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The pains of youth

2 Apr, 2009

As recently as the late 1980s, clinicians mistakenly believed that newborn babies did not feel pain. We are now beginning to understand just how different pain processing is in infants, progress that promises tremendous clinical benefits for those in intensive care.

Pain, unpleasant though may be, is an important function of our body, warning us if something is wrong or of a hazard to be avoided. It is tied in with our sense of touch and how we perceive different stimuli, and efforts to understand it have yielded tremendous clinical benefits, not least in the quest for better pain relief for patients.

One would assume that newborn babies, at their vulnerable stage in life, are particularly sensitive to pain. Yet, surprisingly, until the late 1980s it was widely assumed among clinicians that newborn infants did not feel pain.

“Largely it was based on ignorance – a rather simplistic view that if you can’t remember something then that means that you don’t process it,” says Maria Fitzgerald, Professor of Developmental Neurobiology at University College London. “There was a general view that all that babies did was cry and make a fuss, moving their arms and legs about.”

Professor Fitzgerald was among the first researchers to investigate infant pain. Her work is particularly pertinent given the number of babies that enter intensive care – particularly those born prematurely – needing to undergo a number of essential, but painful, procedures.

Audio: Professor Maria Fitzgerald of UCL on infant pain [2’56].

Early change

Our pain pathways undergo extensive structural and functional change after we are born. At first, the nervous system is not fine-tuned, with nerve cells underdeveloped and connections and circuits still raw.

“In very young babies there is a very strong, exaggerated, behavioural response to pain, much stronger than you would see in an older child or adult,” says Professor Fitzgerald.

Her latest research, funded by the Wellcome Trust, has revealed a fundamental difference between infant and adult pain pathways.

As adults, when we detect a painful stimulus, the sensory nervous system in the spinal cord suppresses the signal to a certain extent, reducing the intensity of the pain and helping us to detect exactly where it is in the body. Also, when the brain receives the pain signal, it sends inhibitory information back to the spinal cord.

But in newborn babies, this system has the opposite effect.

“The brain actually enhances the pain inputs rather than suppressing them. It’s a complete reverse of what happens in an adult,” says Professor Fitzgerald.

This makes sense in terms of development: a lot of sensory input at the early stages of the brain’s development helps the synapses and nerve pathways to grow. However, if the input is repeatedly painful, there can be damaging consequences.

“The importance of this is that if infants undergo a lot of painful procedures – as those in intensive care often do – far from the brain being able to control the pain that is coming in, if anything it enhances it,” says Professor Fitzgerald. “We don’t know if it is necessarily more painful, because we don’t know what babies feel, but certainly there is more of a painful input going in.”

Sensitivity paradox

What long-term effects does repeated exposure to pain have on a developing nervous system? Research has uncovered a strange paradox.

Children that have undergone a lot of intensive care when young seem to be less sensitive to things such as touch and temperature. But they are more sensitive to new pain stimuli.

“It’s quite an odd and complicated picture, almost like a contrast. The child is relatively less sensitive in its body but hypersensitive, it seems, to a new pain,” says Professor Fitzgerald.

Studies have also shown that if young rat pups have an injury, then later in life they are more sensitive to repeated injury in that same place.

“You might find that not surprising, but actually if you do the same thing in adult life they don’t maintain that long sensitisation,” says Professor Fitzgerald. “There’s something about having an injury very early in life that does seem to produce a very long-lasting sensitivity in that injured area.”

From tests to treatment

The fact that the infant nervous system is, in a sense, receiving more pain than in adults intensifies the need to look for better analgesics (pain-relieving drugs) for newborn babies.

Morphine is used during surgical procedures, but there are few approved infant pain-relief treatments. One, sucrose, is essentially just a sugar solution that encourages sucking, which has a sedative effect.

“Sucrose does pacify an infant, but when you’re doing repeated painful procedures day after day, it’s insufficient,” says Professor Fitzgerald. “It’s not really reducing the pain. We need to do some real trials of analgesics in young infants.”

But how do you measure how much pain an infant is feeling, and how effective the analgesics are? Even in adults pain measurements rely on a patient’s subjective descriptions: how much it hurts, or if it feels better or worse. Babies cannot describe what they feel, and their relative fragility rules out the use of techniques such as functional magnetic resonance imaging that require large equipment.

Funded by the Wellcome Trust and the Medical Research Council, Professor Fitzgerald’s team are working with colleagues at University College Hospital and Great Ormond Street Hospital in London on a combination of near infrared spectroscopy and electroencephalography. These measure the oxygenation of brain tissue and the electrical activity of neurons in the brain, respectively, both of which provide a more direct measure of pain than observing behavioural responses. Importantly, neither is invasive and both can be done cot-side.

“We’re trying to develop systems that we can use in human infants which will provide real measures of the outcomes of clinical trials,” says Professor Fitzgerald. “Once we’ve got that, then we can begin to translate the basic findings.”

Our new knowledge about the infant inhibitory system now needs building on, with better measures of how exactly it works. It’s the first step toward clinical treatments, with researchers then perhaps able to look for ways to re-establish inhibition in injured infants, or to stop the pain enhancement effect from happening in the first place.

Pain remains unpleasant, but research into it continues to further our understanding of human development and bring relief to all, old and young.

Image Credits: Wellcome Images
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