory pain, phosphodiesterase 5 inhibitor, lodenafil carbonate, spinal cord, GFAP

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]