Pain and its effects in the human neonate and fetus.

The evaluation of pain in the human fetus and neonate is difficult because pain is generally defined as a subjective phenomenon.1 Early studies of neurologic development concluded that neonatal responses to painful stimuli were decorticate in nature and that perception or localization of pain was not present.2 Furthermore, because neonates may not have memories of painful experiences, they were not thought capable of interpreting pain in a manner similar to that of adults.3"5 On a theoretical basis, it was also argued that a high threshold of painful stimuli may be adaptive in protecting infants from pain during birth.6 These traditional views have led to a widespread belief in the medical community that the human neonate or fetus may not be capable of perceiving pain.7,8 Strictly speaking, nociceptive activity, rather than pain, should be discussed with regard to the neonate, because pain is a sensation with strong emotional associations. The focus on pain perception in neonates and confusion over its differentiation from nociceptive activity and the accompanying physiologic responses have obscured the mounting evidence that nociception is important in the biology of the neonate. This is true regardless of any philosophical view on consciousness and "pain perception" in newborns. In the literature, terms relating to pain and nociception are used interchangeably; in this review, no further distinction between the two will generally be made. One result of the pervasive view of neonatal pain is that newborns are frequently not given analgesic or anesthetic agents during invasive procedures, including surgery.9-19 Despite recommendations to the contrary in textbooks on pediatric anesthesiology, the clinical practice of inducing minimal or no anesthesia in newborns, particularly if they are premature, is widespread.9-19 Unfortunately, recommendations on neonatal anesthesia are made without reference to recent data about the development of perceptual mechanisms of pain and the physiologic responses to nociceptive activity in preterm and full-term neonates. Even Robinson and Gregory's landmark paper demonstrating the safety of narcotic anesthesia in preterm neonates cites "philosophic objections" rather than any physiologic rationale as a basis for using this technique.20 Although methodologic and other issues related to the study of pain in neonates have been discussed,2123 the body of scientific evidence regarding the mechanisms and effects of nociceptive activity in newborn infants has not been addressed directly. ANATOMICAL AND FUNCTIONAL REQUIREMENTS FOR PAIN PERCEPTION The neural pathways for pain may be traced from sensory receptors in the skin to sensory areas in the cerebral cortex of newborn infants. The density of nociceptive nerve endings in the skin of newborns is similar to or greater than that in adult skin.24 Cutaneous sensory receptors appear in the perioral area of the human fetus in the 7th week of gestation; they spread to the rest of the face, the palms of the hands, and the soles of the feet by the 11th week, to the trunk and proximal parts of arms and legs by the 15th week, and to all cutaneous and mucous surfaces by the 20th week.25-26 The spread of cutaneous receptors is preceded by the development of synapses between sensory fibers and interneurons in the dorsal horn of the spinal cord, which first appear during the sixth week of gestation.27-28 Recent studies using electron microscopy and immunocytochemical methods show that the development of various types of cells in the dorsal horn (along with their laminar arrangement, synaptic interconnections, and specific neurotransmitter vesicles) begins before 13 to 14 weeks of gestation and is completed by 30 weeks.29 Lack of myelination has been proposed as an index of the lack of maturity in the neonatal nervous system30 and is used frequently to support the argument that premature or full-term neonates are not capable of pain perception. …