Measuring pain in neonates

Ensuring that infants undergoing medical procedures are not in pain is critically important, not least because we’ve learned in recent years that discomfort experienced early in life might have long term impacts on the brain and behaviour. Regrettably, we haven’t been very good at this previously, but now, as she explains to Chris Smith, Maria Cobo has developed a way to use brain activity to quantify pain and therefore the effectiveness of pain relief…

Maria - To give you some context, testing the effect of pain relief in newborns is very challenging because, unlike adults, they cannot report how much pain they are experiencing and understanding how much pain you are experiencing in the first place allows you then to test if a pain-relieving intervention is working or not. So, in our study, we wanted to find a way to reduce the sample sizes that we need, which can lead to a faster development of pain, relief interventions in babies.

Chris - Have people not already devoted a considerable amount of research effort to studying pain in neonates and infants for obvious reasons?

Maria - It is a very important topic. And, for sure, there are many groups investigating this area, but the metrics to assess pain have some limitations. So, for example, when a baby is monitored and experiences something painful, the heart rate may increase; the saturation may drop and you can see changes in the facial expression - a baby may start to cry. And this is usually how pain is assessed clinically. However, babies may also show the same type of responses, not necessarily when they are in pain. So these is why we have developed different methods to assess this.

Chris - And what were those?

Maria - So basically what we are using in our study is electroencephalography, which is a non-invasive technique. We place electrodes on the top of baby's head. And we basically are measuring the electrical activity when a baby experience, painful procedures.

Chris - And what are you comparing with what then? So just talk us through what you did to these infants, to get the data, and how you did the experiments.

Maria - What we did was a study, a total of 92 babies. And what we use is this EEG - or electroencephalography pattern of activity - that previously we have demonstrated that is present there when there is a painful stimulus, but not when we touch the baby or when a light or sound is presented to the baby. So we can say this measure is related to pain. In one set of babies we apply first a mild stimulus, which is just a gentle poke, and the way they respond to this mild poke allows us to predict how they will respond to a more intensive stimulus like blood test.

Chris - Right. So by doing the gentle prod, you can work out what particular fingerprint pattern of changes you get in the brain activity. So that is your pain signature. And when you do it more significantly with, as you say, a heel prick or blood test sampling, you see that same signature, but it's bigger and you can then standardize from that. So, you know, that is the signature of pain, that's our baseline. And when you extrapolate to other children with other interventions, you know, what you're comparing,

Maria - That's correct. Basically when we look at this response at baseline or to a mild stimulus, we can say how sensitive that baby is. So how intense is the response. And these also allow us to identify babies who are very high responders. So who, um, have a very intense response who may be actually those babies who can benefit most from the interventions. Uh, very interestingly, we found that interventions like gentle stroking of the leg before a blood test actually reduces the brain response to the blood test. And also in the last study we tested in a small group of babies paracetamol for immunisations. And we also found a positive effect.

Chris - Therefore, you can be both subjective and objective because you can, you can find individuals that are likely to respond more to a painful stimulus, and you can also therefore test how well you control the painful stimulus in those individuals. If we do this, it's painful. If we do this intervention, it makes it less painful.

Maria - That's correct. We are covering from the diagnostic tool itself of assessing if a baby is experiencing, uh, pain or the pain is subjective, we think we have a surrogate approximation of what is happening at the brain level. And, of course, this is then applicable when we are interested in testing interventions and things. Currently, there are no really medications or analgesics are not licensed to use in various small babies at the moment. So it could be a very important achievement if we can actually test these interventions faster and minimise the number of participants that we need.