Long-lasting delayed hyperalgesia after chronic restraint stress in rats-effect of morphine administration

Neurosci Res. 2003 Mar;45(3):277-83. doi: 10.1016/s0168-0102(02)00232-8.


Different effects upon the nociceptive response have been observed with exposure to acute and chronic stress in rats. In the present study we repeatedly submitted rats to restraint for 40 days, inducing hyperalgesia using the tail-flick test. A new session of acute stress was applied at the end of 40 days period, and the chronically-stressed animals demonstrated analgesia after forced swimming, but not after restraint. The effect of stress interruption for 14 or 28 days on the nociceptive threshold was then investigated. The basal tail-flick latency remained decreased for at least 28 days (hyperalgesic effect). Following the periods of suspension, the animals were submitted to new session of acute restraint, and stress-induced analgesia was observed only after 28 days of stress interruption. Thus, the mechanisms involved in the long-lasting hyperalgesia presented in this study are not exactly the same as those responsible for the analgesia induced by acute stressors. After 40 days of chronic stress treatment, morphine was injected i.p. (1.0, 5.0 mg/kg or saline). The repeatedly stressed rats displayed decreased morphine effects on nociception compared to unstressed controls. The tolerance of the response to morphine agrees with previous studies suggesting that chronic restraint stress could modify the activity of opioid systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chronic Disease
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / etiology
  • Morphine / administration & dosage*
  • Rats
  • Restraint, Physical
  • Stress, Physiological / complications
  • Stress, Physiological / drug therapy*
  • Time


  • Morphine