Background/Purpose: Central pain augmentation resulting from enhanced excitatory and/or decreased inhibitory neurotransmission is a proposed mechanism underlying the pathophysiology of functional pain syndromes such as fibromyalgia (FM). Previously, we demonstrated that glutamate (Glu), an excitatory neurotransmitter, and combined Glu and glutamine (Glx) levels are higher within the posterior insula of patients with FM [Harris et al. AnR 2009]. Moreover we also found that reduction in the levels of posterior insula Glx and Glu, following a non-pharmacologic intervention, were also associated with decreased pain [Harris et al. AnR 2008].  Here we sought to replicate these findings in a separate sample of FM patients within the placebo arm of a randomized crossover trial of milnacipran versus placebo. 

Methods: Thirteen female individuals (mean age 41.8 yrs, SD = 11.0) satisfying 1990 American College of Rheumatology criteria for FM completed a randomized double-blind two-period cross-over study of milnacipran versus placebo. For the purposes of this analysis, only the placebo periods were studied.  Each 7-week period (drug or placebo) was followed by a 14 day taper and washout.  Prior to and following each period, proton magnetic resonance spectroscopy (¹H-MRS) of the right posterior insula was acquired for each patient at rest.  Individual patient spectra were fit with the Linear Combination Model program and the levels of Glx were estimated relative to levels of creatine (Cr) (i.e. Glx/Cr ratio).  Immediately prior to each ¹H-MRS scan, evoked pressure-pain was delivered to the left thumbnail bed during a functional magnetic resonance imaging (fMRI) run (fMRI data not presented here). Subjects reported their “average pain”, during this fMRI run, using a numerical rating scale (0-100; 0=no pain and 100=worst pain imaginable) following each session.  This pressure pain rating was correlated with Glx levels.

Results: Cross sectional analysis, prior to placebo administration, demonstrated that Glx/Cr levels were positively related to subjective pain report during evoked pressure pain (r = 0.811, p < 0.001): higher Glx/Cr was associated with greater pain.  Moreover the change in Glx/Cr from pre- to post-placebo was also positively correlated with the change in evoked pain report (r = 0.697, p = 0.008): reductions in Glx/Cr were associated with reductions in pain.  Glx changes were not related to clinical pain (p < 0.05).

Conclusion: Similar to our previous findings, concentrations of Glx within the right posterior insula were found to be positively correlated with pain report in both cross-sectional and longitudinal analyses. These results add to the growing body of literature indicating that ¹H-MRS derived levels of Glx may serve as a marker or surrogate end point for clinical trials of FM.  Replication of these findings in other pain states is recommended.

References: Harris et al. AnR 2008

---

« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/posterior-insula-combined-glutamate-and-glutamine-is-associated-with-pain-in-fibromyalgia-a-replication-study/