For example, in epilepsy cortical and sub cortical neurons appear to be hyper excitable as a result of Bergenin elevated concentrations of glutamate. These clusters of excited neurons are thought to form a locus of heightened activity which can then initiate a spreading wave of action potentials which propagate to other connected brain regions. FM may simply represent a condition wherein glutamatergic hyperactivity occurs within brain regions devoted to processing and modulating pain. This could arise from local increases in Glu or enhanced ascending activity to this area. This hypothesis is consistent with the fact that one of the FDA approved medications for FM is pregabalin, a drug whose action is thought to involve inhibition of presynaptic glutamate release.
Interestingly this drug is also used in the treatment of epilepsy. AS-605240 As with any trial, our study has limitations. The voxels used during H MRS include multiple cell types. Our metabolite estimates of Glu and Glx reflect an ensemble average of all cell types within the tissue samples. As such our findings must be interpreted with the knowledge that the cellular and sub cellular location of the elevated glutamate is unknown. That said our methods have been empirically validated by other reported single voxel spectroscopy studies indicating that this approach is state of the art for non invasive assessment of molecular concentrations within the brain. We also recognize that our findings pertain only to the insula. Future studies that detect Glu levels in other pain processing structures such as the secondary somatosensory cortex, amygdala, cingulate etc.
are needed to determine the spatial extent of elevated Glu levels. Of note a recent H MRS study has shown decreased NAA within the hippocampus of individuals with FM whereas we observed increased NAA in the posterior insula albeit at the trend level. In addition, our patient population excluded individuals with current major depression. It is possible that Glu levels within the anterior insula of depressed FM patients might be elevated, since it is known that the anterior insula is more involved in emotional processing of sensory information. Thus, our lack of group differences in anterior insula Glu may be due to the absence of depression in our sample. Finally although our results are significant, they originate from a relatively small number of participants.
Validation of these findings from other studies could be made with larger study populations. Overall we find that glutamate within the posterior insula is a potential pathologic factor in FM. The previously observed allodynia and hyperalgesia seen in these patients may be due to elevated excitatory glutamatergic neurotransmission within the posterior insula. Future studies are needed to confirm whether these findings are observed in other functional pain syndromes. Supplementary Material Refer to Web version on PubMed Central for supplementary material. The dorsal side up body posture of standing quadrupeds is maintained by coordinated activity of all limbs. Somatosensory input fromthe limbs evokes postural responseswhen the supporting surface is perturbed. The aim of this study was to reveal the contribution of sensory inputs from individual limbs to the posture related modulati