Emotions

"Most pain researchers adopt a definition of pain that emphasises the sensory, cognitive and affective response to a noxious event. This understanding of pain is supported by the International Association of Pain (IASP) which defines pain as ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage,or described in terms of such damage...pain is always subjective. Each individual learns the application of the word through experiences related to injury in early life’.1 By this definition, pain does not have primacy over subjectivity, existing before and in addition to subjectivity, but is experienced through subjectivity. It suggests that pain is a part of knowledge and requires the existence of a conceptual apparatus that can marshal all its dimensions into a coherent experience. Although there is considerable merit in the IASP definition of pain, it does tend towards a view of pain as being a constituent part of higher cognitive function. There is disquiet in denying a rawer, more primitive, form of pain or suffering that the fetus, neonate and many animals might experience.2–4 One possible solution is to recognise that the newborn infant might be said to feel pain, whereas only the older infant can experience that they are in pain and explicitly share their condition with others as an acknowledged fact of being.5 Currently there is no immediately obvious way of resolving these arguments empirically. It is possible, however, to argue that even a raw sense of pain involves more than reflex activity and will, therefore, require the higher regions of the cortex to be connected and functional. The age when this minimum requirement is fulfilled is explored in the rest of this chapter."

"The neural regions and pathways that are responsible for pain experience remain under debate but it is generally accepted that pain from physical trauma requires an intact pathway from the periphery, through the spinal cord, into the thalamus and on to regions of the cerebral cortex including the primary sensory cortex (S1), the insular cortex and the anterior cingulated cortex. Fetal pain is not possible before these necessary neural pathways and structures (figure 1) have developed."

"For the fetus to respond to surgical damage, receptors in the affected tissue, such as skin and muscle, must signal the noxious stimulus or damage to the central nervous system. Nociceptors are sensory nerve terminals found in the skin and internal organs that convert tissue damage into electrical signals. The pattern and strength of these nociceptor signals is the first determining step in generating pain. If nociceptor activity is prevented, such as following local anaesthesia, then pain is blocked. Deep tissue damage, for example, that cuts through nerve bundles causes a brief burst of electrical activity in some of the cut nerve endings known as an injury discharge. The injured tissue, however, is now isolated from the central nervous system and, within a few minutes, the isolated tissue becomes ‘numb’ and pain free. Similarly, rare genetic defects that prevent all nociceptive signals result in a complete inability to sense pain. Anatomical studies of human fetal skin shows the presence of nerve terminals and fibres deep in the skin from 6 weeks of gestational age. These terminals are not nociceptors and are specialised for the processing of non-damaging sensations such as touch, vibration and temperature, rather than pain. From 10 weeks, nerve terminals become more numerous and extend towards the outer surface of the skin. The terminals closer to the surface are likely to be immature nociceptors, necessary for pain experience following tissue damage, but they are not unequivocally present until 17 weeks. In other mammals, newly formed fetal nociceptors are able to signal tissue damage but the intensity of their signals is weaker than in adults. The internal organs develop nerve terminals later than the skin, beginning to appear from 13 weeks and then increasing and spreading with age, so that the pancreas, for example, is innervated by 20 weeks."

"Specialised nerve terminals, nociceptors, are likely to detect surgical tissue damage from early in fetal life (around 10 weeks for the skin and 13 weeks for the internal organs). These nociceptors gradually mature over the next 6–8 weeks and the strength of their signals increases over fetal life. The presence of nociceptors is necessary for perception of acute surgical pain and so pain is clearly not possible before the nociceptors first appear at 10 weeks. The presence of nociceptors alone, however, is not a sufficient condition for pain experience. The electrical activity that is generated at nociceptor terminals by tissue damage must also be conducted along nerve fibres from the skin and into the spinal cord and brain. It is only when the brain receives information about the damage that the fetus can have any potential of awareness of it."

"We begin by considering the scientific evidence for the presence of specific anatomical and physiological connections in the brain that are responsible for signalling noxious events to the central nervous system. Noxious stimuli are those that damage the tissues of the body or threaten to do so, such as surgical incision or physical trauma of the skin. In this context, we define pain as ‘the unpleasant sensory or emotional response to such tissue damage’ and trace the development of those responses through fetal development. We follow the path of the signals produced by tissue damage at sensory detectors in the skin and other organs, through to sensory circuits in the spinal cord, brainstem and thalamus and finally to the cerebral cortex, the site of higher level sensory processing. At each stage, we consider the scientific evidence for functional development and how this evidence may be interpreted. This section includes details derived from over 50 papers identified as relevant. Most were published since the last Working Party report1 but this current report also considers the older material included in the previous report. In addition to understanding the anatomical and physiological connections, it is also important to consider the psychological aspects of pain. Broadly accepted definitions of pain refer to pain as a subjective experience involving cognition, sensation and affective processes. These psychological concepts are inevitably harder to address in a fetus but should not be ignored."

"Before any information about a noxious or tissue damaging stimulus can reach the brain, it has to be transmitted through the spinal cord (for the body) or the brainstem (for the head and neck). This transmission requires the growth of nerve fibres from the skin to the spinal cord or brainstem and then further growth of nerve fibres along the spinal cord or brainstem and into the brain. Staining of postmortem tissue reveals that nerve fibres grow into the fetal spinal cord from 8 weeks. These fibres, however, are specialised for the control of movement and some aspects of touching or prodding the body or positioning a limb. The growth of nerve fibres connecting nociceptive terminals to the spinal cord lags behind that of other sensory inputs in non-human mammals. Similar connections in the human are also likely to lag but the specific timings remain unknown. Preliminary studies have failed to demonstrate nerve fibres from nociceptive terminals in the fetal post-mortem spinal cord before 19 weeks."

