Summary s-1
1 introduction 1-1

PART I Pain management and research
2 Pain management and the intersection of pain and opioid use disorder 2-1
•	The scope of the problem of pain, 2-1
•	Opioid analgesics, 2-4
•	Nonopioid pharmacologic treatments, 2-16
•	Interventional pain therapies, 2-25
•	Nonpharmacologic treatments, 2-27
•	Differences in pain experiences and treatment effectiveness among
•	Subpopulations, 2-33
•	The intersection between pain and opioid use disorder, 2-36
•	References, 2-36

3 Progress and future directions in research on pain and opioid use disorder 3-1
•	Basic pain research, 3-1
•	The neurobiology of the reward pathway and the intersection of pain and opioid
•	Use disorder, 3-10
•	Preclinical and translational research, 3-13
•	Clinical research, 3-18
•	Intersection of pain and opioid use disorder, 3-26
•	Support for research, 3-33
•	Summary and recommendation, 3-34
•	References, 3-34

PART II Addressing the opioid epidemic
4 Trends in opioid use, harms, and treatment 4-1
•	Trends in prescription opioid use and misuse, 4-1
•	Heroin use and its relation to prescription opioid use, 4-15
•	Illicit opioid markets, 4-25
•	The current state of surveillance systems, 4-32
•	Recent developments in pharmaceutical treatment of opioid use disorder, 4-35
•	Trends in treatment of opioid overdose with naloxone, 4-46
•	Summary and recommendations, 4-48
•	References, 4-49

5 Evidence on strategies for addressing the opioid epidemic 5-1
•	Nature of the Evidence, 5-2
•	The Need for a Systems Approach, 5-4
•	Strategies for Restricting Supply, 5-10
•	Strategies for Influencing Prescribing Practices, 5-21
•	Strategies for Reducing Demand, 5-39
•	Strategies for Reducing Harm, 5-46
•	Summary and Recommendations, 5-58
•	References, 5-60

6 Opioid approval and monitoring by the U.S. Food and drug administration 6-1
•	Overview of the FDA’s regulatory process for prescription drugs and its application to opioids, 6-2
•	Public health dimensions of FDA drug regulation, 6-17
•	Key elements of an integrated decision-making framework for opioid
•	Regulation,6-22
•	Implementation of an integrated framework for opioid regulation, 6-25
•	Summary and recommendations, 6-40
•	References, 6-44
•	Annex table 6-1: extended-release(er)/long-acting (la) opioid post-marketing
•	Study requirements, 6-49

Appendixes
A Data sources and methods a-1
B Biographical sketches of committee members and consultants b-1
C Existing data sources on opioid use, misuse, overdose, and other harms c-1

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Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use

Effects of prenatal and postnatal maternal emotional stress on toddlers' cognitive and temperamental development.

Psychological stress during pregnancy increases the risk of childhood wheeze and asthma. However, the transmitting mechanisms remain largely unknown. Since epigenetic alterations have emerged as a link between perturbations in the prenatal environment and an increased disease risk we used whole genome bisulfite sequencing (WGBS) to analyze changes in DNA methylation in mothers and their children related to prenatal psychosocial stress and assessed its role in the development of wheeze in the child. We evaluated genomic regions altered in their methylation level due to maternal stress based of WGBS data of 10 mother-child-pairs. These data were complemented by longitudinal targeted methylation and transcriptional analyses in children from our prospective mother-child cohort LINA for whom maternal stress and wheezing information was available (n = 443). High maternal stress was associated with an increased risk for persistent wheezing in the child until the age of 5. Both mothers and children showed genome-wide alterations in DNA-methylation specifically in enhancer elements. Deregulated neuroendocrine and neurotransmitter receptor interactions were observed in stressed mothers and their children. In children but not in mothers, calcium- and Wnt-signaling required for lung maturation in the prenatal period were epigenetically deregulated and could be linked with wheezing later in children’s life.

