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A Comparison of the Antinociceptive Properties of SJP-005 and Morphine in Rats

SJP-005 (a combination of ketotifen and ibuprofen) is being developed as a potential treatment for pain and for opioid use disorder. It is therefore important to investigate the potential antinociceptive properties of SJP-005. Two studies were conducted to evaluate the potential effects of SJP-005 i...

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Autores principales: Verster, Joris C, Scholey, Andrew, Dahl, Thomas A, Iversen, Jacqueline M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916340/
https://www.ncbi.nlm.nih.gov/pubmed/33578710
http://dx.doi.org/10.3390/pharmaceutics13020243
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author Verster, Joris C
Scholey, Andrew
Dahl, Thomas A
Iversen, Jacqueline M
author_facet Verster, Joris C
Scholey, Andrew
Dahl, Thomas A
Iversen, Jacqueline M
author_sort Verster, Joris C
collection PubMed
description SJP-005 (a combination of ketotifen and ibuprofen) is being developed as a potential treatment for pain and for opioid use disorder. It is therefore important to investigate the potential antinociceptive properties of SJP-005. Two studies were conducted to evaluate the potential effects of SJP-005 in rats. Study 1 applied the von Frey test to examine the antinociceptive effect of morphine with and without SJP-005 in adjuvant-induced hypersensitivity to tactile stimulation. In a double-blind, between-groups design, groups of rats (n = 10 each) received morphine at 3, 10, or 30 mg/kg bodyweight (bw) (subcutaneous injection) with or without SJP-005 (oral). Mechanic allodynia and paw volume were assessed before and after treatment. Study 2 utilized the hot plate test. Using a crossover design, groups of rats (n = 10 each) received either morphine at 3, 10, or 30 mg/kg bw (subcutaneous injection) preceded by oral administration of placebo (Week 1) or SJP-005 (Week 2). In Study 1, in the von Frey up-and-down test, Δ paw withdrawal responses in Group 1 (3 mg/kg bw morphine) were significantly lower compared to those in Group 4 (3 mg/kg bw morphine plus SJP-005), whereas the differences in Δ paw withdrawal between Group 2 and Group 5 (10 mg/kg bw morphine with and without SJP-005) and between Group 3 and Group 6 (10 mg/kg bw morphine with and without SJP-005) did not reach statistical difference. Trendline analysis of the dose–response relationship for the morphine + placebo groups and morphine + SJP-005 groups revealed no significant differences in the intercepts and slopes. In Study 2, no significant differences were observed on hot plate performance between morphine and morphine in combination with SJP-005. In conclusion, the findings in the von Frey up-and-down test (Study 1) suggest that animals can withstand higher levels of painful stimuli when SJP-005 is co-administered. This may also suggest a possible opioid sparing effect. However, in the hot plate test (Study 2), animals did not respond more adaptively to stronger painful stimuli after co-administering SJP-005. These observations warrant further investigation of the antinociceptive properties of SJP-005.
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spelling pubmed-79163402021-03-01 A Comparison of the Antinociceptive Properties of SJP-005 and Morphine in Rats Verster, Joris C Scholey, Andrew Dahl, Thomas A Iversen, Jacqueline M Pharmaceutics Article SJP-005 (a combination of ketotifen and ibuprofen) is being developed as a potential treatment for pain and for opioid use disorder. It is therefore important to investigate the potential antinociceptive properties of SJP-005. Two studies were conducted to evaluate the potential effects of SJP-005 in rats. Study 1 applied the von Frey test to examine the antinociceptive effect of morphine with and without SJP-005 in adjuvant-induced hypersensitivity to tactile stimulation. In a double-blind, between-groups design, groups of rats (n = 10 each) received morphine at 3, 10, or 30 mg/kg bodyweight (bw) (subcutaneous injection) with or without SJP-005 (oral). Mechanic allodynia and paw volume were assessed before and after treatment. Study 2 utilized the hot plate test. Using a crossover design, groups of rats (n = 10 each) received either morphine at 3, 10, or 30 mg/kg bw (subcutaneous injection) preceded by oral administration of placebo (Week 1) or SJP-005 (Week 2). In Study 1, in the von Frey up-and-down test, Δ paw withdrawal responses in Group 1 (3 mg/kg bw morphine) were significantly lower compared to those in Group 4 (3 mg/kg bw morphine plus SJP-005), whereas the differences in Δ paw withdrawal between Group 2 and Group 5 (10 mg/kg bw morphine with and without SJP-005) and between Group 3 and Group 6 (10 mg/kg bw morphine with and without SJP-005) did not reach statistical difference. Trendline analysis of the dose–response relationship for the morphine + placebo groups and morphine + SJP-005 groups revealed no significant differences in the intercepts and slopes. In Study 2, no significant differences were observed on hot plate performance between morphine and morphine in combination with SJP-005. In conclusion, the findings in the von Frey up-and-down test (Study 1) suggest that animals can withstand higher levels of painful stimuli when SJP-005 is co-administered. This may also suggest a possible opioid sparing effect. However, in the hot plate test (Study 2), animals did not respond more adaptively to stronger painful stimuli after co-administering SJP-005. These observations warrant further investigation of the antinociceptive properties of SJP-005. MDPI 2021-02-10 /pmc/articles/PMC7916340/ /pubmed/33578710 http://dx.doi.org/10.3390/pharmaceutics13020243 Text en © 2021 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
Verster, Joris C
Scholey, Andrew
Dahl, Thomas A
Iversen, Jacqueline M
A Comparison of the Antinociceptive Properties of SJP-005 and Morphine in Rats
title A Comparison of the Antinociceptive Properties of SJP-005 and Morphine in Rats
title_full A Comparison of the Antinociceptive Properties of SJP-005 and Morphine in Rats
title_fullStr A Comparison of the Antinociceptive Properties of SJP-005 and Morphine in Rats
title_full_unstemmed A Comparison of the Antinociceptive Properties of SJP-005 and Morphine in Rats
title_short A Comparison of the Antinociceptive Properties of SJP-005 and Morphine in Rats
title_sort comparison of the antinociceptive properties of sjp-005 and morphine in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916340/
https://www.ncbi.nlm.nih.gov/pubmed/33578710
http://dx.doi.org/10.3390/pharmaceutics13020243
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