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Author's note: Last week we discussed the issue of fetal sentience. Today we'll continue on that topic.
1.  Is the cerebral cortex necessary to experience "pain"?
2.  Can an anencephalic fetus experience "pain"?

1. “疼痛”体验是否必须有大脑皮层的参与？
2.  无脑畸形的胎儿能感受到“疼痛”吗？

参考答案：

1.“疼痛”体验是否必须有大脑皮层的参与？

完整成熟的大脑皮质有感受疼痛的基本特点，但是该理论因在有明显皮层损伤或半球切除术的患者存在持续感觉而受到挑战[1]。最近的研究表明皮层下通路具有对伤害性刺激进行处理和反应的能力[1]。

然而，皮层在疼痛处理过程中并非无目的性。Price[2]最近的综述表明，皮层在疼痛的感觉尺度（与即将出现的作用相关的不愉快的情感感受，术语为副作用）方面非常重要。他对实验和临床研究综述发现，大脑结构之间的相互作用在伤害性疼痛的处理过程中很重要。研究表明，到边缘结构和内侧丘脑核的脊髓通路可直接输入与情感反应有关的信号进入大脑。此外，皮质-边缘通路整合伤害性刺激输入并使之成为记忆，以起到影响疼痛的认知调停作用。直接和皮质-边缘通路集中于相同的带状前回和皮层下结构，其功能为引起情感和优先反应。

最近进行的脑地形图分析系统技术，包括功能性磁共振成象（MRI）和正电子发射断层扫描术（PET），证实了不同刺激反应性间的差异，表明皮层为疼痛形成过程的一个有效部分。Apkarian等[3]通过对健康志愿者使用fMRI，证实给与两个不同的热刺激后皮层活动方式的差异。7例右利手的受试者右手指涂抹1,074mm²或21 mm²大小的刺激剂。给与适宜疼痛范围的刺激温度，结果表明，fMRI信号（与脑组织容积大小一致）的大小与刺激的大小一致。

这些结果与早期研究综合表明，对伤害性刺激的不良应激反应可能完全是皮层下的，然而，对疼痛鉴别的良好判断和情感性加重在局部可能为皮层水平。

2.无脑畸形的胎儿能感受到“疼痛”吗？

皮层的组成可能在情感编码或定位上更重要，无脑畸形的婴儿或胎儿可有对不愉快感受刺激产生反应的能力。Van Assche[4]确信，有功能性的下丘脑一垂体神经内分泌系统的无脑畸形胎儿应具有感受疼痛的能力。因为在健康成人中观察到的及与疼痛相关的其他生理反应也在无脑畸形的婴儿中观察[5]，应对这些情感的生理和深层次意义进行更一步研究。

Is the cerebral cortex necessary to experience "pain"?

The essential nature of an intact, mature cerebral cortex to experience pain has been challenged by the persistence of the sensation in patients with significant cortical lesions and/or with surgical removal of an entire hemisphere (1). In addition, many investigations to date implicate subcortical pathways for the processing and response to nociceptive stimuli (1).

However, the cortex is not without purpose in pain processing. Price (2) in a recent review, noted that the cortex is particularly important in the affective dimension of pain (feelings of unpleasantness and emotions associated with future implications, termed secondary affect). His review of experimental and clinical studies demonstrated that interactions with brain structures were important for the processing of nociceptive information. Spinal pathways to limbic structures and medial thalamic nuclei were noted to provide direct input to brain areas involved in affective responses. In addition, cortico-limbic pathways integrated nociceptive input with contextual information and memory to provide cognitive mediation of pain affect. Both direct and cortico-limbic pathways converge on the same anterior cingulate cortical and subcortical structures whose function may be to establish emotional and response priorities.

Recent work with brain mapping technologies, including functional magnetic resonance imaging (MRI) and positron emission tomography (PET), have also demonstrated differences in responses to various stimuli, suggesting that the cortex is an active part of pain processing. Apkarian et al. (3) demonstrated differences in cortical activity patterns to two different thermal stimuli in normal volunteers using functional magnetic resonance imaging (fMRI). Seven right-handed subjects had their right hand fingers covered either 1,074-mm(2)-area large stimulator or 21-mm(2)-area small stimulator. With stimulus temperatures in the moderately painful range, greater and smaller fMRI signals (consistent with larger and smaller brain tissue volumes) were noted with larger and smaller stimuli, respectively.

These results, combined with earlier work, suggest that a distress response to a noxious stimuli may be almost entirely subcortical, however, the finer discrimination and emotional overlay of this painful appreciation may be cortical in location (1).

Can an anencephalic fetus experience "pain"?

As cortical components appear more important for the emotional encoding or distinct localization, anencephalic infants/fetuses may have the capacity for reacting to unpleasant sensory stimuli. Van Assche et al. (4) convincingly argue that an anencephalic fetus with a functional hypothalamohypophysial system should be able to appreciate pain. As other physiologic responses that are observed in healthy adults and associated with pain are also observed in anencephalic infants (5), further research into the physiology and the implications of these findings will have to be done.

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.  Price DD. Psychological and neural mechanisms of the affective dimension of pain. Science 2000;288(5472):1769-72
3.  Apkarian AV, Gelnar PA, Krauss BR, Szeverenyi NM. Cortical responses to thermal pain depend on stimulus size: a functional MRI study. J Neurophysiol 2000 May;83(5):3113-22.
4.  Van Assche FA. Anencephalics as organ donors. Am J Obstet Gynec 1990;163:599-600.
5.  Jahnukainen T, Lindqvist A, Aarimaa T, et al. Reactivity of skin blood flow and heart rate to external thermal stimulation in anencephaly. Acta Paediatr 1997;86(4):426-7.


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