"Fetal behavioural responses have also been used as indicators of stress or pain. Shortly after the development of skin sensitivity, around 10 weeks, repeated stimulation results in hyperexcitability and a generalised movement of all limbs. After 26 weeks, this generalized movement gradually gives way to more coordinated behavioural responses that indicate improved organisation within the nervous system. Infants delivered at 26–31 weeks, for example, show coordinated facial expressions in response to heel prick, although these are immature compared to older infants. Four-D images of the fetus have also been reported to show fetuses ‘scratching’, ‘smiling’, ‘crying’ and ‘sucking’ at 26 weeks of gestational age. Although these later behavioural responses are not spinal cord reflexes, the responses are still unlikely to involve higher cortical centres. An anencephalic fetus withdraws from noxious stimulation, demonstrating that this response is mediated at a subcortical level. Similarly, infants with significant neonatal neurological injury due to a parenchymal brain injury respond to noxious stimulation with a pattern of behavioural reactions similar to infants without brain injury."

"The experience of pain needs cognitive, sensory, and affective components, as well as the necessary anatomical and physiological neural connections. Nociceptors first appear at 10 weeks of gestation in the fetus but they are not sufficient for the experience of pain in themselves. That requires that electrical activity is conducted from the receptors into the spinal cord and to the brain. Fibers to nociceptor terminals in the spinal cord have not been demonstrated before 19 weeks of gestation, although it is known that the fetus withdraws from a needle and may exhibit a stress response from about 18 weeks. At this stage, it is apparent that activity in the spinal cord, brain stem and mid-brain structures are sufficient to generate reflex and humoral responses but not sufficient to support pain awareness. At the same time, completion of the major neural pathways from the periphery to the cortex, at around 24 weeks of gestation, heralds the beginning of further neuronal maturation. The proliferation of cortical neurons and synaptic contacts begins prenatally but continues postnatally. Magnetic imaging techniques have recorded fetal auditory and visual responses from 28 weeks but it has not been possible to record directly when cortical neurons first begin to respond to tissue damaging inputs, although there is evidence of neural activity in primary sensory cortex in premature infants (around 24 weeks). It has been suggested that subcortical regions can organise responses to noxious stimuli and provide for the pain experience complete within itself but there is no evidence (or rationale) that the subcortical and transient brain regions support mature function. Thus, although the cortex can process sensory input from 24 weeks, it does not mean that the fetus is aware of pain. There is sound evidence for claiming the cortex is necessary for pain experience but this is not to say that it is sufficient."

"Following concerns generated by the debate on fetal awareness and, particularly, the controversy around whether the fetus could feel pain, the RCOG published, in October 1997, a working party report. A guiding principle in that report was concern that the fetus should be protected from any potentially harmful or painful procedure but, at the same time, the assessment of the capacity to be harmed should be based on established scientific evidence. A major and important conclusion of the report was that the human fetus did not have the necessary structural integration of the nervous system to experience awareness or pain before 26 weeks of gestation. In addition, the report recommended that those carrying out diagnostic or therapeutic procedures on the fetus in utero at or after 24 weeks should consider the need for fetal analgesia. This guidance was welcomed by the clinical and scientific communities, although, in recent years, the report has from time to time come under criticism in some quarters for being out of date and perhaps not having assessed all the known scientific evidence. This criticism has been most evident in discussing the age of viability (at present taken as 24 weeks of gestation in the UK) and the upper gestational limit in the context of induced abortion. The House of Commons Science and Technology Committee, in its report on Scientific Developments Relating to the Abortion Act 1967 (published in October 2007), made a number of important conclusions and recommendations, including some of direct relevance to this issue: ‘We conclude that, while the evidence suggests that foetuses have physiological reactions to noxious stimuli, it does not indicate that pain is consciously felt, especially not below the current upper gestational limit of abortion. We further conclude that these factors may be relevant to clinical practice but do not appear to be relevant to the question of abortion’. A minority report, however, recorded in the minutes of the Committee on 29 October 2007 said, ‘We are deeply concerned that the RCOG failed to give full information to the House of Commons Select Committee...since 1997 the RCOG has consistently denied that foetuses can feel pain earlier than 26 weeks, without acknowledging that amongst experts in this field there is no consensus. Professor Anand is a world authority in the management of neonatal pain and has put forward a cogent argument suggesting that the RCOG position is based on a number of false or uncertain presuppositions’. In the Government response to the House of Commons report (released November 2007) the Minister of State for Health welcomed the report and its conclusions and recommendations but importantly also indicated that ‘we note the Committee’s findings and are in agreement that the consensus of scientific evidence with regard to fetal pain at gestations below 26 weeks and we will be commissioning the College to review their 1997 working party report into fetal pain which will re-examine the latest evidence, much of which has been considered by the Committee, and any new research currently underway’."

