The Journal of neuroscience : the official journal of the Society for Neuroscience
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Cannabinoids modulate the activity of many neuronal cells, among them sensory neurons in the olfactory epithelium. Here we show that the endocannabinoid 2-arachidonoyl-glycerol (2-AG) is synthesized in both olfactory receptor neurons and glia-like sustentacular cells in larval Xenopus laevis. ⋯ Hunger renders olfactory neurons more sensitive. Endocannabinoid modulation in the nose may therefore substantially influence food-seeking behavior.
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Temporomandibular disorders (TMDs) predominantly affect reproductive female patients, with pain the most frequent complaint. Although estrogens are believed to play important roles in TMD pain, the mechanism underlying modulation of TMD pain by estrogens remains largely unknown. Accumulating evidence implies that the hippocampus is involved in sexual dimorphism of pain sensitivity. ⋯ Immunostaining showed TRPV1 localized in the processes and cytoplasm of pyramidal neurons in CA1-CA3 regions of the hippocampus. Moreover, intrahippocampal injection of TRPV1 antagonists capsazepine and 5'-iodo-resiniferatoxin into the CA1 region of the hippocampus significantly attenuated allodynia of inflamed TMJ in both nonovariectomized and ovariectomized rats that received estradiol replacement. Our results suggested that hippocampal TRPV1 can modulate central pain processing and estradiol may contribute to the sexual dimorphism of TMD pain sensitivity through upregulation of TRPV1 expression in the hippocampus.
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Recent studies indicate that persistent pain after tissue or nerve injury is accompanied by an enhanced net descending facilitatory drive that contributes to an amplification and spread of pain. Although 5-HT-containing neurons in the rostral ventromedial medulla (RVM) provide the major descending serotonergic projection to the spinal cord, it is not clear whether the neurotransmitter 5-HT itself released from RVM-spinal neurons contributes to descending pain modulation. In the present study, we determined the role of the descending 5-HT in rat nocifensive behaviors after persistent pain by selectively depleting functional phenotypes of 5-HT in RVM neurons with regional shRNA interference (RNAi) of tryptophan hydroxylase-2 (Tph-2), the rate-limiting enzyme in the synthesis of neuronal 5-HT. ⋯ Furthermore, in control shRNA-treated animals, intra-RVM microinjection of brain-derived neurotrophic factor produced a reversible hyperalgesia, which was completely prevented by Tph-2 RNAi pretreatment. Descending inhibition induced by intra-RVM electrical stimulation, but not microinjection of the mu- or kappa-opioid receptor agonists in control shRNA-treated animals was eliminated in 5-HT-depleted rats. These results indicate that the descending 5-HT from the RVM is an important contributor to pain facilitation during the development of persistent pain, and may not mediate opioid-induced descending inhibition in acute pain.
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Accumulating evidence suggests that changes in neuronal chloride homeostasis may be involved in the mechanisms by which brain insults induce the development of epilepsy. A variety of brain insults, including status epilepticus (SE), lead to changes in the expression of the cation-chloride cotransporters KCC2 and NKCC1, resulting in intracellular chloride accumulation and reappearance of immature, depolarizing synaptic responses to GABA(A) receptor activation, which may critically contribute to the neuronal hyperexcitability underlying epileptogenesis. In the present study, it was evaluated whether prolonged administration of the selective NKCC1 inhibitor, bumetanide, after a pilocarpine-induced SE modifies the development of epilepsy in adult female rats. ⋯ Bumetanide did not exert any significant effects on development of spontaneous seizures nor did it enhance the effects of phenobarbital. However, combined treatment with both drugs counteracted several of the behavioral consequences of SE, which was not observed with single drug treatment. These data do not indicate that bumetanide can prevent epilepsy after SE, but the disease-modifying effect of this drug warrants further studies with more lipophilic prodrugs of bumetanide.
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Cerebellar feedforward inhibition (FFI) is mediated by two distinct pathways targeting different subcellular compartments of Purkinje cells (PCs). The axon of the granule cell, the parallel fiber, makes excitatory synapses not only onto PCs but also onto two types of interneurons, basket and stellate cells. Basket and stellate cells then send inhibitory signals to the soma and dendrites of Purkinje cells, respectively. ⋯ Unexpectedly, the parallel fiber synapse, which was considered to be facilitating during repetitive stimulation, shows depression, when the postsynaptic target is a basket cell. Other factors in the FFI circuit, such as firing properties of interneurons and dynamics of inhibitory synapses, are similar between somatic and dendritic pathways. The target-dependent parallel fiber synaptic plasticity has functional consequences for the two FFI pathways, because we observe that PCs receive transient somatic inhibition during 50 Hz stimulation of granule cells but persistent dendritic inhibition.