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Before the 1980s, it was a common belief that preterm infants lacked the neurodevelopmental capacity to feel pain. This resulted in severe undertreatment of pain in the neonate during their hospitalization. Although neonatology has made strides in the past 20 years to understand pain, it remains challenged to effectively assess and treat the various types of pain experienced in the neonatal intensive care unit (NICU).


  1. Definition. Pain has been defined by the International Association for the Study of Pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in such terms of such damage.” When an infant responds to pain, it involves a collection of biochemical, physiologic, and behavioral reactions. There are many different layers of an infant's response that can be understood by gestational age and development. Noxious stimuli lead to tissue damage, causing the release of sensitizing substances such as prostaglandins, bradykinin, serotonin, substance P, and histamine. These chemicals produce an impulse that is then transmitted to the nociceptive pathways. Nociception refers to the reflex movement occurring with exposure to noxious stimuli that does not require cortical involvement or the ability to perceive pain.

  2. Development. Development of sensory nerve endings begins very early in the process of nociception and follows as:

    1. 7.5–15 weeks' gestation. Peripheral cutaneous sensory receptors develop in the perioral, facial, palmar, and abdominal areas and proximal extremities.

    2. 8–19 weeks' gestation. Spinal reflexes are able to respond to noxious stimuli, and neurons populate the dorsal root ganglion.

    3. 20 weeks' gestation. Mucous membranes and remaining cutaneous areas are populated with sensory nerve endings.

    4. 20–24 weeks' gestation. Thalamic afferents involved in conscious perception of pain reach the subplate zone and the cortical plate.

    5. 23–27 weeks' gestation. Thalamic afferents reach the visual cortex.

    6. 26–28 weeks' gestation. Thalamic afferents reach the auditory cortical plate.

  3. Repeated exposure to noxious stimuli. This can cause physiologic and behavioral disorganization, leading to changes in the neurodevelopmental system of the infant. This may cause the infant to develop an inability to respond to pain or an exaggerated physiologic response to painful stimuli in the future.


  1. Birth trauma. Neonatal pain associated with birth trauma is typically a result of vacuum-assisted births. Some babies may show signs of bruising on the face or head simply as a result of the trauma of passing through the birth canal. Forceps deliveries can leave temporary marks or bruises on the baby's face and head. Cephalohematomas are more common with forceps delivery or vacuum extraction. Tylenol may be used for the treatment of associated pain. Collarbone fractures are the most common birth-related fracture. If the fracture is painful, limiting movement of the arm and shoulder may be helpful.

  2. Acute procedural pain. The frequency of painful procedures in the NICU can range from 5–15 per day. ...

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