"In the push to pass fetal-pain legislation, Anand’s name has been invoked at every turn; he has become a favorite expert of the anti-abortion movement precisely because of his credentials. “This Oxford- and Harvard-trained neonatal pediatrician had some jarring testimony about the subject of fetal pain,” announced the Republican congressman Mike Pence to the House of Representatives in 2004, “and it is truly made more astonishing when one considers the fact that Dr. Anand is not a stereotypical Bible-thumping pro-lifer.” Anand maintains that doctors performing abortions at 20 weeks or later should take steps to prevent or relieve fetal pain. But it is clear that many of the anti-abortion activists who quote him have something more sweeping in mind: changing perceptions of the fetus. In several states, for example, information about fetal pain is provided to all women seeking abortions, including those whose fetuses are so immature that there is no evidence of the existence of even a stress response. “By personifying the fetus, they’re trying to steer the woman’s decision away from abortion,” says Elizabeth Nash, a public-policy associate at the Guttmacher Institute, a reproductive-rights group."

"In his speeches about fetal pain, Senator Brownback often asks why a fetus undergoing surgery receives anesthesia but not a fetus “who is undergoing the life-terminating surgery of an abortion.” Mark Rosen rejects the analogy. “Fetal surgery is a different circumstance than abortion,” he says, pointing out that none of the objectives of anesthesia for fetal surgery — relaxing the uterus, for example — apply to the termination of pregnancy. That includes an objective identified just recently: preventing possible long-term damage. For the fetus that is to be aborted, there is no long term. And if there is no pain, as Rosen maintains, then there is no cause to put the woman’s health at risk."

"In their use of pain to make the fetus seem more fully human, anti-abortion forces draw on a deep tradition. Pain has long played a special role in how society determines who is like us or not like us (“us” being those with the power to make and enforce such distinctions). The capacity to feel pain has often been put forth as proof of a common humanity. Think of Shylock’s monologue in “The Merchant of Venice”: Are not Jews “hurt with the same weapons” as Christians, he demands. “If you prick us, do we not bleed?” Likewise, a presumed insensitivity to pain has been used to exclude some from humanity’s privileges and protections. Many 19th-century doctors believed blacks were indifferent to pain and performed surgery on them without even that era’s rudimentary anesthesia. Over time, the charmed circle of those considered alive to pain, and therefore fully human, has widened to include members of other religions and races, the poor, the criminal, the mentally ill — and, thanks to the work of Sunny Anand and others, the very young. Should the circle enlarge once more, to admit those not yet born? Should fetuses be added to what Martin Pernick, a historian of the use of anesthesia, has called “the great chain of feeling”? Anand maintains that they should."

"BUT THE QUESTION of fetal pain is not irrelevant when applied to abortion. On April 4, 2004, Sunny Anand took the stand in a courtroom in Lincoln, Neb., to testify as an expert witness in the case of Carhart v. Ashcroft. This was one of three federal trials held to determine the constitutionality of the ban on a procedure called intact dilation and extraction by doctors and partial-birth abortion by anti-abortion groups. Anand was asked whether a fetus would feel pain during such a procedure. “If the fetus is beyond 20 weeks of gestation, I would assume that there will be pain caused to the fetus,” he said. “And I believe it will be severe and excruciating pain.” After listening to Anand’s testimony and that of doctors opposing the law, Judge Richard G. Kopf declared in his opinion that it was impossible for him to decide whether a “fetus suffers pain as humans suffer pain.” He ruled the law unconstitutional on other grounds. But the ban was ultimately upheld by the U.S. Supreme Court, and Anand’s statements, which he repeated at the two other trials, helped clear the way for legislation aimed specifically at fetal pain. The following month, Sam Brownback, Republican of Kansas, presented to the Senate the Unborn Child Pain Awareness Act, requiring doctors to tell women seeking abortions at 20 weeks or later that their fetuses can feel pain and to offer anesthesia “administered directly to the pain-capable unborn child.” The bill did not pass, but Brownback continues to introduce it each year. Anand’s testimony also inspired efforts at the state level. Over the past two years, similar bills have been introduced in 25 states, and in 5 — Arkansas, Georgia, Louisiana, Minnesota and Oklahoma — they have become law. In addition, state-issued abortion-counseling materials in Alaska, South Dakota and Texas now make mention of fetal pain."

"When it comes to the way adults feel pain, science has borne out the optimistic belief that we are all the same under the skin. As research is now revealing, the same may not be true for fetuses; even Anand calls the fetus “a unique organism.” Exhibiting his flair for the startling but apt expression, Stuart Derbyshire warns against “anthropomorphizing” the fetus, investing it with human qualities it has yet to develop. To do so, he suggests, would subtract some measure of our own humanity. And to concern ourselves only with the welfare of the fetus is to neglect the humanity of the pregnant woman, Mark Rosen notes. When considering whether to provide fetal anesthesia during an abortion, he says, it’s not “erring on the safe side” to endanger a woman’s health in order to prevent fetal pain that may not exist. Indeed, the question remains just how far we would take the notion that the fetus is entitled to protection from pain. Would we be willing, for example, to supply a continuous flow of drugs to a fetus that is found to have a painful medical condition? For that matter, what about the pain of being born? Two years ago, a Swiftian satire of the Unborn Child Pain Awareness Act appeared on the progressive Web site AlterNet.org. Written by Lynn Paltrow, the executive director of the National Advocates for Pregnant Women, it urged the bill’s authors to extend its provisions to those fetuses “subjected to repeated, violent maternal uterine contraction and then forced through the unimaginably narrow vaginal canal.”"

