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Effect of Medetomidine, Dexmedetomidine, and Their Reversal with Atipamezole on the Nociceptive Withdrawal Reflex in Beagles
SIMPLE SUMMARY: Medetomidine, an alpha-2 agonist routinely used to provide sedation and pain relief in dogs, is a mixture of dexmedetomidine and levomedetomidine in equal proportions. Dexmedetomidine, considered to be the only active component in the mixture, is also marketed alone. Sedation caused...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401557/ https://www.ncbi.nlm.nih.gov/pubmed/32708294 http://dx.doi.org/10.3390/ani10071240 |
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author | Siegenthaler, Joëlle Pleyers, Tekla Raillard, Mathieu Spadavecchia, Claudia Levionnois, Olivier Louis |
author_facet | Siegenthaler, Joëlle Pleyers, Tekla Raillard, Mathieu Spadavecchia, Claudia Levionnois, Olivier Louis |
author_sort | Siegenthaler, Joëlle |
collection | PubMed |
description | SIMPLE SUMMARY: Medetomidine, an alpha-2 agonist routinely used to provide sedation and pain relief in dogs, is a mixture of dexmedetomidine and levomedetomidine in equal proportions. Dexmedetomidine, considered to be the only active component in the mixture, is also marketed alone. Sedation caused by both formulations can be reversed using atipamezole, which shortens recovery. Dexmedetomidine provides analgesic effects similar to medetomidine, but it remains unclear at which dose and whether the analgesic effects of medetomidine or dexmedetomidine disappear once atipamezole is injected. The present trial aimed at elucidating these uncertainties using the nociceptive withdrawal reflex model. This model allows for quantification of analgesia by measuring specific activity from muscles involved in limb withdrawal in response to mild electrical stimulation. In eight beagles, the model was applied to compare the extent of pain relief provided by medetomidine and dexmedetomidine and to investigate whether complete reversal occurs after the administration of atipamezole. No difference in analgesic efficacy was identified between the two formulations. Both sedation and pain relief terminated rapidly when atipamezole was administered. These findings indicate that medetomidine and dexmedetomidine provide comparable levels of pain relief and that additional analgesics may be necessary when atipamezole is administered to dogs experiencing pain. ABSTRACT: The objectives were: (1) to compare the antinociceptive activity of dexmedetomidine and medetomidine, and (2) to investigate its modulation by atipamezole. This prospective, randomized, blinded experimental trial was carried out on eight beagles. During the first session, dogs received either medetomidine (MED) (0.02 mg kg(−1) intravenously (IV)] or dexmedetomidine (DEX) [0.01 mg kg(−1) IV), followed by either atipamezole (ATI) (0.1 mg kg(−1)) or an equivalent volume of saline (SAL) administered intramuscularly 45 min later. The opposite treatments were administered in a second session 10–14 days later. The nociceptive withdrawal reflex (NWR) threshold was determined using a continuous tracking approach. Sedation was scored (0 to 21) every 10 min. Both drugs (MED and DEX) increased the NWR thresholds significantly up to 5.0 (3.7–5.9) and 4.4 (3.9–4.8) times the baseline (p = 0.547), at seven (3–11) and six (4–9) minutes (p = 0.938), respectively. Sedation scores were not different between MED and DEX during the first 45 min (15 (12–17), p = 0.67). Atipamezole antagonized sedation within 25 (15–25) minutes (p = 0.008) and antinociception within five (3–6) minutes (p = 0.008). Following atipamezole, additional analgesics may be needed to maintain pain relief. |
format | Online Article Text |
