Peritraumatic 17β-estradiol levels influence chronic posttraumatic pain outcomes

Abstract

Biologic factors that predict risk for and mediate the development of common outcomes of trauma exposure such as chronic posttraumatic pain (CPTP) are poorly understood. In the current study, we examined whether peritraumatic circulating 17β-estradiol (E2) levels influence CPTP trajectories. 17β-estradiol levels were measured in plasma samples (n = 254) collected in the immediate aftermath of trauma exposure from 3 multiethnic longitudinal cohorts of men and women trauma survivors. Chronic posttraumatic pain severity was evaluated 6 weeks, 6 months, and 1 year after traumatic stress exposure. Repeated measures mixed models were used to test the relationship between peritraumatic E2 levels and prospective CPTP. Secondary analyses in a nested cohort assessed the influence of participant body mass index on the E2–CPTP relationship. In women, a statistically significant inverse relationship between peritraumatic E2 and CPTP was observed (β = −0.280, P = 0.043) such that higher E2 levels predicted lower CPTP severity over time. Secondary analyses identified an E2 * body mass index interaction in men from the motor vehicle collision cohort such that obese men with higher E2 levels were at greater risk of developing CPTP. In nonobese men from the motor vehicle collision cohort and in men from the major thermal burn injury cohort, no statistically significant relationship was identified. In conclusion, peritraumatic circulating E2 levels predict CPTP vulnerability in women trauma survivors. In addition, these data suggest that peritraumatic administration of E2 might improve CPTP outcomes for women; further research is needed to test this possibility.

Interleukin-10-producing monocytes contribute to sex differences in pain resolution in mice and humans

“…The role of estrogen in pain regulation, as well as IL-10 production, remains complex and enigmatic. While many pieces of evidence consistently support testosterone's protective role in pain relief [78][79][80][81] , contradictory results have emerged concerning the action of estrogen in pain modulation in both rodents [87][88][89][90][91][92] and humans 20,93,94 . Reports on the impact of estrogen on IL-10 production are also similarly perplexing and contradictory 71,[95][96][97][98][99] .…”

The influence of sex hormones on musculoskeletal pain and osteoarthritis

“…Estrogen is a key modulator of pain behaviour, but its effect depends on concentration; in females, estradiol is anti-nociceptive at higher concentrations (activating inhibitory pathways in the spinal cord) and pro-nociceptive at lower concentrations in both mice and men (84,85). In women who experienced trauma, lower levels of estradiol were associated with increased vulnerability to chronic pain (86). Progestogens are also antinociceptive, associated with pregnancy-induced analgesia in humans (87).…”

Does biological sex influence the mechanisms, assessment and treatment of pain? Disproportions in modern pain medicine

“…It has been observed that a higher level of estrogens in women reduces the risk of musculoskeletal pain or chronic post-traumatic pain [ 5 , 6 ]. Experimental studies have revealed differences in the analgesic effects of estrogens, also depending on the pain model – pain intensity in the inflammatory and visceral model, neuroprotective effect in models of neuropathic pain [ 7 ].…”