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Pain is a stressful situation which in children is usually underestimated, ignored and often untreated. It can cause anxiety with short- and long-term consequences such as physiological and behavioral changes as well as hormonal alterations (e.g., changes in the structure of corticospinal tract). Literature review has revealed many neuropetpides involved in the functional paths for pain transmission stimuli, including substance P (SP), neuropeptide Y, endorphins, enkephalins etc. Moreover, reports concerning the use of neuropeptides for the assessment of pediatric pain have increased in the recent years, involving situations such as migraine, venous and lumbar puncture. The investigation of objective indicators, such as neuropeptide levels, for assessing pain in children, as well as in persons unable to communicate, is of great interest for nursing assessment and care, for the reason that neuropeptide levels could constitute an objective measure of pain. Better assessment of pediatric pain will lead to better pain management in children.