Abnormal activation of brain regions in idiopathic trigeminal neuralgia patients by fMRI: An activation likelihood estimation meta-analysis.

BACKGROUND: Idiopathic trigeminal neuralgia (ITN) is one of the most common types of neuropathic pain, severely affecting the physiological and psychological wellbeing of patients. Recently, fMRI has been used to examine abnormal activation of brain regions in patients with ITN. However, sample sizes have been small in these few studies, and the abnormally activated brain regions remain unclear. Therefore, in the present study, we retrieved and analyzed literature on the brain areas with abnormal or reduced activation in ITN patients, with the aim of providing insight into the neuropathological basis of the disease and to provide new targets for treatment. METHODS: We retrieved resting state fMRI studies on trigeminal neuralgia patients from PubMed, the Web of Science and Scopus databases until November 2022, and we extracted the coordinates of the sites with increased or decreased activation. We used activation likelihood estimation (ALE) meta-analysis to identify regions of abnormal activation in ITN patients. RESULTS: ALE meta-analysis revealed that the left caudate nucleus and right anterior ventral nucleus of the thalamus are abnormally hyperactivated in ITN patients. Moreover, ITN patients showed reduced activation in the left precuneus, middle temporal gyrus, lingual gyrus, and medial frontal gyrus. CONCLUSION: ALE meta-analysis identified several brain regions with abnormally high or decreased activation in ITN patients. Sites with altered activation may be potential targets for non-invasive brain stimulation as adjunct therapy for ITN.

Role of Ras, ERK, and Akt in glucocorticoid-induced differentiation of embryonic rat somatotropes in vitro.

This study investigated the roles of Ras, ERK, and Akt in the glucocorticoid-induced differentiation of growth hormone-producing pituitary cells in vitro. Pituicytes isolated from day-18 rat embryos were cultured with 50 mM dexamethasone in addition to specific inhibitors of Ras (manumycin; 0.5, 5, 50 nM), ERK (U0126, 10 µM), or Akt (LY294002, 25 µM). Differentiation was assessed using immunofluorescent staining of intracellular growth hormone. Radioimmunoassay and Western blot analyses were used to determine levels of secreted and intracellular growth hormone, respectively. Manumycin reduced the fraction of growth hormone-positive cells and dexamethasone-induced growth hormone secretion in a dose-dependent manner (both P < 0.001). In the absence of dexamethasone, LY294002 and U0126 did not alter the fraction of growth hormone-positive cells or intracellular growth hormone protein expression or secretion. Both LY294002 and U0126 alone significantly attenuated the fraction of dexamethasone-treated GH-positive cells and the secretion of GH compared to those of cells treated only with dexamethasone (50 nM for 44 h or 48 h) (all P < 0.05). Dexamethasone treatment alone did not change GH protein levels. Treatment of cells with a combination of LY294402 and U0126 significantly attenuated the fraction of dexamethasone-treated GH-positive cells, GH protein levels, and GH secretion compared to cells treated with dexamethasone alone (all P < 0.05). Moreover, dexamethasone-induced phosphorylation of GTP-Ras, ERK, and Akt was significantly attenuated by exposure to the respective inhibitors (P < 0.05). Taken together, our results indicate that Ras, ERK, and Akt are key effectors in the glucocorticoid-induced differentiation of growth hormone-secreting cells.