Morphine provides very little pain relief for premature babies, French researchers believe.
Evidence suggests premature babies can feel pain
They found the drug, which is very good for treating chronic pain in term babies and adults, did little to dull acute pain in 42 premature babies.
With these very sick infants needing hundreds of painful treatments and tests, more research is needed to find good relief, they told Paediatrics.
Untreated pain could do serious short and long term damage, they said.
Experts agreed the best way to treat pain in these babies was unclear.
The work by Dr Ricardo Carbajal and his team at the Hopital d'Enfants Armand Trouseau in Paris adds to recent research that found morphine had little effect on signs of distress of premature babies who were being ventilated to help them breathe.
In the latest study, Dr Carbajal looked at whether morphine alleviated pain associated with having a heel prick test - a way of taking a blood sample - among babies born up to three months premature and who were on neonatal intensive care wards.
Intravenous morphine appeared to be no better than an inactive dummy drug in relieving this acute pain.
The researchers used recognised scales that measure physical signs of distress, such as heart rate and facial expression, to score the pain.
Dr Carbajal said: "Our findings are very important. A lot of babies are born prematurely and go into intensive care units. Here they may need 100 or even more than 400 procedures in a very short space of time.
"There is now good evidence that premature babies can feel pain. We also know that pain can have important consequences. It can cause physiological disturbances, such as decreasing oxygen levels and increasing the pressures inside the head."
Studies have shown that babies who have a very painful procedure early in life behave differently to pain, such as that associated with vaccinations, later in infancy, he said.
"Although morphine is a very good drug for continuous, chronic pain in babies and adults, it does not seem to be good for acute procedural pain, lasting seconds or minutes, in these premature babies."
He said it was not known why morphine might not work, but suggested that premature babies might be too underdeveloped for the drug to be able to have an effect.
He said other synthetic drugs in the same opioid family as morphine appeared to work better, which might be related to their more rapid transit into the brain. Researchers also believe non-pharmacological interventions might help. Dr Carbajal said some studies had shown feeding babies a small amount of sugary water before painful procedures reduced pain scores.
Dr Gopi Menon, consultant neonatologist at Edinburgh University, said: "Morphine is very good for surgical pain for babies.
"But it is less clear how to treat premature babies with pain.
"There is now quite a lot of doubt about what to do. Morphine can have significant side effects.
"We need much more research. It is clear that premature babies do feel pain, even those born four months early."