Analgesic effects of peripherally administered opioids in clinical models of acute and chronic inflammation

Raymond A. Dionne, Allen M. Lepinski, Sharon M. Gordon, Louay Jaber, Jaime S. Brahim, Kenneth M Hargreaves

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

A series of double-blind, placebo-controlled clinical trials demonstrated that low doses of morphine (0.4, 1.2, and 3.6 mg) administered into the intraligamentary space of a chronically inflamed hyperalgesic tooth produced a dose-related naloxone-reversible analgesia. This analgesic effect is mediated by a local mechanism in the inflamed tissue, because subcutaneous administration of a 1.2 mg dose of morphine failed to elicit an analgesic response. In contrast, submucosal administration of 1.2 mg morphine or 50 μg fentanyl to the site of extraction of an impacted third molar after the onset of acute pain failed to elicit an analgesic response despite demonstration of a sensitive bioassay. These data indicate that peripheral opioid analgesia can be evoked in a model of chronic, but not acute, inflammatory pain, suggesting a temporal dependent mechanism needed for the expression of peripheral opiate analgesia during inflammation in humans.

Original languageEnglish (US)
Pages (from-to)66-73
Number of pages8
JournalClinical Pharmacology and Therapeutics
Volume70
Issue number1
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Analgesia
Morphine
Opioid Analgesics
Analgesics
Acute Pain
Inflammation
Opiate Alkaloids
Third Molar
Subcutaneous Tissue
Controlled Clinical Trials
Fentanyl
Naloxone
Biological Assay
Tooth
Placebos

ASJC Scopus subject areas

  • Pharmacology

Cite this

Analgesic effects of peripherally administered opioids in clinical models of acute and chronic inflammation. / Dionne, Raymond A.; Lepinski, Allen M.; Gordon, Sharon M.; Jaber, Louay; Brahim, Jaime S.; Hargreaves, Kenneth M.

In: Clinical Pharmacology and Therapeutics, Vol. 70, No. 1, 2001, p. 66-73.

Research output: Contribution to journalArticle

Dionne, Raymond A. ; Lepinski, Allen M. ; Gordon, Sharon M. ; Jaber, Louay ; Brahim, Jaime S. ; Hargreaves, Kenneth M. / Analgesic effects of peripherally administered opioids in clinical models of acute and chronic inflammation. In: Clinical Pharmacology and Therapeutics. 2001 ; Vol. 70, No. 1. pp. 66-73.
@article{6cf3784678c64d189112d027c2bc3811,
title = "Analgesic effects of peripherally administered opioids in clinical models of acute and chronic inflammation",
abstract = "A series of double-blind, placebo-controlled clinical trials demonstrated that low doses of morphine (0.4, 1.2, and 3.6 mg) administered into the intraligamentary space of a chronically inflamed hyperalgesic tooth produced a dose-related naloxone-reversible analgesia. This analgesic effect is mediated by a local mechanism in the inflamed tissue, because subcutaneous administration of a 1.2 mg dose of morphine failed to elicit an analgesic response. In contrast, submucosal administration of 1.2 mg morphine or 50 μg fentanyl to the site of extraction of an impacted third molar after the onset of acute pain failed to elicit an analgesic response despite demonstration of a sensitive bioassay. These data indicate that peripheral opioid analgesia can be evoked in a model of chronic, but not acute, inflammatory pain, suggesting a temporal dependent mechanism needed for the expression of peripheral opiate analgesia during inflammation in humans.",
author = "Dionne, {Raymond A.} and Lepinski, {Allen M.} and Gordon, {Sharon M.} and Louay Jaber and Brahim, {Jaime S.} and Hargreaves, {Kenneth M}",
year = "2001",
doi = "10.1067/mcp.2001.116443",
language = "English (US)",
volume = "70",
pages = "66--73",
journal = "Clinical Pharmacology and Therapeutics",
issn = "0009-9236",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Analgesic effects of peripherally administered opioids in clinical models of acute and chronic inflammation

AU - Dionne, Raymond A.

AU - Lepinski, Allen M.

AU - Gordon, Sharon M.

AU - Jaber, Louay

AU - Brahim, Jaime S.

AU - Hargreaves, Kenneth M

PY - 2001

Y1 - 2001

N2 - A series of double-blind, placebo-controlled clinical trials demonstrated that low doses of morphine (0.4, 1.2, and 3.6 mg) administered into the intraligamentary space of a chronically inflamed hyperalgesic tooth produced a dose-related naloxone-reversible analgesia. This analgesic effect is mediated by a local mechanism in the inflamed tissue, because subcutaneous administration of a 1.2 mg dose of morphine failed to elicit an analgesic response. In contrast, submucosal administration of 1.2 mg morphine or 50 μg fentanyl to the site of extraction of an impacted third molar after the onset of acute pain failed to elicit an analgesic response despite demonstration of a sensitive bioassay. These data indicate that peripheral opioid analgesia can be evoked in a model of chronic, but not acute, inflammatory pain, suggesting a temporal dependent mechanism needed for the expression of peripheral opiate analgesia during inflammation in humans.

AB - A series of double-blind, placebo-controlled clinical trials demonstrated that low doses of morphine (0.4, 1.2, and 3.6 mg) administered into the intraligamentary space of a chronically inflamed hyperalgesic tooth produced a dose-related naloxone-reversible analgesia. This analgesic effect is mediated by a local mechanism in the inflamed tissue, because subcutaneous administration of a 1.2 mg dose of morphine failed to elicit an analgesic response. In contrast, submucosal administration of 1.2 mg morphine or 50 μg fentanyl to the site of extraction of an impacted third molar after the onset of acute pain failed to elicit an analgesic response despite demonstration of a sensitive bioassay. These data indicate that peripheral opioid analgesia can be evoked in a model of chronic, but not acute, inflammatory pain, suggesting a temporal dependent mechanism needed for the expression of peripheral opiate analgesia during inflammation in humans.

UR - http://www.scopus.com/inward/record.url?scp=0034912403&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034912403&partnerID=8YFLogxK

U2 - 10.1067/mcp.2001.116443

DO - 10.1067/mcp.2001.116443

M3 - Article

C2 - 11452246

AN - SCOPUS:0034912403

VL - 70

SP - 66

EP - 73

JO - Clinical Pharmacology and Therapeutics

JF - Clinical Pharmacology and Therapeutics

SN - 0009-9236

IS - 1

ER -