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Fetal Pain a Systematic Multidisciplinary Review of the Evidence

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Fetal Pain a Systematic Multidisciplinary Review of the Evidence CLINICAL REVIEW CLINICIAN’S CORNER Fetal Pain A Systematic Multidisciplinary Review of the Evidence Susan J. Lee, JD Context Proposed federal legislation would require physicians to inform women Henry J. Peter Ralston, MD seeking abortions at 20 or more weeks after fertilization that the fetus feels pain Eleanor A. Drey, MD, EdM and to offer anesthesia administered directly to the fetus. This article examines whether a fetus feels pain and if so, whether safe and effective techniques exist for John Colin Partridge, MD, MPH providing direct fetal anesthesia or analgesia in the context of therapeutic proce- Mark A. Rosen, MD dures or abortion. Evidence Acquisition Systematic search of PubMed for English-language articles VER THE LAST SEVERAL focusing on human studies related to fetal pain, anesthesia, and analgesia. Included years, many states, includ- articles studied fetuses of less than 30 weeks’ gestational age or specifically addressed ing California, Kentucky, fetal pain perception or nociception. Articles were reviewed for additional references. Minnesota, Montana, New The search was performed without date limitations and was current as of June 6, OYork, Oregon, and Virginia, have con- 2005. sidered legislation requiring physi- Evidence Synthesis Pain perception requires conscious recognition or awareness cians to inform women seeking abor- of a noxious stimulus. Neither withdrawal reflexes nor hormonal stress responses to tions that the fetus feels pain and to offer invasive procedures prove the existence of fetal pain, because they can be elicited by fetal anesthesia. This year, Arkansas and nonpainful stimuli and occur without conscious cortical processing. Fetal awareness Georgia enacted such statutes.1,2 Cur- of noxious stimuli requires functional thalamocortical connections. Thalamocortical fi- rently, Congress is considering legisla- bers begin appearing between 23 to 30 weeks’ gestational age, while electroencepha- tion requiring physicians to inform lography suggests the capacity for functional pain perception in preterm neonates prob- ably does not exist before 29 or 30 weeks. For fetal surgery, women may receive general women seeking abortions 20 or more anesthesia and/or analgesics intended for placental transfer, and parenteral opioids weeks after fertilization (ie, 22 weeks’ may be administered to the fetus under direct or sonographic visualization. In these gestational age) that the fetus has “physi- circumstances, administration of anesthesia and analgesia serves purposes unrelated cal structures necessary to experience to reduction of fetal pain, including inhibition of fetal movement, prevention of fetal pain,” as evidenced by “draw[ing] away hormonal stress responses, and induction of uterine atony. from surgical instruments.” The physi- Conclusions Evidence regarding the capacity for fetal pain is limited but indicates cian must also offer anesthesia or anal- that fetal perception of pain is unlikely before the third trimester. Little or no evidence gesia “administered directly” to the fe- addresses the effectiveness of direct fetal anesthetic or analgesic techniques. Simi- tus. Physicians who do not comply may larly, limited or no data exist on the safety of such techniques for pregnant women in be subject to substantial fines, license re- the context of abortion. Anesthetic techniques currently used during fetal surgery are vocation, and civil suits for punitive not directly applicable to abortion procedures. damages.3 JAMA. 2005;294:947-954 www.jama.com Although this legislation would not affect most US abortions because only step in answering these questions, we Author Affiliations: School of Medicine (Ms Lee), 1.4% are performed at or after 21 weeks’ reviewed the literature on fetal pain and Department of Anatomy and W. M. Keck Founda- gestational age,4 this legislation raises tion for Integrative Neuroscience (Dr Ralston), and fetal anesthesia and analgesia. Departments of Obstetrics, Gynecology and Repro- important scientific, clinical, ethical, ductive Sciences (Drs Drey and Rosen), Pediatrics and policy issues. When does a fetus EVIDENCE ACQUISITION (Dr Partridge), and Anesthesia and Perioperative have the functional capacity to feel Care (Dr Rosen), University of California, San Fran- English-language articles involving hu- cisco. pain? If that capacity exists, what forms man participants were searched using Corresponding Author: Mark A. Rosen, MD, Depart- of anesthesia or analgesia are safe and ment of Anesthesia and Perioperative Care, Univer- PubMed for (1) fetal pain (16 articles), sity of California, San Francisco, 513 Parnassus Ave, effective for treating fetal