"Recent research provides a potentially urgent reason to ask this question. It shows that pain may leave a lasting, even lifelong, imprint on the developing nervous system. For adults, pain is usually a passing sensation, to be waited out or medicated away. Infants, and perhaps fetuses, may do something different with pain: some research suggests they take it into their bodies, making it part of their fast-branching neural networks, part of their flesh and blood. Anna Taddio, a pain specialist at the Hospital for Sick Children in Toronto, noticed more than a decade ago that the male infants she treated seemed more sensitive to pain than their female counterparts. This discrepancy, she reasoned, could be due to sex hormones, to anatomical differences — or to a painful event experienced by many boys: circumcision. In a study of 87 baby boys, Taddio found that those who had been circumcised soon after birth reacted more strongly and cried for longer than uncircumcised boys when they received a vaccination shot four to six months later. Among the circumcised boys, those who had received an analgesic cream at the time of the surgery cried less while getting the immunization than those circumcised without pain relief. Taddio concluded that a single painful event could produce effects lasting for months, and perhaps much longer. “When we do something to a baby that is not an expected part of its normal development, especially at a very early stage, we may actually change the way the nervous system is wired,” she says. Early encounters with pain may alter the threshold at which pain is felt later on, making a child hypersensitive to pain — or, alternatively, dangerously indifferent to it. Lasting effects might also include emotional and behavioral problems like anxiety and depression, even learning disabilities (though these findings are far more tentative). Do such long-term effects apply to fetuses? They may well, especially since pain experienced in the womb would be even more anomalous than pain encountered soon after birth. Moreover, the ability to feel pain may not need to be present in order for “noxious stimulation” — like a surgeon’s incision — to do harm to the fetal nervous system. This possibility has led some to venture an early end to the debate over fetal pain. Marc Van de Velde, an anesthesiologist and pain expert at University Hospitals Gasthuisberg in Leuven, Belgium, says: “We know that the fetus experiences a stress reaction, and we know that this stress reaction may have long-term consequences — so we need to treat the reaction as well as we can. Whether or not we call it pain is, to me, irrelevant.”"

"Sunny days wouldn't be special if it wasn't for rain; joy wouldn't feel so good if it wasn't for pain."

"Following concerns generated by the debate on fetal awareness and, particularly, the controversy around whether the fetus could feel pain, the RCOG published, in October 1997, a working party report.1 A guiding principle in that report was concern that the fetus should be protected from any potentially harmful or painful procedure but, at the same time, the assessment of the capacity to be harmed should be based on established scientific evidence. A major and important conclusion of the report was that the human fetus did not have the necessary structural integration of the nervous system to experience awareness or pain before 26 weeks of gestation. In addition, the report recommended that those carrying out diagnostic or therapeutic procedures on the fetus in utero at or after 24 weeks should consider the need for fetal analgesia."

"[N]one of us has any memory of the pain of being born, which is not to say that birth, from the fetus’ point aaof view, could not still have been a painful process."

"Pain is universal. We all experience pain, loss, and death the same way"

"The sword of time will pierce our skin It doesn't hurt when it begins But as it works its way on in The pain grows stronger watch I bring That suicide is painless It brings so many changes And I can take or leave them if I please."

"[B]ecause of possible risks and difficulties in administration, fetal analgesia should not be employed where the only consideration is concern about fetal awareness or pain. Similarly, there appeared to be no clear benefit in considering the need for fetal analgesia prior to termination of pregnancy, even after 24 weeks, in cases of fetal abnormality. However, this did not obviate the need to consider feticide in these circumstances and, in this respect, further recommendations of relevance are included in the parallel report on Termination of Pregnancy for Fetal Abnormality."

"Even as some research suggests that fetuses can feel pain as preterm babies do, other evidence indicates that they are anatomically, biochemically and psychologically distinct from babies in ways that make the experience of pain unlikely. The truth about fetal pain can seem as murky as an image on an ultrasound screen, a glimpse of a creature at once recognizably human and uncomfortably strange."

"IF THE NOTION that newborns are incapable of feeling pain was once widespread among doctors, a comparable assumption about fetuses was even more entrenched. Nicholas Fisk is a fetal-medicine specialist and director of the University of Queensland Center for Clinical Research in Australia. For years, he says, “I would be doing a procedure to a fetus, and the mother would ask me, ‘Does my baby feel pain?’ The traditional, knee-jerk reaction was, ‘No, of course not.’” But research in Fisk’s laboratory (then at Imperial College in London) was making him uneasy about that answer. It showed that fetuses as young as 18 weeks react to an invasive procedure with a spike in stress hormones and a shunting of blood flow toward the brain — a strategy, also seen in infants and adults, to protect a vital organ from threat. Then Fisk carried out a study that closely resembled Anand’s pioneering research, using fetuses rather than newborns as his subjects. He selected 45 fetuses that required a potentially painful blood transfusion, giving one-third of them an injection of the potent painkiller fentanyl. As with Anand’s experiments, the results were striking: in fetuses that received the analgesic, the production of stress hormones was halved, and the pattern of blood flow remained normal. Fisk says he believes that his findings provide suggestive evidence of fetal pain — perhaps the best evidence we’ll get. Pain, he notes, is a subjective phenomenon; in adults and older children, doctors measure it by asking patients to describe what they feel. (“On a scale of 0 to 10, how would you rate your current level of pain?”) To be certain that his fetal patients feel pain, Fisk says, “I would need one of them to come up to me at the age of 6 or 7 and say, ‘Excuse me, Doctor, that bloody hurt, what you did to me!’ ” In the absence of such first-person testimony, he concludes, it’s “better to err on the safe side” and assume that the fetus can feel pain starting around 20 to 24 weeks."

