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Historical Development

On January 30, 1984, President Reagan spoke at the Annual Convention of Religious Broadcasters saying, “There’s another grim truth we should face up to: Medical science doctors confirm that when the lives of the unborn are snuffed out, they often feel pain, pain that is long and agonizing.”   [full remarks available here

In response to President Reagan’s statement, a prestigious group of professors, including pain specialists and two past presidents of the American College of Obstetrics and Gynecology sent the President a well-documented statement showing their strong agreement.   A copy of the letter can be viewed here

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In an early analysis (following the speech from President Reagan) titled, “Fetal Pain and Abortion: The Medical Evidence,” Vincent J. Collins, M.D., Steven R. Zielinski, M.D., and Thomas J. Marzen, Esq. wrote,

“But the presence of a functioning cortex is not necessary to pain sensation.  Even complete removal of the cortex does not eliminate the sensation of pain; no portion of the cortex, if artificially stimulated, results in pain sensation…The requisite structures for the sensation of pain are, therefore, the nociceptors, a continuous neural pathway of sensory nerves that transmit pain impulses from the nociceptor through the peripheral nervous system and the spinal cord to the thalamus, and the thalamus.  In order to determine that pain is sensed, however, these structures must not only be in place, but also known to be functioning.

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Not long after, interest in understanding and conducting medical research on fetal pain began.    Today, there are hundreds of studies which confirm the existence of fetal pain – overwhelmingly – by 20 weeks.  Now, much of the scientific focus is on treating that pain.

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With nearly 1000 scholarly articles citing to this early comprehensive pain study, the authors write,

“Various putative neurotransmitters called the tachykinins (substance P, neurokinin A, neuromedin K, and so forth) have been identified in the central nervous system, but only substance P has been investigated thoroughly and shown to have a role in the transmission and control of pain impulses. Neural elements containing substance P and its receptors appear … at 12 to 16 weeks of gestation. A high density of substance P fibers and cells have been observed in multiple areas of the fetal brain stem associated with pathways for pain perception and control and visceral reactions to pain.” [internal citations omitted]

Anand, K.J.S. & Hickey, P.R. (1987). Pain and its effects in the human neonate and fetus. New England Journal of Medicine, 317(21), 1321-1329.   Available at: http://www.cirp.org/library/pain/anand/

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Another early and persistently cited source writes,

“Endorphinergic cells have been observed in the anterior and the intermediate lobes of the fetal pituitary gland and were responsive to CRF [corticotropin-releasing factor] stimulation in vitro by 20 weeks’ gestation.”  [internal citations omitted]

Anand, K.J.S. The neuroanatomy, neurophysiology, and neurochemistry of pain, stress, and analgesia in newborns and children. Pediatr Clin North Am – 01-AUG-1989; 36(4): 795-822

**note: another recent study, Pain Assessment in Preterm Neonates, PEDIATRICS Vol. 119 No. 3 March 2007, pp. 605-607 (doi:10.1542/peds.2006-2723) by this lead author can be found at: http://pediatrics.aappublications.org/cgi/reprint/119/3/605 

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This study provides the first direct evidence that the fetus has a hormonal response to invasive stimuli.

“The rise in both β-endorphin and cortisol concentrations during transfusion (median increase 590% and 183% respectively) was greater than observed in preterm neonates undergoing surgery under light anaesthasia (approximately 80% and 105% respectively)….Just as physicians now provide neonates with adequate analgesia, our findings suggest that those dealing with the fetus should consider making similar modifications to their practice. [internal citations omitted]

Giannakoulopoulos, X., Sepelveda, W., Kourtis, P., Glover, V.,& Fisk, N. (1994). Fetal plasma cortisol and β-endorphin response to intrauterine needling. Lancet, 77-81.

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This study provides early insight into the flawed assumptions on pain.

“Because self-report may be absent or a faulty source of inference, nonverbal behavioral information is often needed and used for pain assessment.” The study also says, “Such evidence [behavioral response associated with painful stimuli] suggests that the sensation of pain requires no prior experience, and appears early in ontogeny in order to serve as a signaling system for tissue damage. Human fetuses mounted hormonal responses to painful stimuli delivered in utero, which were similar to the hormonal responses of preterm neonate or older children experiencing such stimuli.”

