Plos One
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The spontaneous component of neuropathic pain (NP) has not been explored sufficiently with neuroimaging techniques, given the difficulty to coax out the brain components that sustain background ongoing pain. Here, we address for the first time the correlates of this component in an fMRI study of a group of eight patients suffering from diabetic neuropathic pain and eight healthy control subjects. Specifically, we studied the functional connectivity that is associated with spontaneous neuropathic pain with spatial independent component analysis (sICA). ⋯ In conclusion, we have characterized here for the first time a functional network of brain areas that mark the spontaneous component of NP. Pain is the result of aberrant default mode functional connectivity.
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Prostatic acid phosphatase (PAP) is expressed in nociceptive neurons and functions as an ectonucleotidase. When injected intraspinally, the secretory isoforms of human and bovine PAP protein have potent and long-lasting antinociceptive effects that are dependent on A(1)-adenosine receptor (A(1)R) activation. In this study, we purified the secretory isoform of mouse (m)PAP using the baculovirus expression system to determine if recombinant mPAP also had antinociceptive properties. ⋯ Our studies indicate that PAP has species-conserved antinociceptive effects and has pH-dependent ectonucleotidase activity. The ability to metabolize nucleotides in a pH-dependent manner could be relevant to conditions like inflammation where tissue acidosis and nucleotide release occur. Lastly, our studies demonstrate that recombinant PAP protein can be used to treat chronic pain in animal models.
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A stimulus approaching the body requires fast processing and appropriate motor reactions. In monkeys, fronto-parietal networks are involved both in integrating multisensory information within a limited space surrounding the body (i.e. peripersonal space, PPS) and in action planning and execution, suggesting an overlap between sensory representations of space and motor representations of action. In the present study we investigate whether these overlapping representations also exist in the human brain. ⋯ This pattern of corticospinal modulation highlights the relation between space and time in the pps representation: an early facilitation for near stimuli may reflect immediate motor preparation, whereas, at later time intervals, motor preparation relates to distant stimuli potentially approaching the body.
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Adipose tissue is a critical mediator in obesity-induced insulin resistance. Previously we have demonstrated that pharmacological lowering of glycosphingolipids and subsequently GM3 by using the iminosugar AMP-DNM, strikingly improves glycemic control. Here we studied the effects of AMP-DNM on adipose tissue function and inflammation in detail to provide an explanation for the observed improved glucose homeostasis. ⋯ In addition, we found that adiponectin gene expression and protein were increased by AMP-DNM. As a consequence of this improved function of fat tissue we observed less inflammation, which was characterized by reduced numbers of adipose tissue macrophages (crown-like structures) and reduced levels of the macrophage chemo attractants monocyte-chemoattractant protein-1 (Mcp-1/Ccl2) and osteopontin (OPN). In conclusion, pharmacological lowering of glycosphingolipids by inhibition of glucosylceramide biosynthesis improves adipocyte function and as a consequence reduces inflammation in adipose tissue of obese animals.
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Emerging research implicates the participation of spinal dorsal horn (SDH) neurons and astrocytes in nerve injury-induced neuropathic pain. However, the crosstalk between spinal astrocytes and neurons in neuropathic pain is not clear. Using a lumbar 5 (L5) spinal nerve ligation (SNL) pain model, we testified our hypothesis that SDH neurons and astrocytes reciprocally regulate each other to maintain the persistent neuropathic pain states. ⋯ Meanwhile, L-AA shortened the duration of neuronal activation by SNL. Our data offers evidence that neuronal and astrocytic activations are closely related with the maintenance of neuropathic pain through a reciprocal "crosstalk". The current study suggests that neuronal and non-neuronal elements should be taken integrally into consideration for nociceptive transmission, and that the intervention of such interaction may offer some novel pain therapeutic strategies.