"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."
— Pain

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