The Role of Prolactin in the Sex Differences of Pruritus

Abstract

Background: Mechanisms promoting itch sensations may be sexually dimorphic. Previous studies have shown that application of pruritogens elicits a greater activation of brain structures that are believed to be involved in the central processing of itch in healthy women when compared to men. In addition, women with chronic pruritus experience more itch attacks and scratch lesions and during pregnancy, many women develop a dramatic increase in itch that may reduce their quality of life. However, whether the observed greater prevalence of certain itch conditions in women is based on sexually dimorphic mechanisms of itch is unknown. Here, we investigated whether the PRL/PRLR signaling system can activate, or sensitize, pruritoceptors (itch-selective neurons) as a possible mechanism that may contribute to the higher prevalence of certain itch conditions in women. Methods: We used an established cheek model of itch to first observe the effects of local PRL on the induction of acute itch development by performing a single intradermal injection of PRL to the right facial cheek of CD1 (ICR) mice. Immediately after the injections, the behaviors were recorded for thirty-minutes. We next observed whether the pretreatment of local PRL could enhance acute pruritus that is induced by the known pruritogens: chloroquine phosphate or histamine. For these experiments, we performed a single intradermal injection of PRL to the right facial cheek of CD1 (ICR) mice and one-hour afterwards we administered either chloroquine or histamine at the same site. The behaviors were also recorded for thirty-minutes. Since stress is known to increase circulating levels of PRL, we determined if repeated stress would sensitize the animals to chloroquine-induced itch. For these experiments, we subjected ICR mice to restraint stress (RS) for three-consecutive days for two-hours. On the last day of RS induction (Day 3), we performed a single intradermal injection of chloroquine or the control to the right facial cheek and recorded the behaviors afterwards for thirty-minutes. To determine if repeated stress produces a priming effect, we waited fifteen days (Day 15) after the first day of RS and induced acute pruritus and recorded behavior. Next, to confirm the results of the Day 15 experiment, we performed the induction of acute pruritus on the seventeenth day (Day 17) after the first day of RS induction and recorded behavior. Results: We found that local PRL injections do not induce acute itch development in either male or female mice. Additionally, pretreatment with PRL did not enhance or potentiate acute pruritus induced by chloroquine or histamine in either sex. Repeated stress, which increases circulating levels of PRL, does not induce acute itch development nor did it enhance chloroquine-induced itch in either sex. In contrast, stress decreased chloroquine-induced itch in both sexes. Finally, stress induced priming did not promote acute itch behaviors in female and male mice. Conclusion: The PRL/PRLR signaling system neither activated nor sensitized pruritoceptors. Therefore, the PRL/PRLR signaling system does not explain the increased prevalence of itch disorders in females.