Microinjection of the vehicle dimethyl sulfoxide (DMSO) into the periaqueductal gray modulates morphine antinociception

Erin N. Fossum, Mark J. Lisowski, Tara A. Macey, Susan Ingram, Michael M. Morgan

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Dimethyl sulfoxide (DMSO) is commonly used as a solvent for water-insoluble drugs. Given that DMSO has varying cellular and behavioral effects ranging from increased membrane permeability to toxicity, microinjection of DMSO as a vehicle could confound the effects of other drugs. For example, DMSO is often used as a vehicle for studies examining the neurochemical mechanisms underlying morphine antinociception. Given that the ventrolateral periaqueductal gray (vlPAG) plays a major role in morphine antinociception and tolerance, the effects of DMSO on morphine antinociception mediated by the vlPAG needs to be evaluated. The present experiment tested whether co-administration of DMSO (0, 0.2, 2, or 20%) would alter the antinociceptive effect of microinjecting morphine into the vlPAG. DMSO had no effect on nociception when microinjected into the vlPAG alone, but 2% DMSO enhanced morphine potency when co-administered with morphine. In contrast, twice daily microinjections of DMSO (5 or 20%) for two days reduced the potency of subsequent microinjections of morphine into the vlPAG-an effect that persisted for at least one week. A similar rightward shift in the morphine dose-response curve was caused by morphine tolerance. Co-administration of morphine and DMSO during the pretreatment did not cause a greater shift in the morphine dose-response curve compared to morphine pretreated alone. In conclusion, DMSO can alter morphine antinociception following both acute (enhancement) and chronic (inhibition) administration depending on the concentration. These data reinforce the need to be cautious when using DMSO as a vehicle for drug administration.

Original languageEnglish (US)
Pages (from-to)53-58
Number of pages6
JournalBrain Research
Volume1204
DOIs
StatePublished - Apr 14 2008
Externally publishedYes

Fingerprint

Periaqueductal Gray
Microinjections
Dimethyl Sulfoxide
Morphine
Pharmaceutical Preparations
Nociception
Permeability

Keywords

  • Analgesia
  • DMSO
  • Opioids
  • PAG
  • Vehicle

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Microinjection of the vehicle dimethyl sulfoxide (DMSO) into the periaqueductal gray modulates morphine antinociception. / Fossum, Erin N.; Lisowski, Mark J.; Macey, Tara A.; Ingram, Susan; Morgan, Michael M.

In: Brain Research, Vol. 1204, 14.04.2008, p. 53-58.

Research output: Contribution to journalArticle

Fossum, Erin N. ; Lisowski, Mark J. ; Macey, Tara A. ; Ingram, Susan ; Morgan, Michael M. / Microinjection of the vehicle dimethyl sulfoxide (DMSO) into the periaqueductal gray modulates morphine antinociception. In: Brain Research. 2008 ; Vol. 1204. pp. 53-58.
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