Due to the progress in fetal surgery, it is important to acquire data about fetal pain.
Material and methods: We performed a Medline research from 1995, matching the following key words: "pain" and "fetus", with the following: "subplate", "thalamocortical", "myelination", "analgesia", "anesthesia", "brain", "behavioral states", "substance p". We focused on: (a) fetal development of nociceptive pathways; (b) fetal electrophysiological, endocrinological and behavioral reactions to stimuli and pain.
Results: We retrieved 217 papers of which 157 were highly informative; some reported similar data or were only case-reports, and were not quoted. Most endocrinological, behavioral and electrophysiological studies of fetal pain are performed in the third trimester, and they seem to agree that the fetus in the 3rd trimester can experience pain. But the presence of fetal pain in the 2nd trimester is less evident. In favor of a 2nd trimester perception of pain is the early development of spino-thalamic pathways (approximately from the 20th week), and the connections of the thalamus with the subplate (approximately from the 23rd week). Against this possibility, some authors report the immaturity of the cortex with the consequent lack of awareness, and the almost continuous state of sleep of the fetus.
Conclusions: Most studies disclose the possibility of fetal pain in the third trimester of gestation. This evidence becomes weaker before this date, though we cannot exclude its increasing presence since the beginning of the second half of the gestation.