Effects of local and spinal administrations of mu-opioids on postoperative pain in aged vs adult mice

Jennifer Mecklenburg, Mayur J. Patil, Wouter Koek, Armen N Akopian

Research output: Contribution to journalArticle

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Abstract

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 mg local; 1-15 mg spinal). Buprenorphine, a mixed mu-opioid agonist, produced dose-dependent antihypersensitivity with adult mice more sensitive to lower doses (0.1 mg local; 0.02 mg spinal), and aged mice more sensitive to higher doses (1, 10 mg local; 0.1, 1 mg 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.

Original languageEnglish (US)
Article numbere584
JournalPain Reports
Volume2
Issue number1
DOIs
StatePublished - Jan 1 2017

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Postoperative Pain
Opioid Analgesics
Ala(2)-MePhe(4)-Gly(5)-enkephalin
Nociception
Hypersensitivity
Pain
Buprenorphine
Locomotion
Age Groups
Hot Temperature
Injections

Keywords

  • Aged mice
  • Buprenorphine
  • Mu-opioids
  • Postoperative pain

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

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.

In: Pain Reports, Vol. 2, No. 1, e584, 01.01.2017.

Research output: Contribution to journalArticle

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AB - 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 mg local; 1-15 mg spinal). Buprenorphine, a mixed mu-opioid agonist, produced dose-dependent antihypersensitivity with adult mice more sensitive to lower doses (0.1 mg local; 0.02 mg spinal), and aged mice more sensitive to higher doses (1, 10 mg local; 0.1, 1 mg 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.

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