Brain research
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Protein translation controlled through activation of mammalian target of rapamycin (mTOR) participates in many physiological and pathological processes. However, whether such activation is required for chronic pain is still unknown. Here, we examined activation of the mTOR signaling pathway during complete Freund's adjuvant (CFA)-induced chronic inflammatory pain and L5 spinal nerve ligation (SNL)-induced neuropathic pain in rats. ⋯ Interestingly, expression of neither p-mTOR nor p-S6K1 was markedly altered on days 3, 7, or 14 after L5 SNL in L5 spinal cord or DRG. These findings indicate that in DRG and spinal cord, mTOR and S6K1 are activated during chronic inflammatory pain, but not during neuropathic pain. Our results strongly suggest that mTOR and its downstream pathway contribute to the development of chronic inflammatory pain.
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Stress-induced anhedonia correlates with lower hippocampal serotonin transporter protein expression.
The serotonin transporter (5-HTT) regulates the extracellular concentration of serotonin, influencing neurotransmission. Evidence suggests that 5-HTT is altered during depression, but the precise changes in 5-HTT expression in the pathogenesis and treatment of depression are not clear. We investigated the protein expression of hippocampal 5-HTT in CD-1 mice exposed to unpredictable chronic mild stress for 10 continuous weeks. ⋯ The treatment did not alter the changes in the treatment-resistant anhedonic mice or in the non-anhedonic mice. The data indicate that down-regulation of hippocampal 5-HTT protein expression is a signature change associated with anhedonia, a key endophenotype of clinical depression. Differential changes in 5-HTT expression may contribute to variations in the susceptibility to anhedonia.
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Estrogen has multiple actions in the brain to modulate homeostasis, synaptic plasticity, neuroprotection and pain sensitivity. Previous studies have demonstrated that estradiol may affect the ion channel function. The role of voltage-gated sodium channels in the transmission of nociceptive and neuropathic pain messages is well-established. ⋯ Blockers of PKC (GÖ-6983) and PKA (H-89) abrogated these acute effects of 17β-E2. In conclusion, E2 inhibited voltage-gated Na(+) channels in mouse DRG neurons through a membrane ER-activated PKC-PKA signaling pathway. Through the modulation of voltage-gated sodium currents, estradiol could affect cell excitability, firing properties.
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Review
Optogenetic dissection of neural circuits underlying emotional valence and motivated behaviors.
The neural circuits underlying emotional valence and motivated behaviors are several synapses away from both defined sensory inputs and quantifiable motor outputs. Electrophysiology has provided us with a suitable means for observing neural activity during behavior, but methods for controlling activity for the purpose of studying motivated behaviors have been inadequate: electrical stimulation lacks cellular specificity and pharmacological manipulation lacks temporal resolution. The recent emergence of optogenetic tools provides a new means for establishing causal relationships between neural activity and behavior. ⋯ Within the amygdala, optogenetics has allowed the study of intra-amygdala microcircuitry as well as interconnections with distal regions involved in fear and anxiety. In this review, we will present the body of optogenetic studies that has significantly enhanced our understanding of emotional valence and motivated behaviors. This article is part of a Special Issue entitled Optogenetics (7th BRES).
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Accumulating evidence suggests that chemokine C-C motif receptor 2 (CCR2) plays an important role in neuropathic pain. It has been shown that spinal CCR2 is upregulated in several neuropathic pain models and expressed by neuronal and glial cells in the spinal cord. In this study, we investigated the expression changes and cellular localization of spinal CCR2 in a rat model of bone cancer induced by Walker 256 cell inoculation. ⋯ Western blot and immunohistochemical analysis demonstrated that the expression of CCR2 in the spinal cord was significantly increased on day 6, 12, and 18 in BCP rats, with a peak on day 6. Furthermore, double immunofluorescence labeling indicated that CCR2 was expressed by both microglia and neurons in the spinal cord. These results suggest that CCR2 may be involved in the development of BCP, and that targeting CCR2 may be a new strategy for the treatment of BCP.