Neurodevelopmental Changes of Fetal Pain

doi:10.1053/j.semperi.2007.07.004

Seminars in Perinatology

Volume 31, Issue 5, October 2007, Pages 275-282

https://doi.org/10.1053/j.semperi.2007.07.004 Get rights and content

Pain in the developing fetus is controversial because of the difficulty in measuring and interpreting pain during gestation. It has received increased attention lately because of recently introduced legislation that would require consideration of fetal pain during intentional termination of pregnancy. During development, sensory fibers are abundant by 20 weeks; a functional spinal reflex is present by 19 weeks; connections to the thalamus are present by 20 weeks; and connections to subplate neurons are present by 17 weeks with intensive differentiation by 25 weeks. These cells are important developmentally, but decline as a result of natural apoptosis. Mature thalamocortical projections are not present until 29 to 30 weeks, which has led many to believe the fetus does not experience emotional “pain” until then. Pain requires both nociception and emotional reaction or interpretation. Nociception causes physiologic stress, which in turn causes increases in catecholamines, cortisol, and other stress hormones. Physiological stress is different from the emotional pain felt by the more mature fetus or infant, and this stress is mitigated by pain medication such as opiates. The plasticity of the developing brain makes it vulnerable to the stressors that cause long-term developmental changes, ultimately leading to adverse neurological outcomes. Whereas evidence for conscious pain perception is indirect, evidence for the subconscious incorporation of pain into neurological development and plasticity is incontrovertible. Scientific data, not religious or political conviction, should guide the desperately needed research in this field. In the meantime, it seems prudent to avoid pain during gestation.

Section snippets

Background: The Abortion Controversy

Primarily because of controversy regarding pain relief to the human fetus during abortion, there has been renewed interest in fetal pain. Two recent reviews on fetal pain have argued against providing fetal pain relief during abortion, and they argue that insufficient scientific evidence supports such legislation.6, 7 One review concluded that pain perception is unlikely before 29 to 30 weeks of human gestation.⁶ Unfortunately, many of the patients who require neonatal intensive care are born

Other Neurodevelopmental Considerations

Pain perception requires two distinctly different components: 1) nociception the sensation of the stimuli and 2) perception with emotional reaction which is the unpleasant feeling that occurs in reaction to the noxious stimuli. These distinct components are processed by the brain in areas anatomically and physiologically distinct from one another (see Fig. 1).60, 61, 62 Human development occurs as an analog rather than digital process. The neurodevelopment milestones, as defined, are strictly

Conclusion

For adults, pain is an emotional experience. We define pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.” We should keep in mind that the noxious stress response that activates the hypothalamic pituitary and adrenal axis is linked to the emotional pain response. Activation of the hypothalamic pituitary adrenal axis can occur in the absence of cortical activation, and fetuses have exhibited this

