Ketamine is an important analgesia clinically used for both acute and chronic pain. The acute analgesic effects of ketamine are generally believed to be mediated by the inhibition of NMDA receptors in nociceptive neurons. However, the inhibition of neuronal NMDA receptors cannot fully account for its potent analgesic effects on chronic pain because there is a significant discrepancy between their potencies. The possible effect of ketamine on spinal microglia was first examined because hyperactivation of spinal microglia after nerve injury contributes to neuropathic pain. Optically pure S-ketamine preferentially suppressed the nerve injury-induced development of tactile allodynia and hyperactivation of spinal microglia. S-Ketamine also preferentially inhibited hyperactivation of cultured microglia after treatment with lipopolysaccharide, ATP, or lysophosphatidic acid. We next focused our attention on the Ca 2ϩ -activated K ϩ (K Ca ) currents in microglia, which are known to induce their hyperactivation and migration. S-Ketamine suppressed both nerve injury-induced large-conductance K Ca (BK) currents and 1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one (NS1619)-induced BK currents in spinal microglia. Furthermore, the intrathecal administration of charybdotoxin, a K Ca channel blocker, significantly inhibited the nerve injury-induced tactile allodynia, the expression of P2X 4 receptors, and the synthesis of brainderived neurotrophic factor in spinal microglia. In contrast, NS1619-induced tactile allodynia was completely inhibited by S-ketamine. These observations strongly suggest that S-ketamine preferentially suppresses the nerve injury-induced hyperactivation and migration of spinal microglia through the blockade of BK channels. Therefore, the preferential inhibition of microglial BK channels in addition to neuronal NMDA receptors may account for the preferential and potent analgesic effects of S-ketamine on neuropathic pain.

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Background and Purpose: Differentiation between hemangioblastoma and brain metastasis remains a challenge in neuroradiology using conventional MRI. Amide proton transfer (APT) imaging can provide unique molecular information. This study aimed to evaluate the usefulness of APT imaging in differentiating hemangioblastomas from brain metastases and compare APT imaging with diffusion-weighted imaging and dynamic susceptibility contrast perfusion-weighted imaging.Methods: This retrospective study included 11 patients with hemangioblastoma and 20 patients with brain metastases. Region-of-interest analyses were employed to obtain the mean, minimum, and maximum values of APT signal intensity, apparent diffusion coefficient (ADC), and relative cerebral blood volume (rCBV), and these indices were compared between hemangioblastomas and brain metastases using the unpaired t-test and Mann-Whitney U test. Their diagnostic performances were evaluated using receiver operating characteristic (ROC) analysis and area under the ROC curve (AUC). AUCs were compared using DeLong's method.Results: All MRI-derived indices were significantly higher in hemangioblastoma than in brain metastasis. ROC analysis revealed the best performance with APT-related indices (AUC = 1.000), although pairwise comparisons showed no significant difference between the mean ADC and mean rCBV.Conclusions: APT imaging is a useful and robust imaging tool for differentiating hemangioblastoma from metastasis.

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