Age-Dependent Sexual Dimorphism in Susceptibility to Develop Chronic Pain in the Rat. (1st September 2018)

• Record Type: Journal Article
• Authors: Ferrari, Luiz F.; Araldi, Dioneia; Green, Paul; Levine, Jon D.
• Is Part Of: Neuroscience. Volume 387(2018)
• Page Start: 170
• Page End: 177
• Publication Date: 2018-09-01
• Subjects: PGE2 prostaglandin E2 -- PKCε protein kinase C epsilon -- TNFα tumor necrosis factor α; hyperalgesic priming -- hyperalgesia -- nociceptor -- estrogen -- chronic pain -- rat; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2017.06.044
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: TNFα induces hyperalgesic priming in adult male, but not female, rats. In young males, induction of priming by TNFα is significantly attenuated. In young females, injection of TNFα induces robust priming. Estrogen modulates this difference in susceptibility to develop priming in both sexes. Our data help to explain development of sex differences in susceptibility to chronic pain in adults. Abstract: Neonatal pain has been suggested to contribute to the development and/or persistence of adult pain. Observations from animal models have shown that neonatal inflammation produces long-term changes in sensory neuron function, which can affect the susceptibility of adults to develop persistent pain. We used a preclinical model of transition to chronic pain, hyperalgesic priming, in which a previous inflammatory stimulus triggers a long-lasting increase in responsiveness to pro-algesic mediators, prototypically prostaglandin E2 (PGE2 ), to investigate if post-natal age influences susceptibility of adult rats to develop chronic pain. Priming was induced by tumor necrosis factor alpha (TNFα), in male and female rats, 1, 2, 3, 4, 5 or 7 weeks after birth. When adults (8 weeks after birth), to evaluate for the presence of priming, PGE2 was injected at the same site as TNFα. In males that had received TNFα at post-natal weeks 1, 2 or 3, priming was attenuated compared to the 4-, 5- and 7-week-old treated groups, in which robust priming developed. In contrast, in females treated with TNFα at post-natal week 1, 2, 3, or 4, but not at 5 or 7, priming was present. This age and sex difference in the susceptibility to priming was estrogen-dependent, since injection of TNFα in 3-week-old males and 5-week-old females, in the presence of the estrogen receptor antagonist ICI 182, 780, did produce priming. These results suggest that estrogen levels, which vary differently in males and females over the post-natal period, until they stabilize after puberty, impact pain as an adult.