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Even the most premature neonate has the neural pathways to respond to noxious stimuli. The development of pain pathways in earlier fetal life has been the subject of histological study and speculation.
Primary afferent nerve fibres innervate the skin of a fetus from seven weeks gestation. Projection neurones from the dorsal horn of the spinal cord reach the thalamus at about this time also. Neural projections from the thalamus to the cortex first appear between 12 and 16 weeks but mature synaptic connections to cortical neurones only become evident from 23 weeks onwards. Characteristic layering of thalamic and cortical neurones is evident from about 26 weeks gestation. In parallel with this, peripheral noxious stimulation is able to evoke cortical responses in premature babies from a gestational age of 25 weeks.
As all the above suggests, ascending pathways appear to be present and functional by 25 weeks gestation. In contrast, descending (often inhibitory) pathways tend to mature more slowly and may not mature until mid-infancy. Theoretically at least, this implies that responses to noxious stimuli in neonates and in early infancy will tend to be exaggerated and generalised.
While anatomical and electrophysiological evidence confirms that biological systems necessary for nociception are intact and functional from 26 weeks gestation, inferences regarding fetal pain are limited. The conscious experience of pain requires cognitive, affective and evaluative experiences that the limited neural system and environment of the fetus cannot support.
In contrast to the protected environment of the womb (in which a fetus is buffered from environmental stimuli and continuously exposed to the narcotic effects of progesterone), postnatal life brings intense afferent stimulation and wakefulness. With this comes the possibility of psychological processes involving content derived from the environment (objects, people and symbols) and the experience of pain.
Even if the experience of pain is difficult to ascertain in preverbal children, a graded hormonal response to surgical intervention has been well documented in neonates (including ex-premature neonates) confirming that the hypothalamo-pituitary-adrenal axis responds in a similar fashion to adult counterparts. Actively managing this response with adequate perioperative analgesia has been shown to reduce both morbidity and mortality in infants undergoing surgery.
Apart from the obvious ethical considerations mandating analgesia for infants and children, the reduction in morbidity and mortality remains a strong argument in favour of aggressive pain management in all children. Many would argue also that early pain experiences may adversely affect pain processing in later life. Although some evidence exists suggesting that early pain experiences can influence pain responses in later development, this question remains in need of definitive data describing clinically significant long-term outcomes. Notwithstanding this gap in scientific knowledge, there remains no valid argument to withhold appropriate analgesia from neonates, infants and children.
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