/pdf/prenatal-maternal-stress-and-wheeze-in-children-novel-1539xbncag.pdf

Prenatal maternal stress and wheeze in children: novel insights into epigenetic regulation

Cortisol obtained from hair samples represents a retrospective biomarker of chronic stress experienced by the subject in previous months. Although hair cortisol levels have been used to study the relationship between maternal and neonatal stress levels in primates, this has not yet been performed in humans using a longitudinal design and focusing specifically on this association. Therefore, the objective of this study was to determine whether a relationship existed between maternal psychological stress and hair cortisol levels during pregnancy and postpartum, and neonatal hair cortisol levels. The sample consisted of 80 pregnant women and their 80 newborn infants. We conducted a longitudinal assessment of hair cortisol levels, psychological stress, anxiety, and depression in the three trimesters of pregnancy and postpartum. After childbirth, neonatal hair cortisol levels were also measured. We found that maternal hair cortisol levels in the first trimester negatively predicted neonatal hair cortisol levels. Perceived stress in the third trimester of pregnancy also predicted lower neonatal cortisol, whereas pregnancy-specific stress in the same trimester had a positive relation with neonatal cortisol. Cortisol is essential for embryonic and fetal development; consequently, if fetal synthesis of cortisol is affected by high maternal cortisol levels, such development could be impaired.

/pdf/newborn-infants-hair-cortisol-levels-reflect-chronic-3c6zq7szgr.pdf

Newborn infants' hair cortisol levels reflect chronic maternal stress during pregnancy.

Noise exposure accelerates the risk of cognitive impairment and Alzheimer's disease: Adulthood, gestational, and prenatal mechanistic evidence from animal studies

Background Relatively few studies have been made on neurobehavioral outcomes of prenatal maternal stress during the newborn period, and little research has focused on umbilical cord stress hormones including cortisol, adrenocorticotropic hormone (ACTH), norepinephrine, and epinephrine. Our objective was to investigate the effects of prenatal maternal life stressors on neonatal birth outcomes, neurobehavioral development, and stress-related hormones levels. Methods Participants were 142 mothers and their infants; 71 were selected as the prenatal life stressor exposed group and 71 as the control group matched on maternal age, gestational week, delivery type, socioeconomic and education status, and newborns' sex. Maternal life stressors during pregnancy were determined using the Life Events Scale for Pregnant Women. Neonatal neurobehavioral development was assessed with the Neonatal Behavioral Neurological Assessment. Umbilical cord plasma stress-related hormones, including ACTH, cortisol, norepinephrine, and epinephrine were measured using an enzyme-linked immunosorbent assay. Results In the prenatal life stressors exposed group, newborns had significantly lower birth weight, smaller head circumference ( p p p p p Conclusion Prenatal maternal stress may negatively affect fetal birth outcomes, neurobehavioral development and affect neonates' cord plasma ACTH, cortisol, norepinephrine, and epinephrine.

Maternal Stress in Gestation: Birth Outcomes and Stress-Related Hormone Response of the Neonates

BACKGROUND
Relatively few studies have been made on neurobehavioral outcomes of prenatal maternal stress during the newborn period, and little research has focused on umbilical cord stress hormones including cortisol, adrenocorticotropic hormone (ACTH), norepinephrine, and epinephrine. Our objective was to investigate the effects of prenatal maternal life stressors on neonatal birth outcomes, neurobehavioral development, and stress-related hormones levels.


METHODS
Participants were 142 mothers and their infants; 71 were selected as the prenatal life stressor exposed group and 71 as the control group matched on maternal age, gestational week, delivery type, socioeconomic and education status, and newborns' sex. Maternal life stressors during pregnancy were determined using the Life Events Scale for Pregnant Women. Neonatal neurobehavioral development was assessed with the Neonatal Behavioral Neurological Assessment. Umbilical cord plasma stress-related hormones, including ACTH, cortisol, norepinephrine, and epinephrine were measured using an enzyme-linked immunosorbent assay.


RESULTS
In the prenatal life stressors exposed group, newborns had significantly lower birth weight, smaller head circumference (p < 0.01, p < 0.01, respectively). Scores of Neonatal Behavioral Neurological Assessment were significantly reduced (p < 0.001). Cord plasma ACTH, norepinephrine, and epinephrine levels were significantly increased (p < 0.001), but cortisol levels were reduced (p < 0.001).


CONCLUSION
Prenatal maternal stress may negatively affect fetal birth outcomes, neurobehavioral development and affect neonates' cord plasma ACTH, cortisol, norepinephrine, and epinephrine.

Junan Zeng

Papers

Maternal Stress in Gestation: Birth Outcomes and Stress-Related Hormone Response of the Neonates

Maternal Stress in Gestation: Birth Outcomes and Stress-Related Hormone Response of the

Expression of neurogranin in hippocampus of rat offspring exposed to restraint stress and pulsed magnetic fields