id | pubmed-7401557 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74015572020-08-07 Effect of Medetomidine, Dexmedetomidine, and Their Reversal with Atipamezole on the Nociceptive Withdrawal Reflex in Beagles Siegenthaler, Joëlle Pleyers, Tekla Raillard, Mathieu Spadavecchia, Claudia Levionnois, Olivier Louis Animals (Basel) Article SIMPLE SUMMARY: Medetomidine, an alpha-2 agonist routinely used to provide sedation and pain relief in dogs, is a mixture of dexmedetomidine and levomedetomidine in equal proportions. Dexmedetomidine, considered to be the only active component in the mixture, is also marketed alone. Sedation caused by both formulations can be reversed using atipamezole, which shortens recovery. Dexmedetomidine provides analgesic effects similar to medetomidine, but it remains unclear at which dose and whether the analgesic effects of medetomidine or dexmedetomidine disappear once atipamezole is injected. The present trial aimed at elucidating these uncertainties using the nociceptive withdrawal reflex model. This model allows for quantification of analgesia by measuring specific activity from muscles involved in limb withdrawal in response to mild electrical stimulation. In eight beagles, the model was applied to compare the extent of pain relief provided by medetomidine and dexmedetomidine and to investigate whether complete reversal occurs after the administration of atipamezole. No difference in analgesic efficacy was identified between the two formulations. Both sedation and pain relief terminated rapidly when atipamezole was administered. These findings indicate that medetomidine and dexmedetomidine provide comparable levels of pain relief and that additional analgesics may be necessary when atipamezole is administered to dogs experiencing pain. ABSTRACT: The objectives were: (1) to compare the antinociceptive activity of dexmedetomidine and medetomidine, and (2) to investigate its modulation by atipamezole. This prospective, randomized, blinded experimental trial was carried out on eight beagles. During the first session, dogs received either medetomidine (MED) (0.02 mg kg(−1) intravenously (IV)] or dexmedetomidine (DEX) [0.01 mg kg(−1) IV), followed by either atipamezole (ATI) (0.1 mg kg(−1)) or an equivalent volume of saline (SAL) administered intramuscularly 45 min later. The opposite treatments were administered in a second session 10–14 days later. The nociceptive withdrawal reflex (NWR) threshold was determined using a continuous tracking approach. Sedation was scored (0 to 21) every 10 min. Both drugs (MED and DEX) increased the NWR thresholds significantly up to 5.0 (3.7–5.9) and 4.4 (3.9–4.8) times the baseline (p = 0.547), at seven (3–11) and six (4–9) minutes (p = 0.938), respectively. Sedation scores were not different between MED and DEX during the first 45 min (15 (12–17), p = 0.67). Atipamezole antagonized sedation within 25 (15–25) minutes (p = 0.008) and antinociception within five (3–6) minutes (p = 0.008). Following atipamezole, additional analgesics may be needed to maintain pain relief. MDPI 2020-07-21 /pmc/articles/PMC7401557/ /pubmed/32708294 http://dx.doi.org/10.3390/ani10071240 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Siegenthaler, Joëlle Pleyers, Tekla Raillard, Mathieu Spadavecchia, Claudia Levionnois, Olivier Louis Effect of Medetomidine, Dexmedetomidine, and Their Reversal with Atipamezole on the Nociceptive Withdrawal Reflex in Beagles |
title | Effect of Medetomidine, Dexmedetomidine, and Their Reversal with Atipamezole on the Nociceptive Withdrawal Reflex in Beagles |
title_full | Effect of Medetomidine, Dexmedetomidine, and Their Reversal with Atipamezole on the Nociceptive Withdrawal Reflex in Beagles |
title_fullStr | Effect of Medetomidine, Dexmedetomidine, and Their Reversal with Atipamezole on the Nociceptive Withdrawal Reflex in Beagles |
title_full_unstemmed | Effect of Medetomidine, Dexmedetomidine, and Their Reversal with Atipamezole on the Nociceptive Withdrawal Reflex in Beagles |
title_short | Effect of Medetomidine, Dexmedetomidine, and Their Reversal with Atipamezole on the Nociceptive Withdrawal Reflex in Beagles |
title_sort | effect of medetomidine, dexmedetomidine, and their reversal with atipamezole on the nociceptive withdrawal reflex in beagles |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401557/ https://www.ncbi.nlm.nih.gov/pubmed/32708294 http://dx.doi.org/10.3390/ani10071240 |
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