Zielinski on fetal pain


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Zielinski on fetal pain

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Zielinski on fetal pain

  1. 1. My focus today is on the basics of fetal pain, the elements of thescience and the implications of ongoing research. While I willtouch on religious and social justice aspects of the issue, myperspective is almost brutally scientific. To understand that, youneed to know a little bit about where I came from.Though pro-abortion in High school, I remember well the collegehuman embryology class when I was looking at slides of fetaldevelopment. While I kept saying to myself 36 weeks, 38 weeks,40 weeks gestation, my professors were saying 6 weeks, 8weeks, 10 weeks. It was that difference, between what I saw withmy own eyes, rather than the propaganda I had been fed, that leftme convicted to the pro-life cause aand led me to become one ofthe first researchers on Fetal Pain.To understand the status of fetal pain science today, you have tounderstand where we were, circa 1978. A concerted effort wasmade to convince the public that there was no such thing as anunborn child. The miracle of birth was, apparently, just that...somehow, on the way down the birth canal, a mere collection ofcells congealed into a baby. Like Jello 1-2-3. I mean, if we coulddrink Carnation Instant Breakfast, why couldnt we have CarnationInstant Baby?The general belief was that newborns didnt feel and experiencepain, at least not in the sense that you and I did. Circumcisionswere done without analgesia - and any concerns regardingdiscomfort were dismissed as having no lasting effect. Newbornsurgery was done with a definitive form of anesthesia - adhesivetape. The newborn was simply taped to the operating table andsurgery went on without regard for struggles or screams.Newborn surgery had a high mortality, but, since the newbornliver was unable to tolerate drugs, surgery was considered saferwithout ANY anesthesia. The idea of an unfeeling newborn was
  2. 2. so fixed in mainstream medical thought that any contrary proposalwas openly mocked and ridiculed.My research colleagues, Dr. Vincent Collins and Mr. ThomasMarzen, asked a simple question, If the unborn child looks humanand moves like a human, at what point can the unborn childrespond to pain like a human? Communicating that pain might bedifficult, but that had not blocked efforts to limit suspected pain forexperimentation on monkeys, dogs and even lab rats. Yet I canvividly recall being on an elevator with 2 of my peers, leadingobstetrician-gynecologists at my medical school, who, well awareof my research, openly laughed while claiming, "Oh, well have togive aspirins for circumcisions! Oh, well have to find ananesthetist before we operate!"Today, of course, to do a circumcision without analgesics wouldbe considered barbaric. To do newborn - and even intrauterinesurgery without anesthesia would be gross malpractice.Opioid analgesics are routinely used to supplement generalanesthesia for fetal surgery to minimize procedural pain. Localanesthetics are used to prevent pain from minor procedures inpre-term neonates, especially in the Intensive Care Unit. (Sal)The benefits of using anesthesia for neonatal and intrauterinesurgery have been nothing short of astounding, reducing mortalityby more than one-third.The science of fetal pain is simple, as all science must be.Pain can be defined as an unpleasant sensory and emotionalexperience associated with actual or potential tissue damage, ordescribed in terms of such damage. Both science and experienceshow us that the fetus and the preterm neonate are capable offeeling the unpleasant sensory experience of actual tissuedamage. (Grissom)
