Sex differences in the antagonism of swim stress-induced analgesia: effects of gonadectomy and estrogen replacement

Pain. 1993 Apr;53(1):17-25. doi: 10.1016/0304-3959(93)90050-Y.


Sex differences in the neurochemical mediation of swim stress-induced analgesia (SSIA) were examined in Swiss-Webster mice. Intact and gonadectomized adult mice of both sexes were tested for their analgesic response (hot-plate test) to 3 min of forced swimming in 15 degrees C and 20 degrees C water. SSIA resulting from 15 degrees C swim was previously shown to be naloxone-insensitive (i.e., non-opioid) whereas SSIA resulting from 20 degrees C swim produced an analgesia that was partially reversible by naloxone (i.e., mixed opioid/non-opioid). The non-opioid components of these SSIA paradigms were attenuated by the N-methyl-D-aspartate (NMDA) receptor antagonist, dizocilpine (MK-801). We now report that in males, but not females, dizocilpine (0.075 mg/kg, i.p.) and naloxone (10 mg/kg, i.p.) antagonized the non-opioid and opioid components of SSIA, respectively. After ovariectomy, females displayed a pattern of antagonism similar to males such that dizocilpine attenuated non-opioid SSIA, although naloxone remained ineffective in antagonizing 20 degrees C SSIA. Thus, SSIA in intact females was neither opioid- nor NMDA-mediated, yet it was of similar magnitude to the SSIA displayed by intact males. In separate experiments, estrogen replacement (estrogen benzoate; 5.0 micrograms/day, i.p.) administered to ovariectomized mice over a 6-8 day period reinstated the dizocilpine-insensitivity of 15 degrees C SSIA characteristic of intact females. However, a similar estrogen regimen administered to both intact and castrated males did not compromise the sensitivity to dizocilpine previously noted in male mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesia*
  • Animals
  • Body Weight
  • Dizocilpine Maleate / pharmacology
  • Estrogens / pharmacology*
  • Female
  • Male
  • Mice
  • Naloxone / pharmacology
  • Orchiectomy*
  • Ovariectomy*
  • Pain Measurement / drug effects
  • Reaction Time / drug effects
  • Sex Characteristics
  • Stress, Psychological / psychology*
  • Swimming


  • Estrogens
  • Naloxone
  • Dizocilpine Maleate