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Vortioxetine as an analgesic in preclinical inflammatory pain models: Mechanism of action

Authorized Users Only
2021
Authors
Todorović, Marija
Micov, Ana
Nastić, Katarina
Tomić, Maja
Pecikoza, Uroš
Vuković, Milja
Stepanović-Petrović, Radica
Article (Published version)
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Abstract
Vortioxetine is a novel atypical antidepressant with multimodal activity that has recently demonstrated efficacy against neuropathic pain. There is no published data about its analgesic properties in models characterized by peripheral inflammation and consequent pain pathway sensitization, nor data on its mechanism of antinociceptive action. This study aimed to investigate vortioxetine's antinociceptive/antihyperalgesic effects in trigeminal, visceral, and somatic inflammatory pain models, and provide evidence on its mechanism of action in the modulation of trigeminal nociception. Vortioxetine's effects on the nociceptive behavior in orofacial formalin test (OFT) and acetic acid-writhing test in mice and on mechanical hyperalgesia in carrageenan-induced paw inflammation in rats were examined following peroral single administration. The involvement of serotonergic/adrenergic/cholinergic/cannabinoid/adenosine receptors was evaluated in OFT by intraperitoneally treating mice with an appro...priate antagonist immediately after vortioxetine application. We used antagonists of 5-HT1B/1D serotonergic (GR 127935), α1-adrenergic (prazosin), α2-adrenergic (yohimbine), β1-adrenergic (metoprolol), muscarinic (atropine), α7 nicotinic (methyllycaconitine), CB1/CB2 cannabinoid (AM251 and AM630), and adenosine A1 (DPCPX) receptors. Vortioxetine dose-dependently reduced pain behavior in OFT and acetic acid writhing test, as well as inflammatory hyperalgesia in paw pressure test. All examined antagonists except prazosin dose-dependently inhibited vortioxetine's antinociceptive effects. In conclusion, vortioxetine exerted analgesic efficacy in trigeminal, visceral, and somatic inflammatory pain. The effect is at least in part mediated by 5-HT1B/1D serotonergic, α2/β1-adrenergic, muscarinic and nicotinic cholinergic, CB1/CB2 cannabinoid, and adenosine A1 receptors. These findings contribute to better understanding of the analgesic effect of vortioxetine and suggest its potential usefulness for inflammatory pain treatment.

Keywords:
Pain-modulating receptors / somatic pain / trigeminal pain / visceral pain / vortioxetine
Source:
Fundamental and Clinical Pharmacology, 2021, 36, 2, 237-249
Publisher:
  • John Wiley and Sons Inc
Funding / projects:
  • Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200161 (University of Belgrade, Faculty of Pharmacy) (RS-200161)

