Cingulate-mediated approaches to treating chronic pain.

Anterior midcingulate cortex (aMCC) has been shown to be involved in most of the functional imaging studies investigating acute pain. For 10-15 years, it has even been a main focus of interest for pain studies, considering that neurons in the aMCC could encode for pain intensity. This latter function is now presumed to occur in secondary somatosensory (SII) area and/or insular cortices, while anterior cingulate cortex (ACC) is supposed to sustain other functions such as pain-related attention, arousal, motor withdrawal reflex, pain modulations, and engagement of endogenous pain control system. The quantitative imaging studies have shown a rich density of opioid receptors in the ACC. Thus, the perigenual subdivision has been suggested to participate in top-down controls of pain, (including the placebo effects known to be opioid mediated), mainly (but not exclusively) through the connection between the orbitofrontal/subgenual ACC and the periaqueductal gray (PAG). From this rationale, this area may lead to neurosurgical targeting including electrical stimulation for intractable pain in the future. A number of imaging studies have also reported activity changes in the posterior cingulate cortex during pain and proposed its speculative involvement to modulate the conscious experience of pain according to elements from the context and awareness of the self and others.