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A Longitudinal Study to Evaluate Pregnancy-Induced Endogenous Analgesia and Pain Modulation
  1. Brendan Carvalho, MBBCh, FRCA*,
  2. Michal Granot, PhD,
  3. Pervez Sultan, FRCA,
  4. Hilary Wilson, MD§ and
  5. Ruth Landau, MD
  1. From the *Department of Anesthesiology, Perioperative and Pain Stanford University Medical Center, Stanford, CA; †Department of Nursing, Faculty of Social Welfare and Health Studies, University of Haifa, Haifa, Israel; ‡University College London Hospital, London, UK; §Evidera, Bethesda, MD; and ∥Columbia University, New York, NY
  1. Address correspondence to Brendan Carvalho, MBBCh, FRCA, Department of Anesthesia, H3580 Stanford University School of Medicine, Stanford, CA 94305 (e-mail: bcarvalho{at}


Background and Objectives The phenomenon of pregnancy-induced analgesia has been demonstrated in animal models but less consistently in human studies. This study aimed to assess endogenous pain modulation, evaluating inhibitory and excitatory pain pathways, over the course of pregnancy and postpartum.

Methods Healthy pregnant women were approached for participation in this prospective multicenter cohort study. Conditioned pain modulation (CPM), mechanical temporal summation (mTS), and temperature that induced pain 6 out of 10 (pain-6) were assessed toward the end of each trimester of pregnancy (8–12, 18–22, and 36 weeks) and at 6 to 12 weeks postpartum. To assess how pregnancy affects CPM, mTS, and pain-6, a mixed-effects analysis of variance was performed.

Results Thirty-three pregnant women were enrolled. Pregnancy did not significantly impact CPM (F3,39 = 0.30, P = 0.83, partial η2 = 0.02), and there was no significant difference between CPM scores in the third trimester compared with postpartum. The mTS scores and pain-6 ratings were also not significantly changed by pregnancy (F3,42 = 1.20, P = 0.32, partial η2 = 0.08; and F3,42 = 1.90, P = 0.14, partial η2 = 0.12, respectively).

Conclusions This is the first study to assess CPM and mTS changes in pregnancy and postpartum. Endogenous pain modulation evaluating both inhibitory and excitatory pain pathways did not significantly change during pregnancy or postpartum. Future studies are required to determine the magnitude and clinical significance of pregnancy-induced analgesia.

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  • The study was conducted at Lucile Packard Children's Hospital, Department of Anesthesia, Stanford University, Stanford, CA; and Department of Anesthesiology and Pain Medicine, University of Washington Medical Center, Seattle, WA.

    Institutional review board approvals were received at both Stanford University and University of Washington.

    The study was supported by the Department of Anesthesia, Perioperative and Pain Medicine, Stanford University, and Department of Anesthesiology and Pain Medicine, University of Washington. No external funding sources were used.

    The authors declare no conflict of interest.