Developmental neurobiology of neonatal pain

Newborns feel pain much as adults do, at lower stimulus thresholds, so procedural pain must be prevented and treated; oral sucrose works for single minor procedures, but it is not a cure-all.

1. The infant pain network resembles the adult one. In an fMRI study, noxious stimulation activated 18 of the 20 brain regions active in adults, including regions encoding sensory and affective components of pain ¹.
2. Two regions were quiet. The amygdala and orbitofrontal cortex were not significantly activated in newborns, and adult regions such as olfactory cortex, cuneus and fusiform gyrus were also inactive ¹.
3. Thresholds are lower, roughly fourfold. A 128 mN pinprick activated 14% of infant brain voxels, a pattern most like the adult response to 512 mN, which activated 9%; in adults 128 mN activated under 1% ¹.
4. Repeated pain matters. AAP warns that repeated painful exposures may have deleterious consequences, and the smallest, sickest preterm infants face the most painful procedures ².
5. Every unit needs a plan. AAP calls for every facility caring for neonates to have a program minimizing the number of painful procedures, plus routine pain assessment and pharmacologic and nonpharmacologic prevention for minor procedures ².
6. Sucrose works for single events. Oral sucrose reduces pain from heel lance, venipuncture and intramuscular injection in preterm and term infants; reported adverse effects were minor and similar to controls, with no serious harms documented ³.

Sucrose does not reduce circumcision pain, and its long-term neurodevelopmental effects and repeated-dose safety are unknown; such procedures need other analgesia ³.

• High-quality evidence supports 24% sucrose with non-nutritive sucking or 0.5 mL orally for heel lance ³.
• 2 mL of 24% sucrose before venipuncture reduced PIPP pain scores ³.
• Sucrose combined with non-nutritive sucking appears more effective than sucrose alone (moderate quality) ³.
• Sucrose evidence for arterial puncture, nasogastric tube insertion, bladder catheterization and eye examinations is inconclusive ³.
• No optimal sucrose dose has been identified because effective doses varied among studies ³.
• AAP notes proven, safe therapies remain underused for routine minor painful procedures in neonates ².
• Infants showed visible leg withdrawal at every pinprick intensity tested, whereas adults showed no reflex withdrawal ¹.
• Developing pain circuitry depends on non-noxious sensory activity, and early injury can permanently alter pain processing ⁴.

• Assuming newborns perceive less pain because of immaturity; the infant experience closely resembles the adult one ¹.
• Relying on sucrose alone for circumcision, where it is ineffective ³.
• Treating sucrose as proven safe for repeated long-term use ³.
• Ignoring early pain exposure as inconsequential; early injury can permanently alter pain processing ⁴.