K.J.S. Anand & Kenneth D. Craig, Editorial: New Perspectives on the Definition of Pain, 67 Pain 3 (1996)

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Some say the fetus may experience more pain than neonate counterparts.

“The last pathways in the nociceptive system to be formed are the inhibitory descending serotonin neurones, which can block the ascending pathways. These do not form until after birth, raising the possibility that the fetus may actually be more sensitive to noxious stimuli than the older child….” [internal citations omitted]

Glover and Fisk, Fetal pain: implications for research and practice, British Journal of Obstetrics and Gynaecology; September 1999, Vol106, pp. 881-886.  Available at: http://onlinelibrary.wiley.com/doi/10.1111/j.1471-0528.1999.tb08424.x/pdf

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This study pointed to evidence of the stress response

“Invasive diagnostic and therapeutic techniques are increasingly applied to the fetus. It is not known if the fetus feels pain during such procedures, but the fetus does mount significant stress hormonal and circulatory changes in response to these from 18–20 weeks. Perinatal stress may have long-term neurodevelopmental implications.”

Smith et. al. Pain and stress in the human fetus; European Journal of Obstetrics & Gynecology and Reproductive Biology, Volume 92, Issue 1, September 2000, Pages 161-165.

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This landmark study provided further evidence of, and recommended treatment for the stress response.

“Our group has shown that the human fetus from 18–20 weeks elaborates pituitary-adrenal, sympatho-adrenal, and circulatory stress responses to physical insults.” P 828 “This study provides the first evidence that direct fetal analgesia reduces stress responses to intervention inutero. Further experiments are now indicated using higher-dose fentanyl, as well as studies using different drugs and different modes of administration. [internal citations omitted]

NM Fisk, R Gitau, Effect of Direct Fetal Opioid Analgesia on Fetal Hormonal and Hemodynamic Stress Response to Intrauterine Needling; Anesthesiology 2001; 95:828–35

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More evidence:

“The first neurons to link the cortex with the rest of the brain are in place from about 16 weeks’ gestation. Their activation could be associated with unpleasant conscious experience, even if not pain. Thalamic fibers first penetrate the subplate zone at about 17 weeks gestation and the cortex at 20 weeks. These issues are important, not only because of immediate suffering, but also because of possible long term adverse effects of this early experience.”

Glover, Vivette The fetus may feel pain from 20 weeks; The Fetal Pain Controversy. Conscience Pg. 35(3) Vol. 25 No. 3 ISSN: 0740-6835

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With the fetal stress response fully accepted, attention turned to more efficiently treating it.

“In contrast to DZP, REMI has the potential, as do other opioids, to provide effective fetal analgesia after accidental direct stimulation (e.g., touching with endoscopes). Therefore, it has been suggested that pain relief has to be provided during in utero interventions on the fetus from mid-gestation (20 weeks) on. Direct administration of fentanyl to the human fetus has been shown to block the fetal stress response during mid-gestational in utero interventions. In our trial inadvertent touching of an immobilized fetus resulted in fetal “awakening.” Therefore, when fetal analgesia or blunting of the fetal stress response is required, additional drugs (opioids and nondepolarizing muscle relaxants) must be administered directly to the fetus.” [internal citations omitted]

Van de Velde M, Van Schoubroeck D, Lewi LE, et al. Remifentanil for fetal
immobilization and maternal sedation during fetoscopic surgery: a randomized,
double-blind comparison with diazepam. Anesth Analg 2005;101:251–8.

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This study presented first-hand testimony of behavioral responses.

“One account: ‘Midwife, 9: But when it comes to fetal pain, I don’t know—I really don’t know and I think it’s all very unclear, but I would say it’s 21 weeks—whether we say it’s before that I don’t know. Do they [fetuses] know what pain is to be able to perceive it as pain? But certainly, they react to having a needle stuck in their chest and their heart stopped with a drug.’ Another account:  ’Gynaecologist, 22:After 18 weeks if I do a feticide, I put a needle in the baby’s heart – I’m not sure it’s necessary, but I do it I suppose as a sort of PR exercise, because I think it’s important to be seen to be caring about the fetus if you see what I mean.. so I feel I need to do it, it’s the politics of caring about the Fetus.’”

C. Williams; Framing the fetus in medical work: rituals and practices; Social Science & Medicine. 60 (2005) 2085–2095

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This study criticized a JAMA study that placed fetal pain in the third trimester.

