Neonatal testosterone exposure influences neurochemistry of non-opioid swim stress-induced analgesia in adult mice.

The effects of neonatal hormone manipulations on swim stress-induced analgesia (SSIA) magnitude and neurochemical quality were examined in Swiss-Webster mice of both sexes. Previous research has indicated that non-opioid SSIA mechanisms in adult Swiss-Webster mice are sexually dimorphic. Male mice exhibit non-opioid SSIA following a 3-min swim in cold (15 degrees C) water that is antagonized by the non-competitive NMDA antagonist MK-801 (dizocilpine; 0.075 mg/kg), whereas female mice do not display NMDA-mediated analgesia in the presence of estrogen. Since male and female mice show equipotent magnitudes of SSIA, it was concluded that female mice display a neurochemically distinct, estrogen-dependent SSIA mechanism specific to their gender. In the present study, female mice exposed to testosterone during the neonatal period display NMDA-mediated analgesia even in the presence of estrogen in adulthood. Thus, expression of the female-specific, estrogen-dependent SSIA mechanism previously described may be dependent on the absence of testosterone during early ontogeny.

Morphine attenuates surgery-induced enhancement of metastatic colonization in rats.

Painful stressors such as surgery have been shown both to suppress immune function and to enhance tumor development. Whether the immune system mediates the tumor-enhancing effects of surgery remains unclear. Moreover, the role of postoperative pain has been largely ignored in such studies. To explore these issues, we used the MADB106 tumor, a mammary adenocarcinoma syngeneic to the subjects of this study (Fischer 344 rats) and known to be sensitive to natural killer (NK) cell activity. We found that surgery enhanced metastatic colonization and that this tumor-enhancing effect occurred only during the time in which the MADB106 tumor is sensitive to NK control. These results support the hypothesis that suppression of NK cell activity mediates the surgery-induced enhancement of metastatic colonization. Further, we found that an analgesic dose of morphine blocked the surgery-induced increase in metastasis without affecting metastasis in unoperated animals. These findings suggest that postoperative pain is a critical factor in promoting metastatic spread. If a similar relationship between pain and metastasis occurs in humans, then pain control must be considered a vital component of postoperative care.

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

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)