"Mark Rosen was the anesthesiologist at the very first open fetal operation, performed in 1981 at the University of California, San Francisco, Medical Center, and the fetal anesthesia protocols he pioneered are now followed by his peers all over the world. Indeed, Rosen may have done more to prevent fetal pain than anyone else alive — except that he doesn’t believe that fetal pain exists. Research has persuaded him that before a point relatively late in pregnancy, the fetus is unable to perceive pain. Rosen provides anesthesia for a number of other important reasons, he explains, including rendering the pregnant woman unconscious and preventing her uterus from contracting and setting off dangerous bleeding or early labor. Another purpose of anesthesia is to immobilize the fetus during surgery, and indeed, the drugs Rosen supplies to the pregnant woman do cross the placenta to reach the fetus. Relief of fetal pain, however, is not among his objectives. “I have every reason to want to believe that the fetus feels pain, that I’ve been treating pain all these years,” says Rosen, who is intense and a bit prickly. “But if you look at the evidence, it’s hard to conclude that that’s true.”"

"Whether the fetus feels pain is a question that matters to the doctor wielding the scalpel. And it matters, of course, for the practice of abortion. Over the past four years, anti-abortion groups have turned fetal pain into a new front in their battle to restrict or ban abortion. Anti-abortion politicians have drafted laws requiring doctors to tell patients seeking abortions that a fetus can feel pain and to offer the fetus anesthesia; such legislation has already passed in five states. Anand says he does not oppose abortion in all circumstances but says decisions should be made on a case-by-case basis. Nonetheless, much of the activists’ and lawmakers’ most powerful rhetoric on fetal pain is borrowed from Anand himself."

"Here we consider one final issue: whether nociceptive inputs may have deleterious consequences even if the “endogenously anesthetized” fetus does not consciously perceive pain at the time of stimulation. Can exposure to noxious stimuli initiate a cascade of events that sensitize the nervous system, or can repeated pain exposure in preterm infants contribute to attention, learning, and behavior problems later in life? It is critical to appreciate that not only is most of"

"We have considered whether the fetus, once its nociceptive pathways are complete, can feel pain in utero in a psychological manner akin to adult pain experience, and whether regardless of this the physiological responses to nociceptive input may lead to altered behavior later in life. We conclude that there is currently no strong evidence to suggest that the fetus is ever awake, even transiently; rather, it is actively kept asleep (and unconscious) by a variety of endogenous inhibitory factors."

"Twenty-five years ago, when Kanwaljeet Anand was a medical resident in a neonatal intensive care unit, his tiny patients, many of them preterm infants, were often wheeled out of the ward and into an operating room. He soon learned what to expect on their return. The babies came back in terrible shape: their skin was gray, their breathing shallow, their pulses weak. Anand spent hours stabilizing their vital signs, increasing their oxygen supply and administering insulin to balance their blood sugar. “What’s going on in there to make these babies so stressed?” Anand wondered. Breaking with hospital practice, he wrangled permission to follow his patients into the O.R. “That’s when I discovered that the babies were not getting anesthesia,” he recalled recently. Infants undergoing major surgery were receiving only a paralytic to keep them still. Anand’s encounter with this practice occurred at John Radcliffe Hospital in Oxford, England, but it was common almost everywhere. Doctors were convinced that newborns’ nervous systems were too immature to sense pain, and that the dangers of anesthesia exceeded any potential benefits. Anand resolved to find out if this was true. In a series of clinical trials, he demonstrated that operations performed under minimal or no anesthesia produced a “massive stress response” in newborn babies, releasing a flood of fight-or-flight hormones like adrenaline and cortisol. Potent anesthesia, he found, could significantly reduce this reaction. Babies who were put under during an operation had lower stress-hormone levels, more stable breathing and blood-sugar readings and fewer postoperative complications. Anesthesia even made them more likely to survive. Anand showed that when pain relief was provided during and after heart operations on newborns, the mortality rate dropped from around 25 percent to less than 10 percent. These were extraordinary results, and they helped change the way medicine is practiced. Today, adequate pain relief for even the youngest infants is the standard of care, and the treatment that so concerned Anand two decades ago would now be considered a violation of medical ethics. But Anand was not through with making observations. As NICU technology improved, the preterm infants he cared for grew younger and younger — with gestational ages of 24 weeks, 23, 22 — and he noticed that even the most premature babies grimaced when pricked by a needle. “So I said to myself, Could it be that this pain system is developed and functional before the baby is born?”"

"Rosen’s own hard look at the evidence came a few years ago, when he and a handful of other doctors at U.C.S.F. pulled together more than 2,000 articles from medical journals, weighing the accumulated evidence for and against fetal pain. They published the results in The Journal of the American Medical Association in 2005. “Pain perception probably does not function before the third trimester,” concluded Rosen, the review’s senior author. The capacity to feel pain, he proposed, emerges around 29 to 30 weeks gestational age, or about two and a half months before a full-term baby is born. Before that time, he asserted, the fetus’s higher pain pathways are not yet fully developed and functional. What about a fetus that draws back at the touch of a scalpel? Rosen says that, at least early on, this movement is a reflex, like a leg that jerks when tapped by a doctor’s rubber mallet."

