Evaluation of the effectiveness of pregabalin in alleviating pain associated with fibromyalgia: using functional magnetic resonance imaging study.

PurposeTo assess the efficacy of pregabalin by showing differences in the neuronal activities of fibromyalgia (FM) patients before and after longitudinal treatment using functional magnetic resonance imaging (fMRI).Materials and methodsIn total, 21 female patients with FM and 11 age- and gender-matched healthy controls participated. FM patients underwent fMRI at baseline and following pharmacological therapy with pregabalin to diminish their pain. Pressure-pain stimuli were delivered on the subject's thumbnail bed during fMRI scans. Brain activation regions in fMRI were evaluated for longitudinal changes using a paired t-test. Changes in clinical features were also assessed with the Fibromyalgia Impact Questionnaire (FIQ), Brief Fatigue Inventory (BFI), Beck Depression Inventory (BDI), Widespread Pain Index (WPI), Symptom Severity Scale Score (SSS), and State-Trait Anxiety Inventory (STAI).ResultsClinical scores were reduced significantly following therapy with five of the six clinical tests (FIQ, BFI, BDI, WPI, SSS; p ConclusionsOur findings confirm that pregabalin influences aspects of the whole pain matrix, using fMRI, inducing longitudinal changes in neuronal activity during the pain state, and that it reduces pain and other core symptoms of FM. This method could be applied to other longitudinal clinical trials of pharmacological treatments for FM

Modifying surface charge density of thermoplastic nanofluidic biosensors by multivalent cations within the slip plane of the electric double layer

Thermoplastic nanofluidic devices are promising platforms for sensing single biomolecules due to their mass fabrication capability. When the molecules are driven electrokinetically through nanofluidic networks, surface charges play a significant role in the molecular capture and transportation, especially when the thickness of the electrical double layer is close to the dimensions of the nanostructures in the device. Here, we used multivalent cations to alter the surface charge density of thermoplastic nanofluidic devices. The surface charge alteration was done by filling the device with a multivalent ionic solution, followed by withdrawal of the solution and replacing it with KCl for conductance measurement. A systematic study was performed using ionic solutions containing Mg and Al for nanochannels made of three polymers: poly(ethylene glycol) diacrylate (PEGDA), poly(methyl methacrylate) (PMMA) and cyclic olefin copolymer (COC). Overall, multivalent cations within the slip plane decreased the effective surface charge density of the device surface and the reduction rate increased with the cation valency, cation concentration and the surface charge density of thermoplastic substrates. We demonstrated that a 10-nm diameter in-plane nanopore formed in COC allowed translocation of -DNA molecules after Al modification, which is attributed to the deceased viscous drag force in the nanopore by the decreased surface charge density. This work provides a general method to manipulate surface charge density of nanofluidic devices for biomolecule resistive pulse sensing. Additionally, the experimental results support ion-ion correlations as the origin of charge inversion over specific chemical adsorption

Commonly activated regions in FM patients and healthy control.

<p>Yellow clusters indicate common regions activated by painful stimuli in FM patients and healthy controls. Common regions include bilateral cerebellum, contralateral supramarginal gyrus, IFG and MFG.</p

Pain-stimulation paradigm of the fMRI scan.

<p>Pain-stimulation paradigm of the fMRI scan.</p

Comparison between responders and non-responders according to medication therapy.

<p>Regions including bilateral fusiform, ipsilateral IPL and contralateral STG were more activated in responders.</p

Statistical comparisons of clinical scores.

<p>(Mean and SD.) (A) FM patients and healthy controls (B) pre-treatment group and post-treatment group. Fibromyalgia Impact Questionnaire (FIQ), Brief Fatigue Inventory (BFI), Beck Depression Inventory (BDI), Widespread Pain Index (WPI), Symptom Severity Scale score (SSS), and State-Trait Anxiety Inventory (STAI). * <i>p</i> < 0.05, ** <i>p</i> < 0.01.</p

Commonly activated regions in pre-treatment and post-treatment.

<p>Functional magnetic resonance images showing activation in two regions, the supramarginal gyrus (arrow in left image) and inferior frontal gyrus (arrow in right image), during pressure-pain stimulation of subjectively strong intensity at both pre-treatment (yellow) and post-treatment (red) in the responder subgroup of FM patients.</p

Outline of the study design and classification of subjects used for evaluation of the effectiveness of pregabalin in the treatment of patients with fibromyalgia, using fMRI.

<p>Outline of the study design and classification of subjects used for evaluation of the effectiveness of pregabalin in the treatment of patients with fibromyalgia, using fMRI.</p

Comparison between FM patients and healthy controls.

<p>Augmented brain activation regions in FM patients compared with healthy controls resulting from the same level of subjective pain intensity (GBS level 14). Regions are Bilateral Supramarginal gyrus, ipsilateral cerebellum, contralateral calcarine, STG, IFG, thalamus and insula.</p

Comparison between pre-treatment and post-treatment.

<p>Coronal view of functional magnetic resonance images showing activation regions with significantly increased BOLD signals at pre- <i>versus</i> post-treatment in the responder subgroup of FM patients. In bilateral thalamus, IPL, contralateral precuneus, calcarine and ipsilateral insula, BOLD signal of pre-treatment was greater than post-treatment.</p