Lack of tolerance in peripheral opioid analgesia in mice

Shogo Tokuyama, Makoto Inoue, Takuya Fuchigami, Hiroshi Ueda

Research output: Contribution to journalArticlepeer-review


We recently developed a sensitive peripheral analgesic test in mice. Bradykinin, a representative pain-producing substance, when given subcutaneously through a polyethylene tube into the plantar of the limb connected to a transducer, induced a flexor reflex response, in a dose dependent manner. When morphine, a μ-opioid receptor agonist, was added to the plantar through another polyethylene tube, bradykinin-induced responses were completely abolished in a naloxone-reversible manner. These peripheral analgesic effects were also observed with DAMGO, another μ-opioid receptor agonist, and U-69,593, a δ-opioid receptor agonist, but not DSLET, a δ- opioid receptor agonist. When morphine was given subcutaneously to the back, a potent analgesia in the tail pinch test was observed. Repeated administrations of morphine once per day for 5 days showed a marked tolerance or reduction in morphine analgesia on the 6th day, while there was no significant reduction in the peripheral analgesia of morphine. These findings suggest that tolerance to morphine analgesia is mediated through synaptic plasticity in the central nervous system, but not through a receptor desensitization at the level of the single cell.

Original languageEnglish (US)
Pages (from-to)1677-1681
Number of pages5
JournalLife Sciences
Issue number17-18
StatePublished - Mar 27 1998
Externally publishedYes


  • Bradykinin
  • Morphine
  • Opioid
  • Peripheral analgesia
  • Tolerance

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)


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