This could result from adaptation due to the chronic presence of painful neuropathy of at least two years duration. Patients reported high scores in the chronic pain acceptance questionnaire and low scores in the pain catastrophizing questionnaire, which supports the hypothesis that reduction in BOLD fMRI response to acute heat-pain stimulation follows from long-term neuropathy-related pathophysiology. Previous studies have highlighted deactivation of the prefrontal cortex in response to pain in cluster headaches. Repetitive transcranial magnetic stimulation has also been linked to deactivation in capsaicin-induced pain. Activation in the right superior frontal gyrus has been previously reported in studies applying painful stimuli to healthy volunteers and activation in this area has been attributed to both the subjective experience of pain and other general unpleasant experiences. We identified regions that are known components of the brain��s pain matrix, during painful stimulation in both healthy volunteers and MM-CIPN patients. These functional areas are comparable to those found in other disease groups. There are numerous NSC727447 factors that may influence the overall invivo fMRI experiment. In the current ��box-car�� design, the BOLD effect is based on changes in MR signal between functional states, the source of which is assumed to be dominated by the net haemodynamic change linked to localised differences in synaptic and neuronal firing. It is not a direct measure of neuronal activity; rather it is an indirect physiological response. The 3-Methoxytyramine hydrochloride vascular coupling is currently not fully understood, particularly in the context of pathophysiology. One potential limitation of this study was that the median age of the MM-CIPN group was greater than that of the healthy volunteers. The reported influences of age on BOLD fMRI response for non-pain-specific studies appear complex including overall intracranial increases, increases in frontal regions and decreases in the anterior regions, all with increasing age. It must also be noted that chemotherapeutic agents themselves may alter vascular function and thus results should be interpreted in the light of these potential modulatory factors.