An opioidergic cortical antinociception triggering site in the agranular insular cortex of the rat that contributes to morphine antinociception

Adam R. Burkey, Earl Carstens, Julia J. Wenniger, Jinwen Tang, L. Jasmin

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98 Scopus citations


We report an anatomically defined opioid-responsive site in the rostral agranular insular cortex (RAIC) of the rat and characterize the antinociception produced by morphine acting within this region. Immunohistochemistry for the μ-opioid receptor identified a discretely localized cluster of densely labeled dendritelike processes in the agranular insular cortex. The antinociceptive effect of morphine microinjected unilaterally into this area was evaluated using the formalin test. Antinociception was observed in both ipsilateral and contralateral hindpaws. Local pretreatment with naltrexone in the RAIC blocked the antinociception of local morphine injection, confirming that morphine was acting at an opioid receptor. Unilateral injection of naloxone methiodide into the RAIC reversed the behavioral antinociception of systemic morphine bilaterally in the formalin test. Evidence for a descending inhibitory mechanism acting on spinal nociceptive neurons was obtained by monitoring noxious stimulus- induced c-fos expression in rats having undergoneformalin testing and by electrophysiological recording of single units in the lumbar dorsal horn after localized application of morphine into the RAIC. A significant reduction in the number of Fos-like immunoreactive neurons was found ipsilateral to the formalin stimulus in nociresponsive areas of the dorsal horn after on-site injections of morphine into the RAIC. Electrophysiological recording of nociresponsive dorsal horn neurons demonstrated a naloxone- reversible reduction in noxious thermal stimulus-evoked firing after morphine injection into this same area. These results suggest that the RAIC contributes to opioid-receptor-mediated antinociception after either local or systemic morphine administration and that these effects may be associated with an increased descending inhibition of dorsal horn neurons.

Original languageEnglish (US)
Pages (from-to)6612-6623
Number of pages12
JournalJournal of Neuroscience
Issue number20
StatePublished - Oct 15 1996


  • μ-opioid receptor
  • analgesia
  • cerebral cortex
  • descending inhibition
  • formalin test
  • Fos
  • limbic system
  • pain
  • systemic opioids

ASJC Scopus subject areas

  • Neuroscience(all)


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