Opiate and non-opiate mechanisms of stress-induced analgesia: Cross-tolerance between stressors

Angela Spiaggia, Richard J. Bodnar, Dennis D. Kelly, Murray Glusman

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93 Scopus citations


Acute exposure to severe stressors induce profound analgesia. Repeated exposures to the same stressors esult in adaptation in much the same way that repeated administration of opiates results in tolerance. The present study investigated whether two qualitatively different stressors, cold-water swims (CWS) and injections of 2-deoxy-D-glucose (2-DG) share common pain-inhibitory mechanisms by determining whether cross-tolerance developed to their analgesic effects. Cross-tolerance was also examined between 2-DG and morphine. Flinch-jump thresholds were determined in six groups of six rats each. Analgesia was observed 30 min following acute exposure to CWS (2°C for 3.5 min), 2-DG (350 mg/kg) and morphine (10 mg/kg), but not following placebo injections or warm water swims. Chronic exposure to all three analgesic treatments resulted in tolerance and adaptation. Complete and reciprocal cross-tolerance developed between the analgesia induced by CWS and by DG. Complete cross-tolerance to 2-DG analgesia also developed in morphine-tolerant rats, but only partial cross-tolerance to morphine analgesia developed in 2-DG adapted rats. These results support the concept that stressful events induce analgesia through specific activation of an intrinsic pain-inhibitory system which has both opiate and non-opiate branches.

Original languageEnglish
Pages (from-to)761-765
Number of pages5
JournalPharmacology Biochemistry and Behavior
Issue number5
StatePublished - May 1979
Externally publishedYes


  • 2-Deoxy-D-glucose
  • Analgesia
  • Cold-water swims
  • Cross-tolerance
  • Morphine
  • Pain-inhibition
  • Rats
  • Stress


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