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Downregulation of the potassium chloride cotransporter type 2 (KCC2) after a spinal cord injury (SCI) disinhibits motoneurons and dorsal horn interneurons causing spasticity and neuropathic pain, respectively. We showed recently (Bos et al., 2013) that specific activation of 5-HT 2A receptors by TCB-2 [(4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine hydrobromide] upregulates KCC2 function, restores motoneuronal inhibition and reduces SCI-induced spasticity. Here, we tested the potential analgesic effect of TCB-2 on central (thoracic hemisection) and peripheral [spared nerve injury (SNI)] neuropathic pain. We found mechanical and thermal hyperalgesia reduced by an acute administration of TCB-2 in rats with SCI. This analgesic effect was associated with an increase in dorsal horn membrane KCC2 expression and was prevented by pharmacological blockade of KCC2 with an intrathecal injection of DIOA [(dihydroindenyl)oxy]alkanoic acid]. In contrast, the SNI-induced neuropathic pain was not attenuated by TCB-2 although there was a slight increase of membrane KCC2 expression in the dorsal horn ipsilateral to the lesion. Up-regulation of KCC2 function by targeting 5-HT 2A receptors, therefore, has therapeutic potential in the treatment of neuropathic pain induced by SCI but not by SNI., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

Spectra of "white LEDs" are characterized by an intense emission in the blue region of the visible spectrum, absent in daylight spectra. This blue component and the high intensity of emission are the main sources of concern about the health risks of LEDs with respect to their toxicity to the eye and the retina. The aim of our study was to elucidate the role of blue light from LEDs in retinal damage. Commercially available white LEDs and four different blue LEDs (507, 473, 467, and 449nm) were used for exposure experiments on Wistar rats. Immunohistochemical stain, transmission electron microscopy, and Western blot were used to exam the retinas. We evaluated LED-induced retinal cell damage by studying oxidative stress, stress response pathways, and the identification of cell death pathways. LED light caused a state of suffering of the retina with oxidative damage and retinal injury. We observed a loss of photoreceptors and the activation of caspase-independent apoptosis, necroptosis, and necrosis. A wavelength dependence of the effects was observed. Phototoxicity of LEDs on the retina is characterized by a strong damage of photoreceptors and by the induction of necrosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The affinities of several 5-hydroxy-indole derivatives for serotonin-1 (5-HT1) binding site subtypes, labeled with 2 nM [3H]5-HT, were assessed by quantitative autoradiography on rat brain sections. The results obtained with known ligands, namely 5-hydroxytryptamine (5-HT), 5-methoxytryptamine (5-Me-OT), 5-methoxy-N,N- dimethyl-tryptamine (5-Me-ODMT), 5-hydroxy-N,N-dimethyl-tryptamine (bufotenine) and 8-hydroxy-2-[di-N-propylamino]tetralin (8-OH-DPAT) demonstrate the reliability and the advantages of this technique for pharmacological studies. Novel serotonin derivatives were synthesized by carboxymethylation of the hydroxyl group. One of those new ligands, serotonin-O-carboxy-methyl- glycyl-tyrosinamide (S-CM-GTNH2), inhibited 2 nM [3H]5-HT binding to the substantia nigra with an IC50 of 22.4 nM, a value which is 22 times lower than that found in the dentate gyrus and choroid plexus. This demonstrates the preferential affinity of S-CM-GTNH2 for 5-HT1B versus 5-HT1A and 5-HT1C binding sites. S-CM-GTNH2 contains a tyrosine residue, which may be useful for the synthesis of a radioactive iodinated molecule and for the preparation of 'long-lasting ligands' linked through peptide bonds with a protein. These derivatives could be of great interest for ultrastructural and behavioral studies relevant to 5-HT1B sites.