"Our understanding of when the fetus can experience pain has been largely shaped by neuroanatomy. However, completion of the cortical nociceptive connections just after mid-gestation is only one part of the story. In addition to critically reviewing evidence for whether the fetus is ever awake or aware, and thus able to truly experience pain, we examine the role of endogenous neuro-inhibitors, such as adenosine and pregnanolone, produced within the feto-placental unit that contribute to fetal sleep states, and thus mediate suppression of fetal awareness. The uncritical view that the nature of presumed fetal pain perception can be assessed by reference to the prematurely born infant is challenged. Rigorously controlled studies of invasive procedures and analgesia in the fetus are required to clarify the impact of fetal nociception on postnatal pain sensitivity and neural development, and the potential benefits or harm of using analgesia in this unique setting."

"Whether the fetus can truly experience pain, at least in some way analogous to how adults emotionally understand pain, has been debated extensively over recent years and is of importance given continuing advances in fetal surgical and diagnostic procedures. This question has considerable implications for the management of invasive fetal procedures, particularly as fetal analgesic and anaesthetic treatment is complex and not without risk for the fetus. Prevention and treatment of pain are basic human rights, regardless of age, and if fetal interventions are to progress, then a greater understanding of nociception and stress responses is required. The timing of the neuroanatomical maturation of the nociceptive system is now well understood, and the final critical cortico-thalamic connections appear to be present by 24–28 weeks of gestation. This suggests that the fetus could potentially be able to feel pain by the third trimester, at least in a rudimentary fashion. This concept is said to be supported by studies which show that nociceptive stimuli elicit physiological stress-like responses in the human fetus in utero. However, physiological processing of a nociceptive stimulus and perceiving a nociceptive stimulus as painful are not the same. There are both a physiological and an emotional or cognitive aspect to pain perception, and indeed a significant element of learning [56]. Certainly, processing can be independent of perception, as is demonstrated during surgery under general anesthesia, for example, where nociceptive stimuli can still elicit subcortically mediated physiological stress responses despite unconsciousness. Thus, to emotionally experience pain, we must be cognitively aware of the stimulus (a cortical process), and this in turn requires that we must be conscious. The key question then is not about the anatomic completion or functionality of nociceptive pathways in utero, but whether the fetus is ever conscious and thus aware. In general, discussion of fetal pain perception tends to treat the fetus as an unborn newborn; i.e., that responses of the newborn represent an adequate surrogate for the fetus. The assumption is thus made that if the newborn (including the preterm newborn) can experience wakefulness (and therefore consciousness), and apparently feels pain, then so too must the age-equivalent fetus. Furthermore, evidence for fetal wakefulness (and again therefore consciousness) has been based on how certain fetal responses “resemble” newborn sleep–wake behaviors, rather than a true determination of fetal wakefulness per se. Given the complexities of studying the fetus, extrapolation from or to the newborn state is understandable. Systematic studies of fetal neurological function suggest, however, that there are major differences in the in utero environment and fetal neural state that make it likely that this assumption is substantially incorrect. This has important implications for our understanding of fetal pain perception. The current review critically evaluates the hypothesis that unlike the newborn, the fetus is actively maintained asleep (and unconscious) throughout gestation and cannot be woken by nociceptive stimuli. The evidence is examined with reference to fetal sleep–wake states, the role of cortico-thalamic gating in cortical arousal during sleep, and the unique contribution that certain inhibitory neuromodulators make in utero to cortical suppression. Finally, we briefly discuss the validity of the hypothesis that suggests that the nociceptive input may have long-lasting deleterious effects regardless of whether the fetus is asleep or not."

"Because pain perception probably does not function before the third trimester, discussions of fetal pain for abortions performed before the end of the second trimester should be noncompulsory. Fetal anesthesia or analgesia should not be recommended or routinely offered for abortion because current experimental techniques provide unknown fetal benefit and may increase risks for the woman. Instead, further research should focus on when pain-related thalamocortical pathways become functional in humans. If the fetus can feel pain, additional research may lead to effective fetal anesthesia or analgesia techniques that are also safe for women."

"Merker’s much-discussed article was accompanied by more than two dozen commentaries by prominent researchers. Many noted that if Merker is correct, it could alter our understanding of how normal brains work and could change our treatment of those who are now believed to be insensible to pain because of an absent or damaged cortex. For example, the decision to end the life of a patient in a persistent vegetative state might be carried out with a fast-acting drug, suggested Marshall Devor, a biologist at the Center for Research on Pain at Hebrew University in Jerusalem. Devor wrote that such a course would be more humane than the weeks of potentially painful starvation that follows the disconnection of a feeding tube (though as a form of active euthanasia it would be illegal in the United States and most other countries). The possibility of consciousness without a cortex may also influence our opinion of what a fetus can feel. Like the subplate zone, the brain stem is active in the fetus far earlier than the cerebral cortex is, and if it can support consciousness, it can support the experience of pain. While Mark Rosen is skeptical, Anand praises Merker’s work as a “missing link” that could complete the case for fetal pain."

