PREPROENKEPHALIN MESSENGER-RNA IS REGULATED BY AN INTERACTION BETWEENSTEROID-HORMONES AND NOCICEPTIVE STIMULATION

The expression of preproenkephalin (PPE) mRNA has previously been show n to be regulated by steroid hormones in the ventromedial nucleus of t he hypothalamus (VMH) and to be regulated by noxious stimuli in the do rsal horn of the spinal cord (DH), The present in situ hybridization s tudy in ovariectomized rats showed that PPE mRNA expression in both th e VMH and the lumbar DH, responds to the interaction between a noxious peripheral stimulus and ovarian steroid hormones. In the VMH, either estradiol or estradiol + progesterone increased the mean PPE mRNA cont ent per cell by 100% compared with vehicle-treated rats, Unilateral hi ndpaw injection of 5% formalin, as compared to saline, significantly i ncreased mean PPE mRNA content per VMH cell in rats treated with vehic le or estradiol but not those treated with estradiol + progesterone. R egression analysis for mean PPE mRNA content per VMH cell as a functio n of intensity of hindpaw inflammation showed a significant positive c orrelation coefficient after vehicle and estradiol treatment (P<0.02) but a strong trend towards a negative correlation coefficient after es tradiol + progesterone treatment (P<0.06), ANOVA for homogeneity of re gression coefficients showed a significant difference across hormone g roups (P<0.01). In the lumbar DH, mean PPE mRNA content per cell was g reater in rats injected with formalin than with saline and was greates t in rats given steroids + formalin, Mean PPE mRNA content per DH cell was greater ipsilateral than contralateral to the formalin injection in estradiol-treated rats, but no laterality difference was seen in th e other hormone groups. No significant differences in mean PPE mRNA le vels per DH cell were found among the rats treated with saline + hormo ne, saline + vehicle, formalin + vehicle, or uninjected rats, For all hormone groups combined, mean PPE mRNA per DH cell showed a significan t positive regression on intensity of hindpaw inflammation (P<0.05). T aken together these data are consistent with reports of increased pain threshold during pregnancy, descending control of antinociception fro m the basomedial hypothalamus and positive correlations between VMH le vels of PPE mRNA and lordosis, a behavior evoked by somatosensory stim ulation below nociceptive threshold.