  3. 3. Dr. Collins, Mr. Marzen and I followed a rational method that hadbeen used as a basis for the existence of pain in all manner ofanimals and in non-communicative individuals of every age. Suchobjective evidence is regularly used even when patients andanimals are UNDER anesthesia to determine the adequacy oftreatment. Method was outlined in a 1983 paper by Kitchell andErickson titled Animal Pain: Perception and Alleviation.The three components of this method are structure, function,and the demonstration of an aversive response to a noxiousstimulus.StructureFor structure, you must show the presence of pain receptors,called nociceptors, in the skin. Next, Nerves to carry nociceptorsignals to the spinal cord and upward in the central nervoussystem and, finally, a brain structure to receive, process andrespond to the signals.The scientific literature has documented the presence of fully-functioning sensory receptors in the skin around the mouth of thefetus at 6 weeks gestational age. (salvacion)Nociceptors are readily identifiable in the skin by the 7th week ofgestation and under a microscope look like small bushes or thefrayed end of a rope. They appear everywhere in the tissues ofthe skin, muscle, bones, and organs. These cells respond todifferent forms of energy such as pressure, heat, or cold - andconvert this information into electrical activity. (Salvacion)Specialized nerve endings involved in pain transmission are foundthroughout all organs by 20 weeks gestation. These nerves
  4. 4. connect to other nerves in the dorsal horn of the spinal cord.(Think Dorsal Fin of a Shark).No less an authority than Leslie B. Arie, the father of HumanEmbryology, documented the existence of these spinal nerves,already appearing as spinal cord structures - specializedpathways called TRACTS, on embryos in the first six weeks oflife.At the top of the spinal cord, these nerves enter a group of berryand nut-sized clusters of brain cells collectively known as thebasal ganglia. One of the more central of these clusters is calledthe thalamus.The thalamus acts as a central processing center for sensoryinformation from the rest of the body. The thalamus is THEcritical brain structure necessary for pain sensation and response.The thalamus is present at least as early as the 5th week ofdevelopment. As I will explain, these are all the structuresnecessary for pain sensation and response. While the cerebralcortex starts to form at about 8-10 weeks gestational age, thecortex is not, and has never been, a critical pain perceptionstructure.FunctionBut structure alone is not enough. Functional activity in thesestructures must also be present. A wide variety of demonstrableevents can illustrate that tissue function among pain structures ispresent. You may take your pick.Electrical activity
  5. 5. At only 40 days after fertilization electrical waves as measured bythe EEG can be recorded from the babys brain, indicating brainfunctioning. This coincides with electrical activity up and downthe spinal cord.Identifiable EEG activity is seen from 19-20 weeks gestationalage and sustained EEGs can be recorded from fetuses of 23weeks gestational age. (Sal)Chemical pain substances, neurotransmittersThe neurotransmitters in the spinal cord that mediate paintransmission appear early in development and are abundant.(Salvacion) They include Substance P, L-glutamate, CGRP,(Wright - cong test.) calcitonin gene-related peptide, VIP,vasoactive intestinal polypeptide, somatostatin and bombesin.In an article on Neurotransmitters and neuromodulators during early humandevelopment :Neurotransmitters such as monoamines appear in the embryo atless than 8 weeks, before the nerves are differentiated. Maybe some of them remainas evolutionary residues. NMDA (Glutamate) receptors dominate in the foetus, while kainateand AMPA receptors appear later. Neurotransmitters and modulators are not only important forthe neural trafficking in the embryo, but also for the development of the neuronal circuits.(Actually creating the wiring). Prenatal or neonatal stress may disturb the wiring and cause long-term behavioural effects.” (Best known example is abnormal pain processing followingcircumcision without analgesia) This, notably, is evidence of fetal and neonatalprogramming.GlutamateThe NMDA (Glutamate) receptor mediates a host of spinal responses to severe painfulstimulation. Consequences of glutamate receptor activation include production of c-fos andspinal production of prostanoids and nitric oxide.