"The processing of nociceptive stimuli requires peripheral sensory receptors, afferent and efferent sensory and motor pathways, and subcortical and cortical neural integration of the related impulse traffic. The development of nociceptive pathways has been extensively reviewed by others and is not the subject of this review. In brief, however, it is generally agreed that an integrated pathway exists by 24–28 weeks of gestation and that"

"The conclusion suggested in the section above is further strengthened by consideration of the increasing body of evidence which shows that there are several suppressors in utero which act to inhibit neural activity in the fetus to a far greater degree than is seen postnatally in the infant. The uterus plays a key role in providing the chemical and physical factors that together help to keep the fetus continuously asleep. We propose that this is achieved, among other things, through the combined"

"Likewise, the release of stress hormones doesn’t necessarily indicate the experience of pain; stress hormones are also elevated, for example, in the bodies of brain-dead patients during organ harvesting. In order for pain to be felt, he maintains, the pain signal must be able to travel from receptors located all over the body, to the spinal cord, up through the brain’s thalamus and finally into the cerebral cortex. The last leap to the cortex is crucial, because this wrinkly top layer of the brain is believed to be the organ of consciousness, the generator of awareness of ourselves and things not ourselves (like a surgeon’s knife). Before nerve fibers extending from the thalamus have penetrated the cortex — connections that are not made until the beginning of the third trimester — there can be no consciousness and therefore no experience of pain. Sunny Anand reacted strongly, even angrily, to the article’s conclusions. Rosen and his colleagues have “stuck their hands into a hornet’s nest,” Anand said at the time. “This is going to inflame a lot of scientists who are very, very concerned and are far more knowledgeable in this area than the authors appear to be. This is not the last word — definitely not.” Anand acknowledges that the cerebral cortex is not fully developed in the fetus until late in gestation. What is up and running, he points out, is a structure called the subplate zone, which some scientists believe may be capable of processing pain signals. A kind of holding station for developing nerve cells, which eventually melds into the mature brain, the subplate zone becomes operational at about 17 weeks. The fetus’s undeveloped state, in other words, may not preclude it from feeling pain. In fact, its immature physiology may well make it more sensitive to pain, not less: the body’s mechanisms for inhibiting pain and making it more bearable do not become active until after birth."

"Other investigators measured increases in fetal plasma concentrations of cortisol, β-endorphin, and noradrenaline associated with intrauterine needling procedures, finding that increases during blood sampling from the hepatic vein were greater than those during sampling from the umbilical cord. However, these neuroendocrine responses do not constitute evidence of fetal pain, because the autonomic nervous system and hypothalamic-pituitary-adrenal axis mediate them without conscious cortical processing. Additionally, these responses are not specific for painful stimuli. Plasma noradrenaline concentrations may increase after umbilical cord transfusion, and plasma β-endorphin concentrations may increase after repeated cordocenteses. Plasma cortisol and β-endorphin concentrations increase during innocuous activities such as exercise. Moreover, in adults, neuroendocrine stress responses may persist despite well-controlled postoperative pain. Vital signs also have been used to assess neonatal pain."

"Anesthetics and analgesics are commonly used to alleviate pain and discomfort. Despite ongoing debate regarding fetal capacity for pain, fetal anesthesia and analgesia are still warranted for surgical procedures undertaken to promote fetal health. When long-term fetal well-being is a central consideration, evidence of fetal pain is unnecessary to justify fetal anesthesia and analgesia because they serve other purposes unrelated to pain reduction, including (1) inhibiting fetal movement during a procedure; (2) achieving uterine atony to improve surgical access to the fetus and to prevent contractions and placental separation; (3) preventing hormonal stress responses associated with poor surgical outcomes in neonates; and (4) preventing possible adverse effects on long-term neurodevelopment and behavioral responses to pain. These objectives are not applicable to abortions. Instead, beneficence toward the fetus represents the chief justification for using fetal anesthesia or analgesia during abortion—to relieve suffering if fetal pain exists."

"Although widely used to assess pain in neonates, withdrawal reflexes and facial movements do not necessarily represent conscious perception of pain. Full-term neonates exhibit a “cutaneous withdrawal reflex” that is activated at a threshold much lower than that which would produce discomfort in a child or adult. This threshold increases with PCA, suggesting that the capacity of the neonate to distinguish between noxious and nonnoxious stimuli is maturing. Furthermore, flexion withdrawal from tactile stimuli is a noncortical spinal reflex exhibited by infants with anencephaly and by individuals in a persistent vegetative state who lack cortical function. Behavioral studies have also identified a distinct set of neonatal facial movements present during invasive procedures such as heel lancing but absent during noninvasive procedures. These facial movements, which are similar to those of adults experiencing pain, were evident in neonates at 28 to 30 weeks’ PCA but not at 25 to 27 weeks’ PCA. Facial movements may not necessarily be cortically controlled. One study found no difference in facial activity during heel lancing of neonates with and without significant cortical injury, suggesting that facial activity even around 32 weeks’ PCA may not represent conscious perception of pain."

"Hemodynamic and neuroendocrine changes in fetuses undergoing stressful procedures have also been used to infer pain perception. As early as 16 weeks’ gestational age, fetal cerebral blood flow increases during venipuncture and transfusions that access the fetal hepatic vein through the innervated fetal abdominal wall but not during venipuncture and transfusions involving the noninnervated umbilical cord. Increased cerebral blood flow is not necessarily indicative of pain, as this response is thought to constitute a “brain sparing” mechanism associated with hypoxia and intrauterine growth restriction."

"In contrast to fetal surgery requiring regional or general anesthesia, minimally invasive fetal procedures do not involve maternal laparotomy or hysterotomy and instead use needles or endoscopy to access the fetus. For the sake of reducing pain, the increased risks of general anesthesia are unjustified for these procedures; adults typically undergo similar procedures with no analgesia or only local analgesia."

