Neuroscience
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Surgical trauma can affect spinal neuronal excitability, but there have been no studies of the effects of surgical cutaneous injury on central nociceptive processing of deep afferent inputs evoked by noxious stimuli such as capsaicin. Thus our aim was to test the effect of surgical cutaneous incision in influencing central sensitization induced by capsaicin injection into the temporomandibular joint (TMJ). The activity of single nociceptive neurons activated by noxious mechanical stimulation of the TMJ was recorded in the trigeminal subnucleus caudalis/upper cervical cord of halothane-anesthetized rats. ⋯ Incision itself induced a barrage of neuronal spikes and excitability increases reflecting central sensitization (cutaneous RF expansion, cutaneous MAT reduction) in most neurons tested whereas lidocaine pretreatment significantly attenuated the barrage and central sensitization. Capsaicin injection into the TMJ induced cutaneous RF expansion, cutaneous MAT reduction and TMJ MAT reduction following lidocaine pretreatment of the cutaneous incision site whereas capsaicin injection following incision alone not only failed to induce further central sensitization but also decreased the existing incision-induced central sensitization (no cutaneous RF expansion, increased cutaneous MAT and TMJ MAT) in most neurons tested. These findings suggest that central sensitization induced by capsaicin alone or by cutaneous incision alone can readily occur in TMJ-responsive nociceptive neurons and that following incision-induced excitability increases, capsaicin may result in a temporary suppression of nociceptive neuronal changes reflecting central sensitization.
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Drug addiction is a state of altered brain reward and self-regulation mediated by both neurotransmitter and hormonal systems. Although an organism's internal system attempts to maintain homeostasis when challenged by exogenous opiates and other drugs of abuse, it eventually fails, resulting in the transition from drug use to drug abuse. We propose that the attempted maintenance of hormonal homeostasis is achieved, in part, through alterations in levels of processing enzymes that control the ratio of active hormone to pro-hormone. ⋯ Promoter activity experiments in rat somatomammotrope GH3 cells containing the mu-opioid receptor demonstrated that the CRE(s) in the promoter of PC1/3 and PC2 is required for morphine-induced regulation of PC1/3 and PC2. Our data suggest that the regulation of the prohormone processing system by morphine may lead to alterations in the levels of multiple bioactive hormones and may be a compensatory mechanism whereby the organism tries to restore its homeostatic hormonal milieu. The down-regulation of PC1/3, PC2 and P-CREB by short-term morphine and up-regulation by long-term morphine treatment may be a signal mediating the switch from drug use to drug abuse.
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In the present study, we characterized differential expressions of phosphorylated Ca(2+)/calmodulin-dependent protein kinase IIalpha (pCaMKIIalpha) and phosphorylated extracellular signal-regulated protein (pERK) in the mouse hippocampus induced by various nociceptive stimuli. In an immunoblot study, s.c. injection of formalin and intrathecal (i.t.) injections of glutamate, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1 beta) significantly increased pCaMKIIalpha expression in the hippocampus, but i.p. injections of acetic acid did not. pERK1/2 expression was also increased by i.t. injection of glutamate, TNF-alpha, and IL-1beta but not by s.c. injections of formalin or i.p. injections of acetic acid. ⋯ PD98059 as well as KN-93 significantly attenuated the nociceptive behavior induced by glutamate, pro-inflammatory cytokines, and acetic acid. Our results suggest that (1) pERKalpha and pCaMK-II located in the hippocampus are important regulators during the nociceptive processes induced by s.c. formalin, i.t. glutamate, i.t. pro-inflammatory cytokines, and i.p. acetic acid injection, respectively, and (2) the alteration of pERK and pCaMKIIalpha in nociceptive processing induced by formalin, glutamate, pro-inflammatory cytokines and acetic acid was modulated in a different manner.
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The use of deep brain stimulation (DBS) as an effective clinical therapy for a number of neurological disorders has been greatly hindered by the lack of understanding of the mechanisms which underlie the observed clinical improvement in patients. This problem is confounded by the difficulty of investigating the neuronal effects of DBS in situ, and the impossibility of measuring the induced current in vivo. In our recent computational work using a quasi-static finite element (FEM) model we have quantitatively shown that the properties of the depth electrode-brain interface (EBI) have a significant effect on the electric field induced in the brain volume surrounding the DBS electrode. ⋯ Results showed that the EBI affected the waveform shaping differently at different post-implantation stages, and that this in turn had implications on induced current distribution across the EBI. Furthermore, we investigated whether hypothetical waveforms, which were shown to have potential usefulness for neural stimulation but are not yet applied clinically, would have any advantage over the currently used square pulse. In conclusion, the influence of reactivity of the EBI on the crossing stimulation current in therapeutic DBS is significant, and affects the predictive estimation of current distribution around the implanted DBS electrode in the human brain.
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Oscillatory activity is a prominent characteristic of electrophysiological recordings in the olfactory system and has been proposed to play a key role in encoding olfactory representations. Studies in several systems have shown that some aspects of information coding involve characteristics that intertwine spikes and fast oscillations (in the beta and gamma range) of local field potentials (LFP). In the insect olfactory system, it has been proposed that oscillatory activity could provide a temporal link between cells. ⋯ Our results suggest that gamma oscillation may act as a temporal filter. Oscillatory phase-coupled spikes in the OB could act in increasing the probability of spike emission in the aPC cell during a narrow time-window, explaining the tight phase-coupling observed in the aPC. The role of spike-LFP phase-coupling as a binding function between odor features is discussed.