C.M., who is also a recipient of grant R01 DA012609 from the National Institutes of Health. Abbreviations ACEA arachidonyl-2-chloroethylamide aCSF artificial cerebrospinal fluid AM251 (N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) AM281 (1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide) CGP-55845 ((2S)-3-[[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2-hydroxypropyl](phenylmethyl)

Akt inhibitor phosphinic acid) CGRP calcitonin gene-related peptide CI confidence interval CTAP D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 DMSO dimethyl sulfoxide DRG dorsal root ganglion GPCR G protein-coupled receptor NK1R neurokinin 1 receptor TRPV1 transient receptor potential cation channel, subfamily V, member 1 “
“Glutamate is the major excitatory neurotransmitter in the central nervous system. Considerable evidence suggests that both ionotropic and metabotropic glutamate receptors are involved in pain hypersensitivity. However, glutamate receptor-based therapies are limited by side-effects because the activities of glutamate receptors are essential for many important physiological functions. Here, we review recent key findings in molecular and cellular mechanisms of glutamate receptor regulation and their roles in triggering

and sustaining pain hypersensitivity. Targeting these molecular mechanisms could form the basis for new therapeutic strategies for the treatment of chronic pain. “
“Stress exposure resulted in brain induction

of immediate-early selleck compound genes (IEGs), considered as markers of neuronal activation. Upon repeated exposure to the same stressor, reduction of IEG response (adaptation) has been often observed, but there are important discrepancies in literature that may be in part related to the particular IEG and methodology used. We studied the differential pattern of adaptation of the IEGs c-fos and arc (activity-regulated cytoskeleton-associated protein) after repeated exposure to a severe stressor: immobilization on wooden boards (IMO). Rats repeatedly exposed to IMO showed reduced c-fos mRNA levels in response to acute BCKDHB IMO in most brain areas studied: the medial prefrontal cortex (mPFC), lateral septum (LS), medial amygdala (MeA), paraventricular nucleus of the hypothalamus (PVN) and locus coeruleus. In contrast, the number of neurons showing Fos-like immunoreactivity was only reduced in the MeA and the various subregions of the PVN. IMO-induced increases in arc gene expression were restricted to telencephalic regions and reduced by repeated IMO only in the mPFC. Double-labelling in the LS of IMO-exposed rats revealed that arc was expressed in only one-third of Fos+ neurons, suggesting two populations of Fos+ neurons. These data suggest that c-fos mRNA levels are more affected by repeated IMO than corresponding protein, and that arc gene expression does not reflect adaptation in most brain regions, which may be related to its constitutive expression.