Alterations in Gray Matter Volume are Associated with Reduced Evoked-Pain Connectivity following Acute Pregabalin Administration

Associated faculty or student(s): Publication Date:
Wednesday, January 27, 2016


Pregabalin (PGB) is an α2δ calcium channel subunit ligand that has previously been shown to reduce chronic pain in multiple conditions. Preclinical studies indicate that PGB may down-regulate brain glutamate release while also inhibiting astrocyte induction of glutamatergic synapse formation. Recent clinical research supports PGB modulating glutamatergic activity and functional brain connectivity in order to produce analgesia. However, no studies have examined concurrent changes in brain gray matter volume (GMV) or evoked-pain connectivity in humans receiving PGB.


Sixteen female fibromyalgia patients completed a randomized double-blind two-period cross-over study of PGB versus placebo (PBO). Before and after each period, patients had high-resolution structural and evoked pressure-pain functional brain imaging. GMV was analyzed using voxel-based morphometry, and functional connectivity during evoked pressure-pain was also assessed.


PGB administration significantly reduced GMV within the posterior insula bilaterally, whereas there were no significant changes in insular GMV following PBO treatment. GMV reductions were also observed when comparing PGB versus PBO treatment in the medial frontal gyrus, which were associated with reduced clinical pain. These reductions in insular GMV were associated with concomitant reductions in connectivity to the default mode network (DMN), which was also associated with reduced clinical pain.


Short-term PGB treatment alters brain structure and evoked-pain connectivity, and these decreases were associated with reducedclinical pain. We speculate that these fairly rapid changes in GMV may be related to brain neuroplasticity. It is unknown if these effects are generalizable to other chronic pain states.

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