Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Robinson, Douglas L., Nag, Subodh, Mokha, Sukhbir S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2018
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
_version_ 1783329374752210944
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
work_keys_str_mv AT robinsondouglasl negativemodulationofspinalkopioidreceptormediatedantinociceptionbytheμopioidreceptoratselectivedosesofpentazocine
AT nagsubodh negativemodulationofspinalkopioidreceptormediatedantinociceptionbytheμopioidreceptoratselectivedosesofpentazocine
AT mokhasukhbirs negativemodulationofspinalkopioidreceptormediatedantinociceptionbytheμopioidreceptoratselectivedosesofpentazocine