pain? As a first San Francisco, CA 94143-0648 (rosenm@anesthesia fetal anesthesia (6 articles), and fetal an- .ucsf.edu). algesia (3 articles); (2) fetus and (anes- Clinical Review Section Editor: Michael S. Lauer, MD. CME available online at thesia or analgesia) (1239 articles); (3) We encourage authors to submit papers for consider- www.jama.com ation as a “Clinical Review.” Please contact Michael S. Medical Subject Headings (MeSH) an- Lauer, MD, at [email protected]. ©2005 American Medical Association. All rights reserved. (Reprinted) JAMA, August 24/31, 2005—Vol 294, No. 8 947 Downloaded From: https://jamanetwork.com/ on 09/25/2021 FETAL PAIN algesics/administration and dosage and fe- Figure. Spinal Reflex and Pain Perception Pathways tus (44 articles); (4) MeSH anesthesia/ administration and dosage and fetus (0 A Spinal Reflex articles); (5) (neurodevelopment or devel- opment or anatomy) and (fetus or fetal) Dorsal Root Ganglion SPINAL CORD and (pain or nociception or noxious)(306 articles); (6) (thalamocortical or thala- 2 Peripheral 3 Dorsal Horn mus or cortex) and (fetus or fetal) and Sensory Neuron Interneuron (pain or nociception or noxious) (13 ar- ticles); (7) (electroencephalog* or EEG or 1 Noxious evoked potential) and (fetus or fetal or pre- Stimulus mature neonate or premature infant or pre- 4 Ventral Horn term neonate or preterm infant) and (pain Motor Neuron or nociception or noxious or conscious*) C LE M US (7 articles); (8) fetal and pain and (re- 5 Contraction sponse or assessment or facial expres- sion) (112 articles); and (9) facial expres- sion and (fetus or fetal)or([neonate or neonatal or infant] and [premature or pre- B Pain Perception via the Spinothalamic Tract term]) and (pain or nociception or nox- ious) (360 articles). The search was per- C BRAIN OR formed without date limitations and was T EX current as of June 6, 2005. From these 6 Thalamocortical Axon 7 Perception search results, we excluded articles that did not study fetuses of less than 30 weeks’ gestational age or that did not spe- 5 Thalamus cifically address fetal pain perception or nociception. With a focus on topics ad- dressed by earlier review articles on fe- tal pain, anesthesia, and analgesia, ar- ticles were reviewed for additional references. EVIDENCE SYNTHESIS 4 Spinothalamic What Is Pain? 3 Spinothalamic Tract Pain is a subjective sensory and emo- Neuron tional experience that requires the pres- Dorsal Root Ganglion ence of consciousness to permit recog- nition of a stimulus as unpleasant.5-7 2 Peripheral Sensory Neuron Although pain is commonly associated with physical noxious stimuli, such as when one suffers a wound, pain is fun- damentally a psychological construct that 1 Noxious may exist even in the absence of physi- Stimulus cal stimuli, as seen in phantom limb SPINAL CORD pain.5,7 The psychological nature of pain also distinguishes it from nociception, which involves physical activation of no- ciceptive pathways without the subjec- A, Reflex responses to noxious stimuli occur early in development, before thalamocortical circuits are func- 5,8 tional; noxious stimuli trigger reflex movement without cortical involvement. Activated by a noxious stimulus tive emotional experience of pain. For (1), a peripheral sensory neuron (2) synapses on a dorsal horn interneuron (3) that in turn synapses on a ven- example, nociception without pain ex- tral horn motor neuron (4), leading to reflex muscle contraction and limb withdrawal (5). B, Later in develop- ists below the level of a spinal cord le- ment, noxious stimuli (1) activate peripheral sensory neurons (2) that synapse on spinothalamic tract neurons (3), the axons of which extend up the spinal cord as the spinothalamic tract (4) to synapse on neurons of the sion, where reflex withdrawal from a thalamus (5). From here, thalamocortical axons synapse on cortical neurons, resulting in the conscious per- noxious stimulus occurs without con- ception of pain. scious perception of pain (FIGURE, A).5 948 JAMA, August 24/31, 2005—Vol 294, No. 8 (Reprinted) ©2005 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 FETAL PAIN Table. Anatomical and Functional Development of Nociception and Pain Perception Pathways Anatomical/ Gestational Functional Characteristic Description Age, wk Source Peripheral cutaneous sensory receptors Perioral cutaneous sensory receptors 7.5 Palmar cutaneous sensory receptors 10-10.5 Humphrey,13 1964 Abdominal cutaneous sensory receptors 15 Spinal cord Spinal reflex arc in response to nonnoxious stimuli 8 Okado and Kojima,14 1984 Neurons for nociception in dorsal root ganglion 19 Konstantinidou et al,15 1995 Thalamic afferents Thalamic afferents reach subplate zone 20-22 Kostovic and Rakic,16 1990 Hevner,17 2000 Thalamic afferents reach cortical plate 23-24 Kostovic and Rakic,18 1984 Kostovic and Goldman-Rakic,19
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