Functional imaging of pain.

Brain functional imaging has been applied to the study of pain since 1991. Then, a plethora of studies around the world looking at pain sensations and their brain correlates was published. Four kinds of studies can be distinguished: i) A first set investigated brain responses to noxious heat stimulations (above the pain threshold) relative to an equivalent warm innocuous stimulation (below the pain threshold). The aim of these studies was to identify the pattern of brain regions involved in the nociceptive processes and they may be considered as descriptive studies rather than explanative studies. Their value was to list for the first time every brain structure that might be playing a role. ii) Secondly, several experimental investigations have explored brain activations when subjects are confronted with unpleasant situations such as seeing or imagining other people in pain (e.g. empathy for pain). Obviously, feeling pain and representing others suffering share a common brain network, indicating that a large part of the regions showing intensity changes are not specific to nociception. iii) The third set of imaging studies is aimed at investigating the functional and structural brain abnormalities that may account for clinical pain states. Unfortunately, a relatively small number of studies provide clear findings that do not allow drawing convincing and generalized conclusions. iv) The last set of studies focused on the modulation of pain experience in humans. Several research groups conducted projects on different factors known to alter pain perception and their associated brain processes with the objective of identifying one or more key regions capable of controlling the pain sensation. In the same vein, investigations have been performed around pain therapies. From the clinician's point of view, it may be seen as complementary to assess pain and analgesic processes. All these aspects of pain research with functional imaging are considered below, including attempts to understand the functional significance of each of the observed activations. v) A special focus will be dedicated to new sophisticated approaches, vi) applied to neuroimaging (e.g. graph theory). These promising techniques and recent electrophysiological investigations bring additional information to our understanding of pain/analgesic processes, particularly for temporal dynamics and connectivity between brain regions.