  6. 6. G-ABAGABA is widespread in the brain and spinal cord. Together with its partner glycine, it has majorinhibitory effects.Hormonal responsesA study of intrauterine blood sampling and blood transfusions in fetusesbetween 20 and 34 weeks of gestation showed that hormonal responsesto the needle sticks were consistent with the fetal perception of pain andwere correlated with the duration of the painful stimulus. (Wright)These hormones are present in umbilical cord blood in response to stressin the 16th week and possibly sooner.The final component necessary for establishing the presence of fetalpain is an Aversive response to a noxious stimulus.Full body aversive responses to painful stimuli can be easilywitnessed on ultrasound at 13-1/2 weeks gestation. That was theobvious conclusion reached by Dr. Collins, Mr. Marzen and Iwhen we published "Abortion and fetal Pain: The MedicalEvidence" in 1984. Our greatest limitation for any conclusionsprior to that time in fetal development was the limited clarity ofexisting ultrasound. But we had research reports fromexperiments done on fetuses aborted in the first trimester thatsupported our findings.Other evidence of aversive responses:From 16 weeks gestation, the typical change in brain circulation is seenin the fetal brain in response to a painful stimulus. Wladimiroff JW et. al. Obstet Gynecol 1987;69:705-9 (Ran)Further physiologic response to painful stimuli include increased levels ofcirculating hormones like cortisol and catecholamines (epinephrine) in
  7. 7. response to painful stimuli. These levels will actually increase inrelationship to the level of painful stimulation.Pain and surgical stress are also demonstrated by a coordinatedoutpouring of hormones from the pancreas, pituitary and adrenalglands. Cardiovascular responses such as increases in bloodpressure and heart rate, abnormal heart rhythms, or poor cardiacoutput may signal pain.As we noted, Fetuses have been observed to exhibit hormonalstress responses to painful stimuli as early as 16 weeksgestational age. Studies have demonstrated the significantincrease in stress hormones following needle placement in thefetal abdomen for in utero blood transfusions. In contrast, noconsistent hormonal response occurred in the fetuses transfusedthrough the umbilical cord, a structure which does not containpain receptors. These responses were reduced when painmedication was administered directly to the fetus, demonstratingthat pain processing and the ability to ameliorate painpharmacologically is present in the fetus. So much for thatfamous pro-choice song – It’s my body and I’ll kill if I want to.(Sal)Studies of electrical activity including EEGs and SEPs show that the fetus responds topainful stimuli in the same way that infants do by 24 weeks gestation. In fact theresponses are exaggerated because the inhibitory pathways involved in moderatingpain signal transmission do not develop in the fetus until 34-36 weeks gestation.(Grissom)The administration of anesthesia to preterm infants with surgicalprocedures not only reduced abnormal EEG patterns, it was alsocorrelated with better outcomes (grissom)Various ExcusesCant speak, cant feel pain.
  8. 8. Tell someone you are going to torture a lab rat or stick a knife in adog. Is there anyone who honestly believes that if they dont say"Ouch" they cant feel pain? People have gone to jail for less. Sowhen PETA comes to your door looking for a donation, be sure toask them to contribute to your local crisis pregnancy center. Afterall, humans are animals, too.The inability to communicate verbally does not negate thepossibility that an individual is experiencing pain. Pain can beexpressed non verbally by movement in responses to a stimulusor physiological changes, such as changes in heart rate or bloodpressure. (Salvaccion)Adults who are unconscious and brain damaged can beassessed for pain responses. Decorticate and decerebraterigidity are 2 full body responses often seen with painful stimuli.Blood pressure, pulse, EEG and hormonal responses - along withcirculatory changes - are all used as stand-ins for pain whencommunication is not available.ReflexYou will be told "pay no attention to those movements, its only areflex." If you place an object in the fetal palm at 8 weeks, thehand may close around it. That is a reflex. If you poke the handwith a sharp needle, the hand and arm may withdraw. That maybe a reflex. If, however, the neck arches and the mouth opensand you see other components of a full body aversive response,that is no longer a reflex. Modern ultrasound shows this
