Evaluation of the Effectiveness of Pregabalin in Alleviating Pain Associated with Fibromyalgia: Using Functional Magnetic Resonance Imaging Study

Kim, Seongho; Lee, Young-Ho; Lee, Soo Kon; Mun, Chi-Woong

doi:10.1371/journal.pone.0074099

Cited by 24 publications

(23 citation statements)

References 30 publications

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“…PGB is believed to reduce the magnitude of the enhanced pronociception process in FMS (Crofford et al, 2005;Arnold et al, 2008;Mease et al, 2008). Imaging studies using fMRI confirmed that PGB connects neuronal connectivity and biochemical aspects of pain in FMS (Harris et al, 2013;Kim et al, 2013).…”

Section: Treatmentmentioning

confidence: 81%

Fibromyalgia Syndrome in Need of Effective Treatments

Theoharides

Tsilioni

Arbetman

et al. 2015

J Pharmacol Exp Ther

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Fibromyalgia syndrome (FMS) is a chronic, idiopathic condition of widespread musculoskeletal pain, affecting primarily women. It is clinically characterized by chronic, nonarticular pain and a heightened response to pressure along with sleep disturbances, fatigue, bowel and bladder abnormalities, and cognitive dysfunction. The diagnostic criteria have changed repeatedly, and there is neither a definitive pathogenesis nor reliable diagnostic or prognostic biomarkers. Clinical and laboratory studies have provided evidence of altered central pain pathways. Recent evidence suggests the involvement of neuroinflammation with stress peptides triggering the release of neurosenzitizing mediators. The management of FMS requires a multidimensional approach including patient education, behavioral therapy, exercise, and pain management. Here we review recent data on the pathogenesis and propose new directions for research and treatment.

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Section: Treatmentmentioning

confidence: 81%

Fibromyalgia Syndrome in Need of Effective Treatments

Theoharides

Tsilioni

Arbetman

et al. 2015

J Pharmacol Exp Ther

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“…A pharmacological study in FM demonstrates the fallacy of incomplete evidence [180]. The study recruited 21 FM patients to undergo treatment with pregabalin, measuring BOLD activity evoked by blunt pressure before and after treatment.…”

Section: Selection Bias and The Fallacy Of Incomplete Evidencementioning

confidence: 99%

“…This treatment effect correlated with increased BOLD activity to pellet-pain stimulation in the pINS and contralateral S1. An open-label study of routine clinical treatment with pregabalin compared the pain evoked BOLD activity of responders (n=9) to that of non-responders (n=10) [180]. Responders had increased BOLD activity in the bilateral fusiform, ipsilateral IPL, and contralateral superior TC.…”

Section: Neuroimaging the Treatment Effect In Fibromyalgiamentioning

confidence: 99%

Neuroimaging of Central Sensitivity Syndromes: Key Insights from the Scientific Literature

Walitt

Čeko²,

Gracely³

et al. 2016

CRR

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Central sensitivity syndromes are characterized by distressing symptoms, such as pain and fatigue, in the absence of clinically obvious pathology. The scientific underpinnings of these disorders are not currently known. Modern neuroimaging techniques promise new insights into mechanisms mediating these postulated syndromes. We review the results of neuroimaging applied to five central sensitivity syndromes: fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular joint disorder, and vulvodynia syndrome. Neuroimaging studies of basal metabolism, anatomic constitution, molecular constituents, evoked neural activity, and treatment effect are compared across all of these syndromes. Evoked sensory paradigms reveal sensory augmentation to both painful and non-painful stimulation. This is a transformative observation for these syndromes, which were historically considered to be completely of hysterical or feigned in origin. However, whether sensory augmentation represents the cause of these syndromes, a predisposing factor, an endophenotype, or an epiphenomenon cannot be discerned from the current literature. Further, the result from cross-sectional neuroimaging studies of basal activity, anatomy, and molecular constituency are extremely heterogeneous within and between the syndromes. A defining neuroimaging “signature” cannot be discerned for any of the particular syndromes or for an over-arching central sensitization mechanism common to all of the syndromes. Several issues confound initial attempts to meaningfully measure treatment effects in these syndromes. At this time, the existence of “central sensitivity syndromes” is based more soundly on clinical and epidemiological evidence. A coherent picture of a “central sensitization” mechanism that bridges across all of these syndromes does not emerge from the existing scientific evidence.

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“…Prior studies analyzing the effects of PGB have shown that treatment reduced both insular activity(41), and insula-DMN connectivity was related to decreased clinical pain (13). The decreased pro-nociceptive evoked-pain connectivity between the posterior insula–anterior insula in analyses 3 and 4 and posterior insula–thalamus in analysis 3 are consistent with these findings and extend them to connectivity differences during an evoked-pain state.…”

Section: Discussionmentioning

confidence: 99%

Association of Alterations in Gray Matter Volume With Reduced Evoked‐Pain Connectivity Following Short‐Term Administration of Pregabalin in Patients With Fibromyalgia

Puiu

Kairys

Pauer

et al. 2016

Arthritis & Rheumatology

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Objective; Pregabalin (PGB) is an α2β 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. Methods 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. Results 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. Conclusion Short-term PGB treatment alters brain structure and evoked-pain connectivity, and these decreases were associated with reduced clinical 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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Evaluation of the Effectiveness of Pregabalin in Alleviating Pain Associated with Fibromyalgia: Using Functional Magnetic Resonance Imaging Study

Cited by 24 publications

References 30 publications

Fibromyalgia Syndrome in Need of Effective Treatments

Fibromyalgia Syndrome in Need of Effective Treatments

Neuroimaging of Central Sensitivity Syndromes: Key Insights from the Scientific Literature

Association of Alterations in Gray Matter Volume With Reduced Evoked‐Pain Connectivity Following Short‐Term Administration of Pregabalin in Patients With Fibromyalgia

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