Further, medium pressure pain threshold was negatively associated with each of the outcomes. No significant group X pressure pain interaction term was detected for either model and for this reason the interaction term was not included in the final models. Similar results were obtained in analyses using weighted least BCR-ABL Signaling Pathway squares. Similar effects were also obtained when using general linear models with the high pressure threshold. Overall these data indicate that FM patients have elevated Glu and Glx levels within the posterior insula and that these levels are associated with pressure pain thresholds. Since there was no significant group X pressure threshold interaction term, the relationship between Glu and Glx levels and pain threshold was similar across groups.
Although the relationship was similar it was shifted towards higher metabolite levels for the patient group. Discussion These findings point towards a potential role of insular Glu in the pathophysiology of fibromyalgia. The levels of glutamate in the posterior insula were higher for individuals with FM as compared Resveratrol to controls, and the levels of glutamate were negatively correlated with pressure pain thresholds. This suggests that the left ward shift in the stimulus response function seen in both experimental pain testing and functional imaging in FM is associated with higher levels of glutamate in certain brain regions involved in pain processing, such as the posterior insula. The posterior insula is known to play a prominent role in pain and interoceptive sensory processing, whereas the anterior insula is involved in the affective processing of pain and other subjective feelings.
Since the levels of Glu in the anterior insula were no different in the FM group, this could suggest that a component of this disorder involves an amplification in sensory but not affective processing. Our findings are entirely consistent with the broader literature and knowledge regarding FM and related syndromes, which suggests that individuals with these conditions are at the far right end of the bell shaped curve of pain and sensory processing in the population. Our data suggest that glutamate is playing a role in this augmented pain processing, in those individuals who have elevated glutamate. Since greater Glu was associated with lower pain thresholds, this suggests that Glu in the posterior insula is related to pain processing.
The elevated levels of Glu in the FM group could raise the set point of baseline neural activity in this region which could result in augmented responses to painful stimuli. In a related line of inquiry, cold pain has been shown to increase Glu within the cingulate of pain free controls. FM patients may have more glutamate within their synaptic vesicles, higher numbers or densities of glutamatergic synapses, or even less uptake of glutamate from the synaptic cleft. Any of these changes would be consistent with the hypothesis that there is augmentation of Harris et al. Page 5 Arthritis Rheum. Author manuscript, available in PMC 2010 October 1. pain and sensory processing in FM. If true, this aspect of the pathophysiology of FM may be more similar to conditions such as epilepsy or neurodegenerative diseases than to the rheumatic syndromes which it has historically been associate