Pain
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Pain-related adaptations in movement require a network architecture that allows for integration across pain and motor circuits. Previous studies addressing this issue have focused on cortical areas such as the midcingulate cortex. Here, we focus on pain and motor processing in the human cerebellum. ⋯ Activation in these multimodal regions persisted when pain and motor processes were combined within the same trial, and activation in contralateral left lobule VIIb persisted when stimulation was controlled for. Functional connectivity analyses revealed significant correlations in the BOLD time series between multimodal cerebellar regions and sensorimotor regions in the cerebrum including anterior midcingulate cortex, supplementary motor area, and thalamus. The current findings are the first to show multimodal processing in lobules VI and VIIb for motor control and pain processing and suggest that the posterior cerebellum may be important in understanding pain-related adaptations in motor control.
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Obesity is associated with several pain disorders including headache. The effects of obesity on the trigeminal nociceptive system, which mediates headache, remain unknown. We used 2 complementary mouse models of obesity (high-fat diet and leptin deficiency) to examine this. ⋯ We observed higher calcium influx in cultured trigeminal ganglia neurons from obese mice and a higher percentage of medium to large diameter capsaicin-responsive cells. These findings demonstrate that obesity results in functional changes in the trigeminal system that may contribute to abnormal sensory processing. Our findings provide the foundation for in-depth studies to improve the understanding of the effects of obesity on the trigeminal system and may have implications for the pathophysiology of headache disorders.
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Recent studies reported the translocator protein (TSPO) to play critical roles in several kinds of neurological diseases including the inflammatory and neuropathic pain. However, the precise mechanism remains unclear. This study was undertaken to explore the distribution and possible mechanism of spinal TSPO against chronic neuropathic pain (CNP) in a rat model of L5 spinal nerve ligation (SNL). ⋯ Ro5-4864 also attenuated the spinal CXCR2 and p-ERK expressions. These results suggested that early upregulation of TSPO could elicit potent analgesic effects against CNP, which might be partly attributed to the inhibition of CXCL1-CXCR2-dependent astrocyte-to-neuron signaling and central sensitization. TSPO signaling pathway may present a novel strategy for the treatment of CNP.
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The contribution of the peripheral nervous system to opiate-induced hyperalgesia (OIH) is not well understood. In this study, we determined the changes in excitability of primary sensory neurons after sustained morphine administration for 7 days. Changes in the expression of glutamate receptors and glutamate transporters after morphine administration were ascertained in dorsal root ganglions. ⋯ Coadministration in vivo of the GluN2B selective antagonist Ro 25-6981 with morphine for 7 days prevented the appearance of OIH and increased morphine-induced analgesia. Administration of morphine for 7 days led to an increased expression of GluN2B and excitatory amino acid transporter 3/excitatory amino acid carrier 1, but not of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate, kainate, or group I metabotropic glutamate receptors, or of the vesicular glutamate transporter 2. These results suggest that peripheral glutamatergic neurotransmission contributes to OIH and that GluN2B subunit of NMDA receptors in the periphery may be a target for therapy.