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Pain and the fetus
1.  What is fetal sentience?
2.  Why the recent interest in fetal sentience?
3.  When does fetal sentience become anatomically possible?

1.  何谓胎儿感觉？
2.  为什么最近的很多研究集中于胎儿感觉？
3.  胎儿感觉什么时候在解剖上成为可能？

参考答案：

1.何谓胎儿感觉？

胎儿感觉是指胎儿感受疼痛或不愉快感觉的能力[1]。对该现象的讨论涉及到语义学上的问题。如果疼痛是一种“与实际或潜在的组织损伤相关的不愉快感觉和情绪体验”，那么胎儿所经历的感觉和（/或）以后对该感觉的理解是怎样的？然而，国际疼痛研究协会[2]推荐的疼痛定义包括对不愉快体验的确认和口头表达，这个如何应用于胎儿？这种“痛苦和不适”如何检测？这些限制促使Anand和Hickey提出，在讨论胎儿“疼痛”时应取消伤害性疼痛的称法[3]。

2.为什么最近的很多研究集中于胎儿感觉？

最近，先天畸形宫内外科矫治手术和胎儿组织在器官移植中的使用得到发展，这促使人们开始关注胎儿感觉。

3.胎儿感觉什么时候在解剖上成为可能？

关于胎儿感觉的几个推断建立在四、五十年前进行的宫外胎儿实验的基础上，但这些实验并未明确测试“疼痛”刺激的反应性[1]。最近，对胎儿神经系统功能进行了直接观察，但是这些研究受到对照间系统功能发育成熟与否不确定的限制[1]。

Flower[4]研究认为胎儿感觉只有到妊娠中期才有可能出现。虽然在发育8周中枢神经系统即可有活性，在妊娠前三月结束时脑干具有活性（可充当感觉信息和运动功能的未完全发育的调制器），但是Flower表示，新皮质不会成为神经轴有功能的一部分，直到至少妊娠中期，丘脑（感觉传入大脑的主要通路）发挥其首先与新皮质系统输入联系的功能。Flower认为，如果不存在功能性丘脑的连接，就不存在感觉。

在妊娠26周丘脑-皮层连接形成后，疼痛的皮质突通路在理论上成为可能，伤害性刺激可触发复杂反射性反应。利用抗体检测已知与疼痛刺激神经传递有关的小多肽，很多研究者提出了一个胎儿感觉的更早期的时间范围，在妊娠10-12周时发现有P物质、脑啡肽和神经微丝蛋白[5]。虽然这些发现的相关性尚不明确，但是Vanhatalo等[6]认为，通过触发应激反应，在非常早的阶段，个体的行为发育可受到不良影响。因此，虽然据此推测胎儿或早产儿对疼痛可能产生情绪体验并不合理，但是需要更进一步的研究以评估胎儿感觉的长期可能结果。

What is fetal sentience?

Fetal sentience is the capacity of the fetus to experience painful or unpleasant sensation (1). Complicating the discussion of this phenomenon are the semantics involved. If pain is an "unpleasant sensory and emotional experience associated with actual or potential tissue damage", what emotional and/or future apprehension is experienced by a fetus? Moreover, as the definition of pain as proposed by the International Association for the Study of Pain (2) assumes recognition and verbal expression of an unpleasant experience, how does this apply to the fetus? How is "suffering and distress" detected? These limitations have led Anand and Hickey to suggest that "nociceptive activity" should be substituted in the discussion of fetal "pain" (3).

Why the recent interest in fetal sentience?

The recent expansion of in-utero surgical correction of congenital anomalies and the use of fetal tissues for transplantation have spurred the debate on fetal sentience.

When does fetal sentience become anatomically possible?

Several inferences have been made regarding fetal sentience based on ex-utero fetal experimentation 4-5 decades ago; however, these studies did not test explicitly for response to "painful" stimuli (1). More recently, direct observations regarding the function of fetal nervous systems have been made, but these studies are limited by uncertainty regarding comparisons between mature and immature systems (1).

This being said, Flower (4) argues that fetal sentience is not possible until mid-gestation. Although an active central nervous system is present by the eighth week of development and a brainstem by the end of the first trimester (which could act as a rudimentary modulator of sensory information and motor activity), Flower noted that the neocortex does not become a functional part of the neuraxis until at least mid-gestation when the thalamus (the major gateway for sensory input to the cerebrum) makes its first afferent contacts with the neocortex. Without the presence of a functional thalamic connection, Flower concludes that sentience is not possible.

While the cortical processing of pain theoretically becomes possible after development of the thalamo-cortical connections in the 26th week of gestation, noxious stimuli may trigger complex reflex reactions noted much earlier. Utilizing antibodies to detect small peptides known to be associated with painful stimuli neurotransmission, a number of investigators have suggested an earlier time frame for fetal sentience. Substance P, enkephalin, and neurofilament triplet proteins have all been found in this manner between 10 and 12 weeks of gestation (5). Although the relevance of these findings remains uncertain, Vanhatalo et al.  suggest that by triggering stress responses, the behavioral development of an individual at very early stages may be adversely affected. Hence, although it is not reasonable to speculate on the possible emotional experiences of pain in fetuses or premature babies, further work will need to assess the possible long term consequences of fetal sentience.

References:

1.  McCullagh P: Fetal sentience and fetal surgery. In: Adams AP, Cashman JN (eds.) Recent Advances in Anaesthesia and Analgesia. Edinburgh, Churchill Livingstone 1998; 107-21.
2.  Mahieu-Caputo D, Dommergues M, Muller F, Dumez Y. [Fetal pain]. Presse Med 2000;29(12):663-9
3.  Anand KJS, Hickey PR. Pain and its effects in the human neonate and fetus. N Engl J Med 1987;317:1321-9.
4.  Flower MJ. Neuromaturation of the human fetus. J Med Philos 1985;10(3):237-51
5.  Marti E, Gibson SJ, Polack JM, et al. Ontogeny of peptide and amine-containing neurones in motor, sensory, and autonomic regions of the rat and human spinal cord, dorsal root ganglia and rat skin. J Comp Neurol 1987;266:332-359.
6.  Vanhatalo S, van Nieuwenhuizen O. Fetal pain? Brain Dev 2000;22(3):145-50.


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