Effect of λ-carrageenan-induced inflammatory pain on brain uptake of codeine and antinociception

Vincent S. Hau, Jason D. Huber, Christopher R. Campos, Ryan T. Davis, Thomas P. Davis

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

This study investigated the potential clinical implications of λ-carrageenan-induced inflammatory pain on brain uptake of a commonly used analgesic, codeine, in relation to the fundamental properties of the blood-brain barrier (BBB) correlated to its antinociceptive profile over a 168-h time course. BBB uptake of [14C]sucrose (a membrane impermeant marker) and [3H]codeine were investigated using an in situ brain perfusion model in the rat. Results demonstrated a significantly increased brain uptake of [14C]sucrose at 1, 3, 6 and 48 h (139±9%, 166±19%, 138±13% and 146±7% compared with control, respectively) and [3H]codeine at 3 and 48 h (179±6% and 179±12% compared with control, respectively). Capillary depletion analyses ensured that increased radioisotope associated with the brain was due to increased uptake rather than trapping in the cerebral vasculature. Antinociception studies using a radiant-heat tail flick analgesia method demonstrated that λ-carrageenan-induced inflammatory pain enhanced the in vivo antinociceptive profile of i.p.-administered codeine (7 mg/kg) at 3 and 48 h (144±11% and 155±9% compared with control, respectively). This study demonstrated that brain uptake and antinociception of codeine are increased during λ-carrageenan-induced inflammatory pain, suggesting that the presence of inflammatory pain may be an important consideration in therapeutic drug dosing, potential adverse effects and/or neurotoxicity.

Original languageEnglish (US)
Pages (from-to)257-264
Number of pages8
JournalBrain Research
Volume1018
Issue number2
DOIs
StatePublished - Aug 27 2004

Keywords

  • Antinociception
  • Blood-brain barrier
  • Brain uptake
  • Codeine
  • Inflammatory pain
  • Pain modulation: pharmacology
  • Sensory systems
  • λ-Carrageenan

ASJC Scopus subject areas

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

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