Infant Pain Modifies Stress and Anxiety Response in Later Life


Our brains get input through our sense organs. In the case of pain, the input is relayed by special sensory neurons, called nociceptors.

We know that nociceptors contain receptors which can detect one or more harmful stimuli, such as excess pressure, extreme cold or hot, or dangerous chemicals. Or pain.

But what happens to a developing brain when it is subject to more than the usual levels of painful stimulus?

In recent research, neuroscientists at Georgia State University have discovered that early life pain changes neural circuits in the brain that deal with stress.

The finding suggests that pains experienced by infants, who typically do not receive analgesics while undergoing tests and treatment in neonatal intensive care, may permanently revise future responses to anxiety, stress and pain in adulthood.

It is estimated that 12 percent of live births in the U.S. are considered premature, said the researchers, led by Dr. Anne Murphy, associate director of the Neuroscience Institute at Georgia State University.

“While a dampened response to painful and stressful situations may seem advantageous at first, the ability to respond appropriately to a potentially harmful stimulus is necessary in the long term,” Dr. Murphy said.

Neonatal Intensive Care Stress

These infants may spend an average of 25 days in neonatal intensive care.

They can undergo 10-to-18 painful and inflammatory procedures each day, including insertion of feeding tubes and intravenous lines, intubation and repeated heel lance.

In spite of evidence that pain and stress circuitry in the brain are established and functional in preterm infants, about 65 percent of these procedures are performed without benefit of analgesia.

Some clinical studies suggest early life pain has an immediate and long-term effect on responses to stress-provoking and anxiety-provoking events.

The neuropsychological effects on the bonding between mother and child, and on personal and social psychological well-being is hard to pin down. Research suggests that babies exposed to pain in the neonatal period have more difficulty in these areas.

Professionals working in the field of neonatal pain have speculated that adolescent aggression and self-destructive behaviour may, in some cases, be attributed to the long term effects of untreated neonatal pain.

Pain, Stress and Anxiety

This study investigated whether a single painful inflammatory procedure performed on male and female rat pups on the day of birth alters specific brain receptors that affect behavioral sensitivity to stress, anxiety and pain in adulthood.

The findings showed that such an experience is associated with site-specific changes in the brain that regulate how the pups responded to stressful situations.
Alterations in how these receptors function have also been linked with mood disorders.

The study findings back up what is now being reported clinically. Children who experienced unresolved pain following birth in fact, do show reduced responsiveness to pain and stress.

“The fact that less than 35 percent of infants undergoing painful and invasive procedures receive any sort of pre- or post-operative pain relief needs to be re-evaluated in order to reduce physical and mental health complications associated with preterm birth.”


Nicole C. Victoria, Kiyoshi Inoue, Larry J. Young, Anne Z. Murphy.
Long-term dysregulation of brain corticotrophin and glucocorticoid receptors and stress reactivity by single early-life pain experience in male and female rats.
Psychoneuroendocrinology, 2013; DOI:10.1016/j.psyneuen.2013.08.013

Anand KJS, Scalzo FM. Can Adverse Neonatal Experiences Alter Brain Development and Subsequent Behavior?
Biology of the Neonate, 2000: 77(2); 69-82

Last Updated on December 6, 2022