Differential development of antinociceptive tolerance to morphine and fentanyl is not linked to efficacy in the ventrolateral periaqueductal gray of the rat

Erin N. Bobeck, Rachel A. Haseman, Dana Hong, Susan Ingram, Michael M. Morgan

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Systemic administration of morphine typically produces greater tolerance than higher efficacy mu-opioid receptor (MOPr) agonists such as fentanyl. The objective of the present study was to test this relationship by measuring antinociceptive efficacy and tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray (vlPAG). MOPr agonist efficacy was evaluated by microinjecting the irreversible opioid receptor antagonist β-funaltrexamine hydrochloride (β-FNA) into the vlPAG prior to a dose-response analysis of morphine and fentanyl antinociception. In contrast to systemic administration of morphine and fentanyl, microinjection of these drugs into the vlPAG had similar efficacy as measured by similar reductions in maximal antinociception following β-FNA administration. Analysis of tolerance revealed a rightward shift in the dose-response curve to a single pretreatment with morphine, but not fentanyl. The magnitude of tolerance to morphine was comparable following 1, 4, or 8 pretreatments. Tolerance to fentanyl also was evident following 4 or 8 microinjections. These data are surprising in that antinociceptive efficacy appears to vary depending on the site of administration. Moreover, the similar efficacy following microinjection of morphine and fentanyl into the vlPAG was associated with comparable tolerance, with the 1 exception of no tolerance to acute administration of fentanyl. Perspective: These data reveal that antinociceptive tolerance following vlPAG administration of opioids develops rapidly and is evident with both morphine and fentanyl, and the magnitude is relatively consistent regardless of the number of pretreatments.

Original languageEnglish (US)
Pages (from-to)799-807
Number of pages9
JournalJournal of Pain
Volume13
Issue number8
DOIs
StatePublished - Aug 2012

Fingerprint

Periaqueductal Gray
Fentanyl
Morphine
Microinjections
mu Opioid Receptor
Narcotic Antagonists
Opioid Analgesics

Keywords

  • acute tolerance
  • analgesia
  • efficacy
  • Opioid
  • pain modulation

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Neurology
  • Clinical Neurology

Cite this

Differential development of antinociceptive tolerance to morphine and fentanyl is not linked to efficacy in the ventrolateral periaqueductal gray of the rat. / Bobeck, Erin N.; Haseman, Rachel A.; Hong, Dana; Ingram, Susan; Morgan, Michael M.

In: Journal of Pain, Vol. 13, No. 8, 08.2012, p. 799-807.

Research output: Contribution to journalArticle

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