Stress-induced analgesia and endogenous opioid peptides: the importance of stress duration

Eur J Pharmacol. 2011 Jan 15;650(2-3):563-7. doi: 10.1016/j.ejphar.2010.10.050. Epub 2010 Oct 31.


Stress is known to elicit pain relief, a phenomenon referred to as stress-induced analgesia. Based on stress parameters, opioid and non-opioid intrinsic pain inhibitory systems can be activated. In the present study, we assessed whether changing the duration of stress would affect the involvement of endogenous opioids in antinociception elicited by swim in warm water (32 °C), known to be opioid-mediated. Using mice lacking beta-endorphin, enkephalins or dynorphins and their respective wild-type littermates, we assessed the role of each opioid peptide in antinociception induced by a short (3 min) vs. long (15 min) swim. Mice were tested for baseline hot plate latency, exposed to swim (3 or 15 min) in warm water (32 °C) and then tested for antinociception at 5, 15 and 30 min. Our results revealed that both swim paradigms induced significant antinociception in wild-type mice. However, the short swim failed to induce antinociception in beta-endorphin-deficient mice, illustrating that beta-endorphin is important in this form of stress-induced antinociception. On the other hand, antinociception elicited by the long swim was only slightly reduced in beta-endorphin-deficient mice despite pretreatment with naloxone, a non-selective opioid receptor antagonist, significantly attenuated the antinociception elicited by the long swim. Nevertheless, a delayed hyperalgesic response developed in mice lacking beta-endorphin following exposure to either swim paradigm. On the other hand, mice lacking enkephalins or dynorphins and their respective wild-type littermates expressed a comparable antinociceptive response and did not exhibit the delayed hyperalgesic response. Together, our results suggest that the endogenous opioid peptide beta-endorphin not only mediates antinociception induced by the short swim but also prevents the delayed hyperalgesic response elicited by either swim paradigm.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analgesia*
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Dynorphins / genetics
  • Dynorphins / physiology
  • Enkephalins / genetics
  • Enkephalins / physiology
  • Female
  • Hot Temperature
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Naloxone / pharmacology
  • Nociceptors / physiology
  • Opioid Peptides / genetics
  • Opioid Peptides / physiology*
  • Pain Measurement
  • Stress, Psychological / metabolism*
  • Stress, Psychological / physiopathology
  • Swimming
  • Time Factors
  • beta-Endorphin / genetics
  • beta-Endorphin / physiology


  • Analgesics, Opioid
  • Enkephalins
  • Opioid Peptides
  • Naloxone
  • beta-Endorphin
  • Dynorphins