Gonadal steroid hormone modulation of nociception, morphine antinociception and reproductive indices in male and female rats

Pain. 2003 Jun;103(3):285-302. doi: 10.1016/s0304-3959(02)00457-8.


The purpose of this study was to examine how gonadal steroid hormones modulate basal nociception and morphine antinociception relative to regulating reproduction in the adult rat. Male and female Sprague-Dawley rats were either gonadectomized (GDX) or sham-gonadectomized (sham); GDX males were implanted subcutaneously with capsules containing testosterone (T), estradiol (E2), dihydrotestosterone (DHT), E2 and DHT, or nothing (0). GDX females received E2, T, or empty (0) capsules immediately after surgery, and vehicle or progesterone (P4) injections at 4-day intervals. Basal nociception and morphine antinociception were tested 28 days after surgery on 50 degrees C and 54 degrees C hotplate tests, and reproductive behavior and physiology were assessed shortly thereafter. There were no significant differences in baseline hotplate latencies among the male treatment groups, but morphine was significantly more potent in sham and GDX+T males than in GDX+0 males. The ability of T to increase morphine's potency was approximated by its major metabolites E2 and DHT, given together but not alone. Baseline hotplate latencies were higher in sham females tested during diestrus than in those tested during estrus. Morphine was significantly more potent in sham females tested during proestrus and diestrus than in those tested during estrus. Baseline hotplate latencies were significantly higher, and morphine was significantly less potent in GDX+E2, GDX+E2/P4 and GDX+T females than in GDX+0 females. All group differences in basal nociception and morphine antinociception observed on the 50 degrees C hotplate test were smaller and generally non-significant on the 54 degrees C hotplate test. Steroid manipulations produced the expected changes in reproductive behaviors and steroid-sensitive organs. These results demonstrate that in adult rats, gonadal steroid manipulations, that are physiologically relevant, modulate (1) basal nociception in females but not males, and (2) morphine's antinociceptive potency in both males and females.

Publication types

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

MeSH terms

  • Animals
  • Castration / methods
  • Dihydrotestosterone / pharmacology*
  • Dihydrotestosterone / therapeutic use
  • Drug Combinations
  • Drug Interactions
  • Estradiol / physiology
  • Estrous Cycle / drug effects
  • Female
  • Gonadal Steroid Hormones / physiology*
  • Infusion Pumps, Implantable / veterinary
  • Male
  • Morphine / pharmacology*
  • Morphine / therapeutic use
  • Organ Size / drug effects
  • Ovariectomy / methods
  • Pain / drug therapy*
  • Pain Measurement / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Sex Characteristics
  • Sexual Behavior / drug effects*
  • Sexual Behavior / physiology
  • Testosterone / physiology
  • Vagina / cytology
  • Vagina / drug effects


  • Drug Combinations
  • Gonadal Steroid Hormones
  • Dihydrotestosterone
  • Testosterone
  • Estradiol
  • Morphine