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Pain. 2020 Jan;161(1):47-60. doi: 10.1097/j.pain.0000000000001709.

MicroRNA-19b predicts widespread pain and posttraumatic stress symptom risk in a sex-dependent manner following trauma exposure.

Author information

Institute for Trauma Recovery, University of North Carolina, Chapel Hill, NC, United States.
Departments of Anesthesiology and.
Biostatistics, University of North Carolina, Chapel Hill, NC, United States.
Department of Oral and Maxillofacial Surgery, University of California at San Francisco, San Francisco, CA, United States.
Department of Psychiatry, Texas A&M University Health Science Center, Bryan, TX, United States.
Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.
Department of Emergency Medicine, Henry Ford Hospital, Detroit, MI, United States.
Department of Emergency Medicine, University of Florida College of Medicine, Jacksonville, FL, United States.
Department of Emergency Medicine, Detroit Receiving, Detroit, MI, United States.
Department of Emergency Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.
Department of Emergency Medicine, Albert Einstein Medical Center, Philadelphia, PA, United States.
Department of Emergency Medicine, Sinai Grace, Detroit, MI, United States.
Department of Emergency Medicine, St Joseph Mercy Health System, Ann Arbor, MI, United States.
Departments of Psychology and Anesthesia, Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.
Department of Emergency Medicine, University of North Carolina, Chapel Hill, NC, United States.


Posttraumatic widespread pain (PTWP) and posttraumatic stress symptoms (PTSS) are frequent comorbid sequelae of trauma that occur at different rates in women and men. We sought to identify microRNA (miRNA) that may contribute to sex-dependent differences in vulnerability to these outcomes. Monte Carlo simulations (x10,000) identified miRNA in which predicted targeting of PTWP or PTSS genes was most enriched. Expression of the leading candidate miRNA to target PTWP/PTSS-related genes, miR-19b, has been shown to be influenced by estrogen and stress exposure. We evaluated whether peritraumatic miR-19b blood expression levels predicted PTWP and PTSS development in women and men experiencing trauma of motor vehicle collision (n = 179) and in women experiencing sexual assault trauma (n = 74). A sex-dependent relationship was observed between miR-19b expression levels and both PTWP (β = -2.41, P = 0.034) and PTSS (β = -3.01, P = 0.008) development 6 months after motor vehicle collision. The relationship between miR-19b and PTSS (but not PTWP) was validated in sexual assault survivors (β = -0.91, P = 0.013). Sex-dependent expression of miR-19b was also observed in blood and nervous tissue from 2 relevant animal models. Furthermore, in support of increasing evidence indicating a role for the circadian rhythm (CR) in PTWP and PTSS pathogenesis, miR-19b targets were enriched in CR gene transcripts. Human cohort and in vitro analyses assessing miR-19b regulation of key CR transcripts, CLOCK and RORA, supported the potential importance of miR-19b to regulating the CR pathway. Together, these results highlight the potential role that sex-dependent expression of miR-19b might play in PTWP and PTSS development after trauma/stress exposure.

[Available on 2021-01-01]

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