The effect of eugenol on GABA-induced currents in HEK 293 cells with GABA receptors.

<p>Eugenol (500 μM) blocked the GABA (20 μM)-induced current. This blocking was observed in both the L- and S-forms of the GABA_A receptor (*p < 0.05). Data are expressed as mean ± SEM.</p

Dose-response curve for eugenol action on GABA-induced currents in HEK 293 cells with GABA receptors.

<p>Eugenol (50, 100, 300, 500, 1000, and 2000 μM) blocked the GABA (20 μM)-induced current in a dose-dependent manner. This blocking effect of eugenol on GABA-induced current was observed in HEK 293 cells transfected with the L- or S-form of the GABA_A receptor. Data are expressed as mean 00B1 SEM.</p

The effect of eugenol on GABA-induced currents in trigeminal ganglion neurons.

<p>(A) Eugenol (1 mM) abolished the GABA (500 μM)-induced current in TG neurons; the current recovered to the control value after washout of eugenol (*p < 0.05). (B) The γ2 subunit of the GABA_A receptor was expressed in TG neurons. Data are expressed as mean ± SEM.</p

The effect of eugenol on GABA-induced currents in HEK 293 cells expressing GABA receptors was independent of G-protein activation.

<p>Eugenol (1 mM) blocked the GABA (20 μM)-induced current in HEK 293 cells transfected with the L- or S-form of the GABA_A receptors in the presence of 100 μM GDP-βS (*p < 0.05). Data are expressed as mean ± SEM.</p

Non-competitive blocking effect of eugenol on GABA-induced currents in HEK 293 cells expressing GABA receptors.

<p>Eugenol (500 μM) blocked the GABA (20, 200, 1000 μM)-induced current. This blocking was similar for L- and S-forms of the GABA_A receptor (p < 0.05 compared to each GABA concentration). Data are expressed as mean ± SEM.</p

Impaired insula functional connectivity associated with persistent pain perception in patients with complex regional pain syndrome

<div><p>Given that the insula plays a contributory role in the perception of chronic pain, we examined the resting-state functional connectivity between the insular cortex and other brain regions to investigate neural underpinnings of persisting perception of background pain in patients with complex regional pain syndrome (CRPS). A total of 25 patients with CRPS and 25 matched healthy controls underwent functional magnetic resonance imaging at rest. With the anterior and posterior insular cortices as seed regions, we compared the strength of the resting-state functional connectivity between the two groups. Functional connectivity between the anterior and posterior insular cortices and the postcentral and inferior frontal gyri, cingulate cortices was reduced in patients with CRPS compared with controls. Additionally, greater reductions in functional connectivity between the anterior insula and right postcentral gyrus were associated with more severe sensory pain in patients with CRPS (short-form McGill Pain Questionnaire sensory subscores, <i>r</i> = -.517, <i>P</i> = .023). The present results imply a possible role of the insula in aberrant processing of pain information in patients with CRPS. The findings suggest that a functional derangement of the connection between one of the somatosensory cortical functions of perception and one of the insular functions of awareness can play a significant role in the persistent experience of regional pain that is not confined to a specific nerve territory.</p></div

Scatter plots showing the correlations of functional connectivity in the anterior insula and right postcentral gyrus with (A) pain severity and (B) illness duration.

<p>Abbreviations: MPQ, McGill Pain Questionnaire.</p

Resting state functional connectivity networks of the anterior insula.

<p>(A) Functional connectivity patterns in healthy controls and (B) patients with CRPS (FDR < 0.01, within-group analysis). (C) Brain areas showing a significant reduction in anterior insula functional connectivity in patients with CRPS relative to healthy controls (<i>P</i> < 0.005 for permutation test, between-group analysis).</p

Brain regions showing decreased functional connectivity with the anterior and posterior insular cortices in patients with CRPS relative to healthy control subjects.

<p>Brain regions showing decreased functional connectivity with the anterior and posterior insular cortices in patients with CRPS relative to healthy control subjects.</p

Demographic and clinical characteristics of the study participants.

<p>Demographic and clinical characteristics of the study participants.</p