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Negative modulation of spinal κ-opioid receptor-mediated antinociception by the µ-opioid receptor at selective doses of (−)-pentazocine
The mixed-action κ-opioid receptor (KOR) agonist, pentazocine, binds to both KOR and the µ-opioid receptor (MOR). Racemic (±)-pentazocine and (−)-pentazocine, each administered systemically, have been shown to produce antinociception in various animal models. In contrast, racemic (±)-pentazocine fai...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988970/ https://www.ncbi.nlm.nih.gov/pubmed/29782380 http://dx.doi.org/10.1097/WNR.0000000000001043 |
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author | Robinson, Douglas L. Nag, Subodh Mokha, Sukhbir S. |
author_facet | Robinson, Douglas L. Nag, Subodh Mokha, Sukhbir S. |
author_sort | Robinson, Douglas L. |
collection | PubMed |
description | The mixed-action κ-opioid receptor (KOR) agonist, pentazocine, binds to both KOR and the µ-opioid receptor (MOR). Racemic (±)-pentazocine and (−)-pentazocine, each administered systemically, have been shown to produce antinociception in various animal models. In contrast, racemic (±)-pentazocine failed to produce antinociception when administered intrathecally (i.t.). However, whether spinal activation of KOR and MOR by (−)-pentazocine produces antinociception and the relative contribution of KOR and MOR in mediating antinociception remain unknown. Hence, we investigated whether i.t. (−)-pentazocine produces dose-dependent modulation of acute thermal nociception. Drugs were administered intrathecally in Sprague-Dawley rats and tail flick latency was recorded. Pentazocine produced a significant antinociceptive effect that was mediated by KOR and/or MOR at differential doses. MOR blockade restored the antinociceptive effect of an ineffective dose and prolonged the duration of an effective dose of pentazocine. Hence, spinal KOR and MOR mediated the effect of pentazocine. This study provides evidence that spinal MOR negatively modulates the KOR-mediated antinociceptive effect of i.t. pentazocine. |
format | Online Article Text |
id | pubmed-5988970 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-59889702018-06-19 Negative modulation of spinal κ-opioid receptor-mediated antinociception by the µ-opioid receptor at selective doses of (−)-pentazocine Robinson, Douglas L. Nag, Subodh Mokha, Sukhbir S. Neuroreport Integrative Systems The mixed-action κ-opioid receptor (KOR) agonist, pentazocine, binds to both KOR and the µ-opioid receptor (MOR). Racemic (±)-pentazocine and (−)-pentazocine, each administered systemically, have been shown to produce antinociception in various animal models. In contrast, racemic (±)-pentazocine failed to produce antinociception when administered intrathecally (i.t.). However, whether spinal activation of KOR and MOR by (−)-pentazocine produces antinociception and the relative contribution of KOR and MOR in mediating antinociception remain unknown. Hence, we investigated whether i.t. (−)-pentazocine produces dose-dependent modulation of acute thermal nociception. Drugs were administered intrathecally in Sprague-Dawley rats and tail flick latency was recorded. Pentazocine produced a significant antinociceptive effect that was mediated by KOR and/or MOR at differential doses. MOR blockade restored the antinociceptive effect of an ineffective dose and prolonged the duration of an effective dose of pentazocine. Hence, spinal KOR and MOR mediated the effect of pentazocine. This study provides evidence that spinal MOR negatively modulates the KOR-mediated antinociceptive effect of i.t. pentazocine. Lippincott Williams & Wilkins 2018-07-04 2018-06-06 /pmc/articles/PMC5988970/ /pubmed/29782380 http://dx.doi.org/10.1097/WNR.0000000000001043 Text en Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. |
spellingShingle | Integrative Systems Robinson, Douglas L. Nag, Subodh Mokha, Sukhbir S. Negative modulation of spinal κ-opioid receptor-mediated antinociception by the µ-opioid receptor at selective doses of (−)-pentazocine |
title | Negative modulation of spinal κ-opioid receptor-mediated antinociception by the µ-opioid receptor at selective doses of (−)-pentazocine |
title_full | Negative modulation of spinal κ-opioid receptor-mediated antinociception by the µ-opioid receptor at selective doses of (−)-pentazocine |
title_fullStr | Negative modulation of spinal κ-opioid receptor-mediated antinociception by the µ-opioid receptor at selective doses of (−)-pentazocine |
title_full_unstemmed | Negative modulation of spinal κ-opioid receptor-mediated antinociception by the µ-opioid receptor at selective doses of (−)-pentazocine |
title_short | Negative modulation of spinal κ-opioid receptor-mediated antinociception by the µ-opioid receptor at selective doses of (−)-pentazocine |
title_sort | negative modulation of spinal κ-opioid receptor-mediated antinociception by the µ-opioid receptor at selective doses of (−)-pentazocine |
topic | Integrative Systems |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988970/ https://www.ncbi.nlm.nih.gov/pubmed/29782380 http://dx.doi.org/10.1097/WNR.0000000000001043 |
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