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Pain is a complex phenomenon that involves more than a simple physical response to external stimuli. In maternal-fetal surgical procedures, fetal analgesia is used primarily to blunt fetal autonomic responses and minimize fetal movement. The purpose of this Consult is to review the literature on what is known about the potential for fetal awareness of pain and to discuss the indications for and the risk-benefit calculus involved in the use of fetal anesthesia and analgesia. The recommendations by the Society for Maternal-Fetal Medicine are as follows: (1) we suggest that fetal paralytic agents be considered in the setting of intrauterine transfusion, if needed, for the purpose of decreasing fetal movement (GRADE 2C); (2) although the fetus is unable to experience pain at the gestational age when procedures are typically performed, we suggest that opioid analgesia should be administered to the fetus during invasive fetal surgical procedures to attenuate acute autonomic responses that may be deleterious, avoid long-term consequences of nociception and physiological stress on the fetus, and decrease fetal movement to enable the safe execution of procedures (GRADE 2C); and (3) due to maternal risk and a lack of evidence supporting benefit to the fetus, we recommend against the administration of fetal analgesia at the time of pregnancy termination (GRADE 1C).
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Pain is a complex phenomenon that involves more than a simple physical response to external stimuli. In maternal-fetal surgical procedures, fetal analgesia is used primarily to blunt fetal autonomic responses and minimize fetal movement. The purpose of this Consult is to review the literature on what is known about the potential for fetal awareness of pain and to discuss the indications for and the risk-benefit calculus involved in the use of fetal anesthesia and analgesia. The recommendations by the Society for Maternal-Fetal Medicine are as follows: (1) we suggest that fetal paralytic agents be considered in the setting of intrauterine transfusion, if needed, for the purpose of decreasing fetal movement (GRADE 2C); (2) although the fetus is unable to experience pain at the gestational age when procedures are typically performed, we suggest that opioid analgesia should be administered to the fetus during invasive fetal surgical procedures to attenuate acute autonomic responses that may be deleterious, avoid long-term consequences of nociception and physiological stress on the fetus, and decrease fetal movement to enable the safe execution of procedures (GRADE 2C); and (3) due to maternal risk and a lack of evidence supporting benefit to the fetus, we recommend against the administration of fetal analgesia at the time of pregnancy termination (GRADE 1C).
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Les réflexes archaïques, qui émergent pour la plupart in utero, ont de multiples fonctions. Indispensables à la survie du fœtus puis du nouveau-né dès les premières minutes de vie, ils sont également fortement impliqués dans le développement moteur, sensoriel et émotionnel de l’enfant.
Archaic reflexes, most of which emerge in utero, have multiple functions. Indispensable for the survival of the foetus and then the newborn from the first minutes of life, they are also strongly involved in the motor, sensory and emotional development of the child.
Conceptualizing Pain and Personhood in the Periviable Period: Perspectives from Reproductive Health and Neonatal Intensive Care Unit Clinicians
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In 2020, the Pain Capable Unborn Child Protection Act was brought to an unsuccessful Senate vote for the third time in five years. The Act seeks to prohibit abortions after 20 weeks post-conception based on the scientifically contested claim that fetuses are at that point capable of feeling pain. It thus seeks to undermine Roe v. Wade's viability standard by asserting that the capacity for pain perception is sufficient for “compelling governmental interest” in fetal life. The ability of many NICUs to offer life-sustaining interventions for periviable neonates means that, in many states, neonatologists and physicians who provide second-trimester abortion care may manage cases of the same gestational age. Given this overlap, this qualitative study examines how clinicians think about the capacity of periviable entities to feel pain and how these ideas shape clinical practice and understandings of compassionate care. Drawing on twenty semi-structured interviews conducted between June 2019 and April 2020 with clinicians providing second-trimester abortion care and NICU care in the Northeast United States, it examines how pain is “known” in the periviable period and how clinicians think about pain in relationship to personhood. A key finding is that the meaning of pain and implications for clinical care is shaped by the anticipated futures and personhood status of periviable entities as determined by pregnant people and families of neonates. Clinicians also stated that concerns around the alleviation of suffering, defined as long-term or chronic distress for pregnant people and/or neonates and their families, were more pressing than the potential experience of short-term physical pain. Legislative attempts to make contested ideas of “fetal pain” the basis for “governmental interest” ignores other forms of suffering that might result from denial of options, and potentially places clinicians at odds with their own conceptions of competent and compassionate care.
Local injury and systemic infection in infants alter later nociception and pain affect during early life and adulthood
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Newborns in intensive care are regularly exposed to minor painful procedures at developmental time points when noxious stimulation would be normally absent. Pain from these interventions is inconsistently treated and often exists concurrently with systemic infection, a common comorbidity of prematurity. Our understanding of the independent and combined effects of early painful experiences and infection on pain response is incomplete. The main goals of this research therefore were to understand how pain and infection experienced early in life influence future nociceptive and affective responses to painful stimuli. Rat pups were infected with E-coli on postnatal day 2 (PN2) and had left hind paw injury with carrageenan on PN3. Standard thermal tests for acute pain, formalin tests for inflammatory pain, and conditioned place aversion testing were performed at different ages to assess the nociceptive and affective components of the pain response. Early E-coli infection and early inflammatory injury with carrageenan both independently increased pain scores following hind paw reinjury with formalin on PN8, with effects persisting into adulthood in the carrageenan exposed group. When experienced concurrently, early E-coli infection and carrageenan exposure also increased conditioned aversion to pain in adults. Effect of sex was significant only in formalin testing, with males showing higher pain scores in infancy and females showing higher pain scores as adults. These findings demonstrate that infection experienced early in life can alter both the nociceptive and affective components of the pain response and that there is a cumulative effect of local and systemic pro-inflammatory processes on the aversive component of pain.
5.26 - The Development of the Nociceptive System and Childhood Pain
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Childhood covers an extensive developmental period from preterm birth to late adolescence. Nociceptive mechanisms vary with age, and we provide an overview of the development of peripheral and central nociceptive mechanisms, and the maturation of the anatomical framework that mediates brain nociceptive mechanisms. As the mechanisms, sources, and impact of acute and chronic pain vary with age and developmental stage, we use post-operative pain and neuropathic pain to illustrate aspects of the assessment and management of acute and chronic pain in children. Use of specialized neurophysiological and neuroimaging techniques, including current data related to age- and sex-dependent differences are summarized.

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Neurodevelopmental Changes of Fetal Pain

Section snippets

Background: The Abortion Controversy

Other Neurodevelopmental Considerations

Conclusion

Crit Care Nurs Clin North Am

Physiol Behav

Br J Anaesth

Pain

Soc Sci Med

Pain Forum

Neuroimage

Pain

Pain

Exp Neurol

Neuroscience

Exp Neurol

Semin Pediatr Neurol

Neurosci Lett

Behav Brain Res

Pediatr Clin North Am

Brain Dev

Lancet

J Pediatr

Lancet

Lancet

Logic, truth and language in concepts of pain

Qual Life Res

Can adverse neonatal experiences alter brain development and subsequent behavior?

Biol Neonate

Pain and its effects in the human neonate and fetus

N Engl J Med

Fetal pain: a systematic multidisciplinary review of the evidence

JAMA

Can fetuses feel pain?

Br Med J

Pain mechanisms: a new theory

Science

Testing the gate-control theory of pain in man

J Neurol Neurosurg Psychiatry

Neuronal plasticity: increasing the gain in pain

Science

Psychological and neural mechanisms of the affective dimension of pain

Science

Early language development and its neural correlates

The development of nociceptive circuits

Nat Rev Neurosci

Developmental neurobiology of pain in neonatal rats

Lab Animal

We don't know: better to err on the safe side from mid-gestation

Br Med J

A new view of pain as a homeostatic emotion

Trends Neurosci

Interoception: the sense of the physiological condition of the body

Curr Opin Neurobiol

Pain mechanisms: labeled lines versus convergence in central processing

Annu Rev Neurosci

Thalamic axons confer a blueprint of the sensory periphery onto the developing rat somatosensory cortex

Brain Res Dev Brain Res