Brain research
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The pathogenesis of neuropathic pain remains largely unknown. Epigenetic mechanisms may play a major role in regulating expression of pro- or antinociceptive genes. DNA methylation is a major epigenetic mechanism in vertebrates, and methyl- CpG-binding protein 2 (MeCP2) is directly involved in methylation-mediated gene silencing. ⋯ Mechanical allodynia and thermal hyperalgesia induced by CCI were attenuated by intrathecal 5-azacytidine from day 5 to day 14 after CCI surgery. The increases in global DNA methylation and MeCP2 expression in the spinal cord in CCI rats were also significantly inhibited by intrathecal 5-azacytidine. These results demonstrate that increased global DNA methylation and MeCP2 expression in the spinal cord after nerve damage may play an important role in neuropathic pain. 5-azacytidine shows potential for treating neuropathic pain.
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Autism has been hypothesized to reflect neuronal disconnection. Several recent reports implicate the key thalamic relay nuclei and cortico-thalamic connectivity in the pathophysiology of autism. Accordingly, we aimed to focus on evaluating the integrity of the thalamic radiation and sought to replicate prior white matter findings in Korean boys with high-functioning autism spectrum disorders (ASD) using Diffusion Tensor Imaging (DTI). ⋯ Our preliminary findings support evidence implicating disturbances in the thalamo-frontal connections in autism. These findings highlight the role of hypoconnectivity between the frontal cortex and thalamus in ASD.
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The tactile sense comprises pathways for both discriminative and affective touch. Low threshold unmyelinated mechanoafferents (C tactile, CT) in the human hairy skin have recently been linked to pleasant touch sensation. Here, we investigated how perception of the hedonic aspect of tactile stimulation differs between the hairy skin of the arm, and the glabrous skin of the palm, which is not innervated by CT afferents. ⋯ We found that the order of stimulus presentation, palm/arm or arm/palm, has an effect on pleasantness ratings of gentle brush stroking with varying velocity. Notably, the perception of pleasantness for palm stimulation was affected by previous stimulation of the arm, but not vice versa. Thus, assessment of valence of touch may be influenced by affective reactions elicited by activation of the CT afferent pathway.
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Many phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive (IR) cells are expressed in the trigeminal spinal subnucleus caudalis (Vc), upper cervical spinal cord (C1-C2), nucleus tractus solitarii (NTS) and paratrigeminal nucleus (Pa5) after capsaicin injection into the whisker pad (WP), masseter muscle (MM), digastric muscle (DM) or sternohyoideus muscle (SM). The pERK-IR cells also showed NeuN immunoreactivity, indicating that ERK phosphorylation occurs in neurons. The pERK-IR cells were significantly reduced after intrathecal injection of MEK 1/2 inhibitor PD98059. ⋯ In the ipsilateral Pa5, many pERK-IR cells were observed following capsaicin injection into the SM. The number of swallows elicited by distilled water administration was significantly smaller after capsaicin injection into the WP, MM or DM but not SM compared to that of vehicle-injected rats. Various noxious inputs due to the masticatory or swallowing-related muscle inflammation may be differentially involved in muscle pain and swallowing reflex activity.
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Adaptation has a pronounced impact on the perception of vibrotactile stimuli. Previously, we demonstrated that the duration of vibrotactile conditioning was directly proportional to the impact that adaptation has on sensory perception (Tannan et al., 2007b). Prior reports had proposed that the impact of adaptation on the perceived magnitude of vibrotactile stimuli was specific to the conditioning amplitude (Goble and Hollins, 1993), and this concept led us to hypothesize that if the amplitude of a vibrotactile stimulus was changed continuously, that this modulation would itself impact adaptation. ⋯ Changing the standard amplitude yielded results consistent with Weber's Law and changing the modulation rate yielded results that were consistent with our initial hypothesis that faster modulation rates would lead to the non-stationary stimulus as being less adapted. A comparative study, using the above-described method, was conducted with 12 autism subjects who were previously reported to have below normal adaptation metrics (Tannan et al., 2008). The findings of this pilot autism study suggest that rate dependent modulation of vibrotactile stimuli could provide a more sensitive metric of adaptation, as the observations demonstrate a bimodal distribution within the autism spectrum.