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Effects of local and spinal administrations of mu-opioids on postoperative pain in aged vs adult mice
INTRODUCTION: Suboptimal management of postoperative pain leads to increased risk of chronic opioid therapy, especially in elderly patients. OBJECTIVES: Although this age-dependent phenomenon has been observed clinically, basic mechanisms including baseline nociception, postoperative hypersensitivit...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469295/ https://www.ncbi.nlm.nih.gov/pubmed/28626834 http://dx.doi.org/10.1097/PR9.0000000000000584 |
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author | Mecklenburg, Jennifer Patil, Mayur J. Koek, Wouter Akopian, Armen N. |
author_facet | Mecklenburg, Jennifer Patil, Mayur J. Koek, Wouter Akopian, Armen N. |
author_sort | Mecklenburg, Jennifer |
collection | PubMed |
description | INTRODUCTION: Suboptimal management of postoperative pain leads to increased risk of chronic opioid therapy, especially in elderly patients. OBJECTIVES: Although this age-dependent phenomenon has been observed clinically, basic mechanisms including baseline nociception, postoperative hypersensitivity, and mu-opioid efficiency in aged animals have never been evaluated. METHODS: We tested these criteria using incision model on adult (3–6 months) and aged (24 months) mice to assess translatability of postoperative animal studies to clinical observations. RESULTS: Thermal and mechanical testing revealed lower baseline nociception in aged vs adult mice, while behavioral assays after hind paw plantar incision showed similar hypersensitivity levels for both age groups. Efficiency of local and spinal mu-opioid injections on postoperative pain was assessed next. DAMGO, a pure mu-opioid, was effective in reducing postoperative hypersensitivity in aged and adult mice, although adult mice displayed increased sensitivity to higher doses (50 μg local; 1–15 μg spinal). Buprenorphine, a mixed mu-opioid agonist, produced dose-dependent antihypersensitivity with adult mice more sensitive to lower doses (0.1 μg local; 0.02 μg spinal), and aged mice more sensitive to higher doses (1, 10 μg local; 0.1, 1 μg spinal). Finally, exploratory locomotor activity was used to evaluate the suppression of incision-induced spontaneous pain by DAMGO. Spinal and systemic (intraperitoneal) DAMGO inhibited ongoing pain more in adults compared with aged mice. CONCLUSION: As in humans, baseline nociception was lower in aged vs adult mice, while postoperative hypersensitivity magnitudes were comparable between groups. Unlike in humans, adult mice were more sensitive to mu-opioids, although higher doses of mixed mu-opioids were more effective for postoperative antihypersensitivity in aged mice. |
format | Online Article Text |
id | pubmed-5469295 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Wolters Kluwer |
record_format | MEDLINE/PubMed |
spelling | pubmed-54692952018-01-01 Effects of local and spinal administrations of mu-opioids on postoperative pain in aged vs adult mice Mecklenburg, Jennifer Patil, Mayur J. Koek, Wouter Akopian, Armen N. Pain Rep Basic Science INTRODUCTION: Suboptimal management of postoperative pain leads to increased risk of chronic opioid therapy, especially in elderly patients. OBJECTIVES: Although this age-dependent phenomenon has been observed clinically, basic mechanisms including baseline nociception, postoperative hypersensitivity, and mu-opioid efficiency in aged animals have never been evaluated. METHODS: We tested these criteria using incision model on adult (3–6 months) and aged (24 months) mice to assess translatability of postoperative animal studies to clinical observations. RESULTS: Thermal and mechanical testing revealed lower baseline nociception in aged vs adult mice, while behavioral assays after hind paw plantar incision showed similar hypersensitivity levels for both age groups. Efficiency of local and spinal mu-opioid injections on postoperative pain was assessed next. DAMGO, a pure mu-opioid, was effective in reducing postoperative hypersensitivity in aged and adult mice, although adult mice displayed increased sensitivity to higher doses (50 μg local; 1–15 μg spinal). Buprenorphine, a mixed mu-opioid agonist, produced dose-dependent antihypersensitivity with adult mice more sensitive to lower doses (0.1 μg local; 0.02 μg spinal), and aged mice more sensitive to higher doses (1, 10 μg local; 0.1, 1 μg spinal). Finally, exploratory locomotor activity was used to evaluate the suppression of incision-induced spontaneous pain by DAMGO. Spinal and systemic (intraperitoneal) DAMGO inhibited ongoing pain more in adults compared with aged mice. CONCLUSION: As in humans, baseline nociception was lower in aged vs adult mice, while postoperative hypersensitivity magnitudes were comparable between groups. Unlike in humans, adult mice were more sensitive to mu-opioids, although higher doses of mixed mu-opioids were more effective for postoperative antihypersensitivity in aged mice. Wolters Kluwer 2017-01-15 /pmc/articles/PMC5469295/ /pubmed/28626834 http://dx.doi.org/10.1097/PR9.0000000000000584 Text en Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Basic Science Mecklenburg, Jennifer Patil, Mayur J. Koek, Wouter Akopian, Armen N. Effects of local and spinal administrations of mu-opioids on postoperative pain in aged vs adult mice |
title | Effects of local and spinal administrations of mu-opioids on postoperative pain in aged vs adult mice |
title_full | Effects of local and spinal administrations of mu-opioids on postoperative pain in aged vs adult mice |
title_fullStr | Effects of local and spinal administrations of mu-opioids on postoperative pain in aged vs adult mice |
title_full_unstemmed | Effects of local and spinal administrations of mu-opioids on postoperative pain in aged vs adult mice |
title_short | Effects of local and spinal administrations of mu-opioids on postoperative pain in aged vs adult mice |
title_sort | effects of local and spinal administrations of mu-opioids on postoperative pain in aged vs adult mice |
topic | Basic Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469295/ https://www.ncbi.nlm.nih.gov/pubmed/28626834 http://dx.doi.org/10.1097/PR9.0000000000000584 |
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