“Closer examination reveals three major flaws in the scientific rationale of recent reviews purporting to rule out the occurrence of fetal pain. First, pain perception is presented as mediated by a hard-wired system, passively transmitting nociceptive impulses until “perception” occurs in the somatosensory cortex. Pain research over the past 40 years, beginning with the gate control theory and extended through vast amounts of clinical and experimental data, has long outgrown this Cartesian view of pain. Based upon this progress, we can assert with confidence that nociceptive signaling in prenatal development depends not only on the context and characteristics of the stimulus, but also on the fetal behavioral state at that time. For example, fetuses undergoing intrauterine invasive procedures were reported to show coordinated responses promoting the avoidance of tissue injury. Second, reviewers of this literature incorrectly assume that pain perception during fetal life must engage the same neural structures as those used by adults. Lack of development of the latter areas is then used to support the argument that fetuses do not feel pain until late gestation. Clinical and animal research shows that the fetus or neonate is not a “little adult,” that the structures used for pain processing in early development are unique and different from those of adults, and that many of these fetal structures and mechanisms are not maintained beyond specific periods of early development. The immature pain system thus uses the neural elements available during each stage of development to carry out its signaling role. Third, such reviews presuppose that cortical activation is necessary for fetal pain perception. Based upon this assumption, the lack of evidence for pain-specific thalamocortical connections supports their contention against fetal pain. This line of reasoning, however, ignores clinical data cited above that ablation or stimulation of the primary somatosensory cortex does not alter pain perception in adults, whereas thalamic ablation or stimulation does. The thalamus plays a pivotal role in regulating the spinal-brainstem-spinal loops that mediate context-dependent descending facilitation or inhibition, coordinated via the key mechanisms underlying consciousness.” [ internal citations omitted]

Clancy et. Al. Fetal Pain? Clinical Updates. Pain. Volume XIV, No. 2 June 2006.

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This study writes that while “evidence for conscious pain perception is indirect, evidence for the subconscious incorporation of pain into neurological development and plasticity is incontrovertible.” Expanded finding are below.

“ 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.”

Lowrey, et al. Neurodevelopmental Changes of Fetal Pain. Seminars in Perinatology.
Volume 31, Issue 5, October 2007, Pages 275-282.

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This study was hugely influential, but more as challenging those who require later gestation consciousness before they will call it or treat “pain.”

“The tacit consensus concerning the cerebral cortex as the ‘organ of consciousness,’ ” Merker wrote, may “have been reached prematurely, and may in fact be seriously in error.”

Merker, Consciousness without a cerebral cortex: A challenge for Neuroscience and medicine; Behavioral and Brain Sciences. (2007) 30, 63–134  available at:  http://www.willamette.edu/~levenick/cs448/Merker.pdf

o In response to this study titled, Consciousness, cortical function, and pain
perception in nonverbal humans; K. J. S. Anand, the author writes,

“Within the medical/scientific community, concepts of pain are based on its semantic definition rather than the actual experience it signifies. Pain is defined by Merskey and Bogduk (1994) as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage,” followed by the note that, “Pain is always subjective. Each individual learns the application of the word through Commentary/Merker: Consciousness without a cerebral cortex experiences related to injury in early life” (Merskey & Bogduk 1994). Over the years, this definition has propagated undue credibility for the verbal expression of pain, defined within the context of adult consciousness, engendering medical practices that regard verbal self-report as the “gold standard” for pain (K. D. Craig 1997; Cunningham 1998; 1999). Major flaws in this definition include its excessive reliance on verbal self report, the criterion that some form of learning is required in order to experience pain, and its focus on use of this word rather than the experience of pain (Anand & Craig 1996; Anand et al. 1999; K. D. Craig 1997; Shapiro 1999;Wall 1997).”

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This recent study highlights the forming consensus.

“There is considerable evidence that the fetus may experience pain. Not only is there a moral obligation to provide fetal anaesthesia and analgesia, but it has also been shown that pain and stress may affect fetal survival and neurodevelopment.”

Gupta et al. Fetal surgery and anaesthetic implications Contin Educ Anaesth Crit Care Pain.2008; 8: 71-75 Continuing Education in Anaesthesia, Critical Care & Pain 2008 8(2):71-75; doi:10.1093/bjaceaccp/mkn004