Toronto --- Baby boys not only experience pain during circumcision, they actually remember the agony of their ordeal, researchers here say.

Chief investigator Anna Taddio said a year-long study of infant pain reaction during routine vaccination found that, despite the passing of four to six months, male infants circumcised without the benefit of analgesia exhibited more signs of pain during routine immunization than boys who had not had their foreskins removed or who underwent the procedure with a transdermal anesthetic.

"This study demonstrates that infants do in fact feel pain, and that a painful experience in the newborn period can affect pain behaviors later on," said Taddio, during an interview. "Given that's the case, it is our recommendation that every measure be taken to prevent pain in circumcision and other medical and surgical procedures."

Taddio, a PhD candidate at the University of Toronto's school of pharmacology, and colleagues at the Hospital for Sick Children (HSC) were prompted to embark on this line of investigation after an earlier study indicated male infants --- especially those who had been circumcised --- demonstrate a greater pain response to vaccination than do their female counterparts.

That observation resulted in a study which would determine whether pretreatment with lidocaine-prilocaine 5% cream (EMLA) affected the circumcised infant's pain response to immunization.

The researchers recruited 87 healthy, full-term male infants, 32 of whom were uncircumcised, 29 circumcised an hour after the application of 0.5 g - 1 g of EMLA 5% cream, and 26 who underwent the procedure without any pain relief.

Four to six months later, when routine vaccinations were due, the researchers arranged to video tape the immunization sessions, all of which took place at the primary care physician's clinic.

"We chose to study pain response during routine vaccination…to reduce the effects of fear and anticipation on infant pain response seen in older infants and children, and because vaccination pain responses do not vary greatly within this age range," explained Taddio, who was supervised by Dr. Gideon Koren, head of Clinical Pharmacology and Toxicology at HSC.

Parents completed an infant temperament questionnaire and were questioned about their baby's last feeding and nap times prior to the vaccination to ensure that the baby's temperament did not influence his reaction to the needle.

Vaccination procedure

The vaccination procedure was standardized across settings: infants were physically examined and given time to settle down before being placed supine on the examination table and given an intramuscular injection in the thigh using a 25-gauge needle. Video taping commenced a minimum of 20 seconds before vaccination and continued for up to a minute after the procedure was complete.

Pain response was later scored without knowledge of circumcision or treatment status by a research assistant trained to measure infant facial action (such as, brow bulge, nasolabial furrow and eyes squeezed shut), cry duration and visual analogue scale pain scores.

"This system is a sensitive and specific way of rating infant pain and is the most extensively used behavioral pain measure in infant pain research," said Taddio, "The neonatal facial system was chosen as the primary outcome measure for this study because it is considered to be the gold standard for infant pain assessment."

The three facial actions and cry duration were coded as present or absent for each subject 20 seconds before the vaccination (baseline), for 20 seconds during the injection and the first 20 seconds after the injection. These data were then converted into percentages of time that the infant exhibited the actions or cried.

The investigators noted that infants circumcised without anesthetic showed more pain than uncircumcised boys. Over a third of the circumcised infants showed pain using the facial action scale, compared to half that number for the uncircumcised. During 53.8% of the time the circumcised infants cried compared to just 24.7% of the time for the uncircumcised. The circumcised were scored higher on the visual analogue scale pain scale (5.1 cm on a 10 cm rule vs. 3.1 cm) than the uncircumcised.

As for babies treated with EMLA 5% cream prior to circumcision, their pain responses fell between the two groups.

'Higher pain'

"These results support our previous finding of a higher pain response in circumcised infants during routine immunization," said Taddio. "And they are consistent with previous studies in animals and adults showing that injury and tissue damage can influence behavioral responses to painful events months after the wound has healed."

Investigators speculate that the pain of circumcision may cause changes in the infant's central neural processing of painful stimuli. They suggest that peripheral noxious stimulation may lead to the sensitization of neuronal cells in the dorsal horn of the spinal cord, and in so doing alter their reaction to future pain stimuli.

"There is a common belief that the effects of circumcision pain are short-lived and clinically insignificant and, therefore, that the benefits of analgesics treatment do not outweigh the risks of adverse effects," she said.

"We can no longer make this assumption. Babies are just as worthy of analgesics as everybody else and we should make every effort to find ways of using them safely and effectively in this group."

Circumcision is the most common surgical procedure performed on Canadian newborns. About 60% of male infants in the U.S. are circumcised and the vast majority do not receive pre- and postoperative management of pain.