Multiple functional magnetic resonance imaging studies implicate the insula as a region of heightened neuronal activity in this condition. Since glutamate is a major cortical excitatory neurotransmitter Baicalein that functions in pain neurotransmission, we hypothesized that increased levels of insular Glu would be present in FM patients and that the concentration of this molecule would be correlated with pain report. Methods 19 FM patients and 14 age and sex matched pain free controls underwent pressure pain testing and a proton magnetic resonance spectroscopy session wherein the right anterior and right posterior insula were examined at rest. Results FM patients had significantly higher levels of Glu : FM 8. 09, HC 6. 86, p0. 009 and combined glutamate and glutamine : FM 12.38, HC 10. 59, p0. 001 within the right posterior insula as compared to controls. No differences were detected in any of the other major metabolites within this region and no group differences were detected for any metabolite within the right anterior insula. Within the right posterior insula, higher levels of Glu and Glx were associated with lower pressure BMS-707035 pain thresholds across both groups. Conclusion Enhanced glutamatergic neurotransmission resulting from higher concentrations of Glu within the posterior insula may play a role in the pathophysiology of FM and other central pain augmentation syndromes. Keywords fibromyalgia, glutamate, insula, pain, proton magnetic resonance spectroscopy Corresponding Author: Richard E.Harris, PhD Chronic Pain and Fatigue Research Center 24 Frank Lloyd Wright Drive PO Box 385, Lobby M Ann Arbor, MI 48106 Phone: 998 6996, Fax: 998 6900 Published in final edited form as: Arthritis Rheum. 2009 October, 60: 3146 3152. doi:10. 1002/art. 24849. Although acute pain can serve a beneficial function to alert an organism of immediate or imminent tissue damage, chronic pain can often occur in the absence of tissue damage or inflammation. Functional chronic pain syndromes are a subset of pain disorders wherein patients paradoxically report frequent pain symptoms in the absence of anatomical injury or objective pathological findings. As such these disorders are particularly troublesome for patients and clinicians alike. Although new treatment options exist, significant disability and dysfunction are prevalent.
Fibromyalgia is the prototypical functional chronic pain condition that afflicts approximately 2 4% of individuals. Although the etiology of this disorder remains largely unknown, emerging data suggests that FM arises through augmentation of central pain processing pathways. This hypothesis is based largely upon findings of previous functional neuroimaging studies showing that FM patients display augmented neuronal responses to both innocuous and painful stimuli, corroborating the allodynia and hyperalgesia seen in this condition. A growing body of literature suggests that glutamate, an excitatory neurotransmitter, within the central nervous system may play a role in FM pathology. A study by Peres et al. found that cerebrospinal fluid levels of Glu were elevated in FM patients possibly having consequences for glutamatergic neurotransmission. In a separate line of inquiry, the concentration of glutamine