"Despite this developmental role, no human study has shown that synapses between subplate and cortical plate neurons convey information about pain perception from the thalamus to the developing cortex."

"The histological presence of thalamocortical fibers is insufficient to establish capacity for pain perception. These anatomical structures must also be functional. Although no electroencephalographic “pain pattern” exists, electroencephalography may be one way of assessing general cortical function because electroencephalograms (EEGs) measure summated synaptic potentials from cortical neurons."

"Somatosensory evoked potentials (SEPs) may also provide evidence of pain processing in the somatosensory cortex, although they are not used clinically to test pain pathways. SEPs test the dorsal column tract of the spinal cord, which transmits visceral pain sensation to the somatosensory cortex via the thalamus. SEPs with distinct and constant N1 components of normal peak latency are present at 29 weeks’ PCA, indicating that thalamic connections with the somatosensory cortex are functional at that time."

"Pain is an emotional and psychological experience that requires conscious recognition of a noxious stimulus. Consequently, the capacity for conscious perception of pain can arise only after thalamocortical pathways begin to function, which may occur in the third trimester around 29 to 30 weeks’ gestational age, based on the limited data available. Small-scale histological studies of human fetuses have found that thalamocortical fibers begin to form between 23 and 30 weeks’ gestational age, but these studies did not specifically examine thalamocortical pathways active in pain perception. While the presence of thalamocortical fibers is necessary for pain perception, their mere presence is insufficient—this pathway must also be functional. It has been proposed that transient, functional thalamocortical circuits may form via subplate neurons around midgestation, but no human study has demonstrated this early functionality. Instead, constant SEPs appear at 29 weeks’ PCA, and EEG patterns denoting wakefulness appear around 30 weeks’ PCA. Both of these tests of cortical function suggest that conscious perception of pain does not begin before the third trimester. Cutaneous withdrawal reflexes and hormonal stress responses present earlier in development are not explicit or sufficient evidence of pain perception because they are not specific to noxious stimuli and are not cortically mediated."

"Another histological study of 12 specimens found that afferents from unspecified thalamic regions reached the developing prefrontal cortex in 1 preterm neonate of 27 weeks’ developmental age, concluding that thalamic fibers begin entering the cortex between 26 and 28 weeks’ developmental age (28 and 30 weeks’ gestational age). A different study found that thalamic afferents had not reached the somatosensory cortical plate by 22 weeks’ developmental age (24 weeks’ gestational age). By 24 weeks’ developmental age (26 weeks’ gestational age), the density of cortical plate synapses increased, although these were not necessarily from thalamic afferents. Based on these studies, direct thalamocortical fibers that are not specific for pain begin to emerge between 21 and 28 weeks’ developmental age (23 and 30 weeks’ gestational age)."

"In the context of abortion, fetal analgesia would be used solely for beneficence toward the fetus, assuming fetal pain exists. This interest must be considered in concert with maternal safety and fetal effectiveness of any proposed anesthetic or analgesic technique. For instance, general anesthesia increases abortion morbidity and mortality for women and substantially increases the cost of abortion. Although placental transfer of many opioids and sedative-hypnotics has been determined, the maternal dose required for fetal analgesia is unknown, as is the safety for women at such doses. Furthermore, no established protocols exist for administering anesthesia or analgesia directly to the fetus for minimally invasive fetal procedures or abortions. Experimental techniques, such as administration of fentanyl directly to the fetus and intra-amniotic injection of sufentanil in pregnant ewes, have not been shown to decrease fetal pain and are of unknown safety in humans."

"“Before a symbolic system such as language, an individual will not know that something in front of them is large or small, hot or cold, red or green” — or, Derbyshire argues, painful or pleasant. He finds “outrageous” the suggestion that the fetus feels anything like the pain that an older child or an adult experiences. “A fetus is biologically human, of course,” he says. “It isn’t a cow. But it’s not yet psychologically human.” That is a status not bestowed at conception but earned with each connection made and word spoken. Following this logic to its conclusion, Derbyshire has declared that babies cannot feel pain until they are 1 year old. His claim has become notorious in pain-research circles, and even Derbyshire says he thinks he may have overstepped. “I sometimes regret that I pushed it out quite that far,” he concedes. “But really, who knows when the light finally switches on?”"

"Even birth may not inaugurate the ability to feel pain, according to Stuart Derbyshire, a psychologist at the University of Birmingham in Britain. Derbyshire is a prolific commentator on the subject and an energetic provocateur. In milder moods, he has described the notion of fetal pain as a “fallacy”; when goaded by his critics’ “lazy” thinking, he has pronounced it a “moral blunder” and “a shoddy, sentimental argument.” For all his vehemence in print, Derbyshire is affable in conversation, explaining that his laboratory research on the neurological basis of pain in adults led him to the matter of what fetuses feel: “For me, it’s an interesting test case of what we know about pain. It’s a great application of theory, basically.” The theory, in this case, is that the experience of pain has to be learned — and the fetus, lacking language or interactions with caregivers, has no chance of learning it. In place of distinct emotions, it experiences a blur of sensations, a condition Derbyshire has likened to looking at “a vast TV screen with all of the world’s information upon it from a distance of one inch; a great buzzing mass of meaningless information,” he writes."

"Nothing begins, and nothing ends, That is not paid with moan; For we are born in others' pain, And perish in our own."