January 27, 2010
Prenatal Alcohol Exposure Can Alter the Brain’s Developing Pain Regulatory System
Prenatal alcohol exposure is widely known to impair brain development in exposed offspring. Rodent studies have shown that developmental deficits in newborns related to altered levels of a brain chemical called serotonin (5-HT), leading to subsequent alterations in patterns of neonatal acute pain responses and/or hypothalamic-pituitary-adrenal (HPA) stress reactivity. New findings show a "blunted response" to an acutely painful event "“ a heel lance "“ in alcohol-exposed human newborns, indicating that prenatal alcohol exposure may alter the brain's developing pain regulatory system.
Results will be published in the April 2010 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.
"Timing is everything," said Tim F. Oberlander, a professor in the Division of Developmental Pediatrics at the BC Children's Hospital, the Child and Family Research Institute (CFRI), and the University of British Columbia. "The idea to look at pain responses in newborns with prenatal alcohol exposure came from two places," he said. "Since 1996, our group here in Vancouver had been studying acute pain reactivity and stress regulation in newborns of depressed mothers taking an SSRI antidepressant "“ such as Prozac "“ during their pregnancies. At the same time, Sandra Jacobson, a professor in the Department of Psychiatry and Behavioral Neurosciences at Wayne State University, and her collaborators had been studying stress regulation and development in alcohol-exposed children in Detroit and Cape Town, South Africa."
Oberlander, also one of the corresponding authors for the study, explained that since both serotonin reuptake inhibitors (SSRIs) and alcohol alter serotonin "“ which works to blunt or dampen pain pathways "“ they thought it would make sense to join together to look at how prenatal alcohol exposure influences pain-related biological and behavioral responses to a common painful event in the newborn period.
Teams from Oberlander's and Jacobson's laboratories worked with colleagues at the University of Cape Town, South Africa to recruit mothers during their third trimester of pregnancy. Their 28 infants were examined during the first few days of life: 14 who had been heavily exposed to alcohol prenatally, and 14 born to abstainers or light drinkers. Biobehavioral markers "“ salivary cortisol, heart rate, respiratory sinus arrhythmia, cardiac autonomic variability, and videotaped facial actions "“ were collected at three different times during heel-lance blood collection. After feeding and a nap, the newborns were also assessed on an abbreviated Brazelton Neonatal Behavioral Assessment Scale.
"Our study had three key findings," said Oberlander. "First, in alcohol exposed newborns, physiological responses to the heel lance, such as heart rate and parts of the nervous system that controls heart rate, were blunted or dampened compared to infants with little or no alcohol exposure. Second, we observed that, in response to this painful event, the stress hormone cortisol decreased in exposed infants while [remaining] almost unchanged in our control group. Finally, we looked at behavioral responses. Using very specific measures of facial expressions "“ a very well-accepted measure of newborn pain behavior "“ we found no differences between the two groups. However, using a measure of behavioral responsiveness called the Brazelton Neonatal Behavioral Assessment Scale, we found that the exposed infants were less aroused."
Oberlander explained that the "blunted response" to the heel lance may reflect something that alcohol does to the developing pain regulatory system in the brain. Previous studies by Jacobson and others had shown that prenatal alcohol exposure continues to affect infant reactivity up to one year of age.
"While the role of serotonin, the key pain regulatory chemical in prenatally exposed newborns, needs to be studied further, our findings are similar to those we observed in newborns with prenatal SSRI antidepressant exposure "“ medications that alter the level of serotonin in the developing brain," he explained. "We also noted that exposed infants were less behaviorally aroused in general. It is important to note that our infants had prolonged and heavy prenatal alcohol exposure, were not acutely intoxicated at birth, and were not experiencing a withdrawal period when we studied them. Together our findings reflect the effects of prolonged prenatal exposure and altered brain function and not an acute effect of alcohol exposure just before birth."
In summary, he added, the findings show that prenatal alcohol exposure changes critical areas of brain function very early in life, in this case specifically, important areas of brain function related to regulating pain responses.
"What these findings mean for long-term development and behavior is unknown at this point," he said. "However, we do know that altered stress regulation early in life can set up risk and vulnerability for poor mental and physical health and social and academic failure across the life span. In this sense, we think our findings may reflect a first glimpse at how prenatal alcohol exposure might 'calibrate' or 'program' emerging stress systems in early life."
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