DOI: 10.1111/fcp.12737

ISSN: 0767-3981

WoS: 000728693700001

Scopus: 2-s2.0-85120799868
[ Google Scholar ]
2
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/4009
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Todorović, Marija
AU  - Micov, Ana
AU  - Nastić, Katarina
AU  - Tomić, Maja
AU  - Pecikoza, Uroš
AU  - Vuković, Milja
AU  - Stepanović-Petrović, Radica
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4009
AB  - Vortioxetine is a novel atypical antidepressant with multimodal activity that has recently demonstrated efficacy against neuropathic pain. There is no published data about its analgesic properties in models characterized by peripheral inflammation and consequent pain pathway sensitization, nor data on its mechanism of antinociceptive action. This study aimed to investigate vortioxetine's antinociceptive/antihyperalgesic effects in trigeminal, visceral, and somatic inflammatory pain models, and provide evidence on its mechanism of action in the modulation of trigeminal nociception. Vortioxetine's effects on the nociceptive behavior in orofacial formalin test (OFT) and acetic acid-writhing test in mice and on mechanical hyperalgesia in carrageenan-induced paw inflammation in rats were examined following peroral single administration. The involvement of serotonergic/adrenergic/cholinergic/cannabinoid/adenosine receptors was evaluated in OFT by intraperitoneally treating mice with an appropriate antagonist immediately after vortioxetine application. We used antagonists of 5-HT1B/1D serotonergic (GR 127935), α1-adrenergic (prazosin), α2-adrenergic (yohimbine), β1-adrenergic (metoprolol), muscarinic (atropine), α7 nicotinic (methyllycaconitine), CB1/CB2 cannabinoid (AM251 and AM630), and adenosine A1 (DPCPX) receptors. Vortioxetine dose-dependently reduced pain behavior in OFT and acetic acid writhing test, as well as inflammatory hyperalgesia in paw pressure test. All examined antagonists except prazosin dose-dependently inhibited vortioxetine's antinociceptive effects. In conclusion, vortioxetine exerted analgesic efficacy in trigeminal, visceral, and somatic inflammatory pain. The effect is at least in part mediated by 5-HT1B/1D serotonergic, α2/β1-adrenergic, muscarinic and nicotinic cholinergic, CB1/CB2 cannabinoid, and adenosine A1 receptors. These findings contribute to better understanding of the analgesic effect of vortioxetine and suggest its potential usefulness for inflammatory pain treatment.
PB  - John Wiley and Sons Inc
T2  - Fundamental and Clinical Pharmacology
T1  - Vortioxetine as an analgesic in preclinical inflammatory pain models: Mechanism of action
VL  - 36
IS  - 2
SP  - 237
EP  - 249
DO  - 10.1111/fcp.12737
ER  - 
@article{
author = "Todorović, Marija and Micov, Ana and Nastić, Katarina and Tomić, Maja and Pecikoza, Uroš and Vuković, Milja and Stepanović-Petrović, Radica",
year = "2021",
abstract = "Vortioxetine is a novel atypical antidepressant with multimodal activity that has recently demonstrated efficacy against neuropathic pain. There is no published data about its analgesic properties in models characterized by peripheral inflammation and consequent pain pathway sensitization, nor data on its mechanism of antinociceptive action. This study aimed to investigate vortioxetine's antinociceptive/antihyperalgesic effects in trigeminal, visceral, and somatic inflammatory pain models, and provide evidence on its mechanism of action in the modulation of trigeminal nociception. Vortioxetine's effects on the nociceptive behavior in orofacial formalin test (OFT) and acetic acid-writhing test in mice and on mechanical hyperalgesia in carrageenan-induced paw inflammation in rats were examined following peroral single administration. The involvement of serotonergic/adrenergic/cholinergic/cannabinoid/adenosine receptors was evaluated in OFT by intraperitoneally treating mice with an appropriate antagonist immediately after vortioxetine application. We used antagonists of 5-HT1B/1D serotonergic (GR 127935), α1-adrenergic (prazosin), α2-adrenergic (yohimbine), β1-adrenergic (metoprolol), muscarinic (atropine), α7 nicotinic (methyllycaconitine), CB1/CB2 cannabinoid (AM251 and AM630), and adenosine A1 (DPCPX) receptors. Vortioxetine dose-dependently reduced pain behavior in OFT and acetic acid writhing test, as well as inflammatory hyperalgesia in paw pressure test. All examined antagonists except prazosin dose-dependently inhibited vortioxetine's antinociceptive effects. In conclusion, vortioxetine exerted analgesic efficacy in trigeminal, visceral, and somatic inflammatory pain. The effect is at least in part mediated by 5-HT1B/1D serotonergic, α2/β1-adrenergic, muscarinic and nicotinic cholinergic, CB1/CB2 cannabinoid, and adenosine A1 receptors. These findings contribute to better understanding of the analgesic effect of vortioxetine and suggest its potential usefulness for inflammatory pain treatment.",
publisher = "John Wiley and Sons Inc",
journal = "Fundamental and Clinical Pharmacology",
title = "Vortioxetine as an analgesic in preclinical inflammatory pain models: Mechanism of action",
volume = "36",
number = "2",
pages = "237-249",
doi = "10.1111/fcp.12737"
}
Todorović, M., Micov, A., Nastić, K., Tomić, M., Pecikoza, U., Vuković, M.,& Stepanović-Petrović, R.. (2021). Vortioxetine as an analgesic in preclinical inflammatory pain models: Mechanism of action. in Fundamental and Clinical Pharmacology
John Wiley and Sons Inc., 36(2), 237-249.
https://doi.org/10.1111/fcp.12737
Todorović M, Micov A, Nastić K, Tomić M, Pecikoza U, Vuković M, Stepanović-Petrović R. Vortioxetine as an analgesic in preclinical inflammatory pain models: Mechanism of action. in Fundamental and Clinical Pharmacology. 2021;36(2):237-249.
doi:10.1111/fcp.12737 .
Todorović, Marija, Micov, Ana, Nastić, Katarina, Tomić, Maja, Pecikoza, Uroš, Vuković, Milja, Stepanović-Petrović, Radica, "Vortioxetine as an analgesic in preclinical inflammatory pain models: Mechanism of action" in Fundamental and Clinical Pharmacology, 36, no. 2 (2021):237-249,
https://doi.org/10.1111/fcp.12737 . .

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