  9. 9. definitively at 13 weeks and it is only limited by a lack of clarity at8 weeks. Not a reflex. The tail does not wag the dog.We could not see such full body aversive responses on theprimitive ultrasounds of the early 1980s. Modern 3-D and 4-Dultrasound is so good, you can even see the face grimace in pain.Try it sometime; show an intrauterine ultrasound to a pro-choicezealot. The painful facial grimaces they make are just amazing.No myelin - no pain.Myelin is made up of a cell, separate from the actual nerve cell,which coats and surrounds the length of the nerve cell. Myelin isnot necessary for a nerve cell to work, its presence only meansthat the nerve cell signal is able to travel faster. This can beimportant when you are six feet tall. It becomes a little lessimportant when you are only one inch tall. Myelin has beenshown to only be relevant to how quickly you respond to pain, ithas nothing to do with whether or not pain is perceived.(Talk about MS - lack of myelin. May be numbed, may be slow.)No CortexAll the brain segments have obviously started to form by 5 weeks.The midbrain, brainstem and cortex are all present in the fetus by20 weeks gestation. This means that all the elements for theperception of pain are present by 20 weeks gestation. (Grissom)But no cortex is needed to experience and respond to pain. Thecritical structure is the thalamus.How do we know? People who have suffered the removal oflarge portions of their cerebral hemispheres can still feel andrespond to pain. If I cut off the top of your head, I could stick pins
  10. 10. into your cortex all day and you would not feel pain. I could usecaustic chemicals or electric shocks and you would report nothingmore than an odd buzzing sensation. If I did any of these thingsto the thalamus, extreme pain responses would occur. We alsoknow, in medicine, about Thalamic Pain Syndrome where thebody becomes hypersensitive to pain as a result of damage to thethalamus. In TPS, Pain or discomfort may be felt after beingmildly touched or even in the absence of a stimulus. The paincan be excruciating and often requires centrally acting narcotics,anti-depressants and seizure medications to control.Connections between the thalamus and cortex begin to appear asearly as 20 weeks gestational age. (Salvacion) and the cortex isvery important for localizing exactly WHERE pain is, but aninsistence on a functioning cortex is absurd. Its a lot like saying atornado didnt do any damage because we cant show you on amap where it hit. The pain, like the tornado, still hurts.Minimal or incomplete responseWhile some nay sayers go to great lengths to argue that all theextensive nuances of adult pain sensation and response may notbe present, this does nothing to minimize the presence of fetalpain. Newborns not only feel pain; they react to pain with 3 – 5times the response of adults. They require higher doses ofanesthesia during surgery, and repeated exposure to pain lowersthe threshold to pain even more. (Wright) Newborns, like fetuses,lack the development of inhibitory systems for pain reduction, sothat the painful consequences of relatively minor stimulation areexaggerated.Another argument, No memoryThe argument is, if you havent experienced pain, you dont knowwhat it is. But research now shows that INTRA-UTERINE painfulstresses may produce changes in memory patterns for pain
  11. 11. PRIOR to birth. Additional studies are beginning to elucidate theactual GENETIC code of pain sensation and response. In an article titled “Stressed-out, or in (utero)?”AbstractThe molecular and cellular mechanisms by which plasticity is induced in the mature CNS (and, specifically, in the hippocampus) byenvironmental input are progressively being elucidated. However, the mechanisms – and even the existence – of functional and structural effectsof environmental input (and, particularly, stress) early in life are incompletely understood. Here, we discuss recent evidence thatstressful stimuli have a significant impact on neonatal (rat) andprenatal (human) hippocampal function and integrity.Stressful signals provoke expression and release of neuromodulators, including the peptide corticotropin-releasing hormone (CRH), leading toactivation of CRH receptors on principal hippocampal neurons. Although physiological activation of these receptors promotes synaptic efficacy, early-life stress couldpathological levels of CRH at hippocampal synapses contribute to neuronal death. Thus,constitute a ‘double-edged sword’: mild stress mightpromote hippocampal-dependent cognitive function,whereas severe stress might impair neuronal function andsurvival, both immediately and in the long-term. Importantly, theseCRH-mediated processes could be targets of preventive and interventional strategies.Finally for those who believe Fetal Pain is more religious dogmathan actual science, I offer this:If you