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Preproenkephalin mRNA is regulated by an interaction between steroid hormones and nociceptive stimulation
D A Holtzman1, P J Brooks, D W Pfaff
1Department of Brain and Cognitive Sciences, University of Rochester, NY 14627, USA.
Abstract:
The expression of preproenkephalin (PPE) mRNA has previously been shown to be regulated by steroid hormones in the ventromedial nucleus of the hypothalamus (VMH) and to be regulated by noxious stimuli in the dorsal horn of the spinal cord (DH). The present in situ hybridization study in ovariectomized rats showed that PPE mRNA expression in both the 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 content per cell by 100% compared with vehicle-treated rats. Unilateral hindpaw injection of 5% formalin, as compared to saline, significantly increased mean PPE mRNA content per VMH cell in rats treated with vehicle or estradiol but not those treated with estradiol + progesterone. Regression analysis for mean PPE mRNA content per VMH cell as a function of intensity of hindpaw inflammation showed a significant positive correlation coefficient after vehicle and estradiol treatment (P < 0.02) but a strong trend towards a negative correlation coefficient after estradiol + progesterone treatment (P < 0.06). ANOVA for homogeneity of regression coefficients showed a significant difference across hormone groups (P < 0.01). In the lumbar DH, mean PPE mRNA content per cell was greater in rats injected with formalin than with saline and was greatest 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 the other hormone groups. No significant differences in mean PPE mRNA levels per DH cell were found among the rats treated with saline + hormone, saline + vehicle, formalin + vehicle, or uninjected rats. For all hormone groups combined, mean PPE mRNA per DH cell showed a significant positive regression on intensity of hindpaw inflammation (P < 0.05). Taken together these data are consistent with reports of increased pain threshold during pregnancy, descending control of antinociception from the basomedial hypothalamus and positive correlations between VMH levels of PPE mRNA and lordosis, a behavior evoked by somatosensory stimulation below nociceptive threshold.
Insights
Ovarian hormones and noxious stimuli interact to regulate preproenkephalin (PPE) mRNA expression in the hypothalamus and spinal cord. This interaction influences pain perception and antinociception, particularly in the ventromedial hypothalamus.
Area of Science:
- Neuroendocrinology
- Pain Research
- Molecular Biology
Background:
- Preproenkephalin (PPE) mRNA expression is modulated by steroid hormones in the hypothalamus and by noxious stimuli in the spinal cord.
- Understanding the interplay between hormones and pain pathways is crucial for pain management and understanding physiological responses to stimuli.
Purpose of the Study:
- To investigate the interactive effects of ovarian steroid hormones and noxious peripheral stimuli on PPE mRNA expression in the ventromedial hypothalamus (VMH) and dorsal horn (DH) of ovariectomized rats.
- To explore the relationship between hormone treatment, noxious stimuli, and PPE mRNA levels in specific brain and spinal cord regions.
Main Methods:
- In situ hybridization was employed to quantify PPE mRNA expression in the VMH and lumbar DH of ovariectomized rats.
- Rats were treated with vehicle, estradiol, or estradiol + progesterone, and received unilateral hindpaw injections of formalin (noxious stimulus) or saline.
- Statistical analyses, including ANOVA and regression analysis, were used to assess the effects of hormone treatment and formalin injection on PPE mRNA levels and their correlations.
Main Results:
- In the VMH, estradiol or estradiol + progesterone increased PPE mRNA content per cell. Formalin injection increased PPE mRNA in vehicle and estradiol groups but not in the estradiol + progesterone group.
- A positive correlation between inflammation intensity and VMH PPE mRNA was observed with vehicle and estradiol, while a trend towards a negative correlation was seen with estradiol + progesterone.
- In the lumbar DH, formalin increased PPE mRNA, with the highest levels observed in rats receiving steroids + formalin. Ipsilateral expression was higher in estradiol-treated rats.
Conclusions:
- Ovarian steroid hormones and noxious stimuli interact to regulate PPE mRNA expression in both the VMH and lumbar DH.
- These findings support the concept of descending control of antinociception from the hypothalamus and align with observations of increased pain threshold during pregnancy.
- The study highlights the complex neuroendocrine mechanisms underlying pain modulation and hormone-environment interactions.