believe in evolution - and all that implies for theembryological development of the human species - you cannothelp but endorse the concept that pain sensation and response,including fetal pain, would develop in evolutionary time at theearliest possible moment as an essential mechanism of survival.For those who seek to shove evolution down the throats of Bible-Believing Christians, now is not the time to abandon yourscientific principles. Welcome, Mr. Darwin, to the Pro-lifemovement!Something needs to be said about my colleagues, because theycannot be here today. We published in 1984, in an effort to aidPresident Ronald Reagan, who had come under fire for hiscomments on fetal pain. He based his original comments on our
  12. 12. research, which was taken from my desk drawer and provided tothe White House by a republican political operative. Based on theoutcry over Reagans comments, you would have thought thePresident had denied the Holocaust, when in fact he was drawingattention to it.We published three years before Dr. Anand, who is often -anderroneously, given credit for the concept of fetal pain. VincentCollins, our lead author, was a Professor of Anesthesiology atNorthwestern University and the University of Illinois. He was thefirst chairman of Anesthesiology at Cook County Hospital inChicago. He authored numerous research articles onAnesthesiology, including a major textbook in the field. He died in2004, at the age of 90. If you Google him, he is remembered for2 things - Cook County Hospital - and fetal pain.Thomas Marzen was a noted pro-life attorney who was activelyinvolved in all aspects of the movement. He was, withoutquestion, the architect of the rigorous research protocol we usedto prove the existence of fetal pain. Tom, who was probably oneof the brightest and most compassionate men I have ever met,suffered from polycystic kidney disease. He endured kidneyfailure and a kidney transplant. He died in 2007 fromcomplications of cancer. Both he and Dr. Collins had the joy ofknowing they made a difference.The recognition of fetal pain led to a re-assessment of treatmentfor the unborn and the neonate. The introduction of anesthesiaand analgesia, along with an enhanced recognition of thehumanity and uniqueness of each human life, has savedthousands of lives. Absent the entire issue of abortion, countlessnumbers of newborns were saved because they had access toanesthesia as part of their lifesaving surgery. Absent the pro-lifemovement, the questions might never have been asked, theanswers never sought.
  13. 13. And so, on behalf of my colleagues - and on behalf of the pro-lifemovement that stood with us, when the rest of the world laughedat us and mocked us - I claim those lives! Know that these liveswere saved. Know that, despite the pain, you did good.While unborn children in the womb may be pro-choice, theyalmost universally choose life.Some postscripts…http://www.anaesthetist.com/icu/pain/Findex.htm#pain3.htmProbably the most significant discovery ever in the field ofpain has been the gene c-fos. The cellular analogue of a viraloncogene, this rather special gene and its cellular product, theprotein called Fos seem crucial to the profound central nervoussystem changes that occur when an animal (or man) feels pain.Central nervous system c-fos expression correlates extremelywell with painful stimulation. Generically, Fos is one of theinducible transcription factors (ITFs) that controls mammaliangene expression.We now have a molecular marker for pain! Even moreimportant, we know that because c-fos is a proto-oncogene - thatis, it can promote vast intracellular changes including cellularrestructuring and proliferation - it is almost certainly involved inthe long-term neurological consequences of noxious stimulation.An incidental note - FOS has been found in the fetal bones atleast as early as the 16th week of gestation.CONCLUSIONIt doesnt matter if you start with the FOS gene in the fertilizedegg at the moment of conception or work backward from wherewe left off with the 8 week embryo and the lab animals who cantcommunicate their agony.
  14. 14. The Future: Knowing the earliest moments when humans can feeland respond to pain, you will understand the mechanisms at abasic level; you will be able to develop new drugs and newmethods to relieve pain, prevent disease and modify the course ofillness.Our opponents will not challenge us on fetal pain because theyknow that their scientists are with us and they fear the direconsequences if they ever prove us wrong. Kittens would betortured in the streets, you couldn’t fundraise off the slaughter ofhelpless baby seals, Michael Vick would not only be exoneratedin the SuperBowl, his pets would be the halftime show.