Brain research bulletin
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Neuroimaging studies suggest that spinal cord injury (SCI) may lead to significant anatomical alterations in the human sensorimotor system. In particular, voxel-based morphometry (VBM) of cortical volume has revealed a significant gray and white matter atrophy bilaterally in the primary sensory cortex (S1). By contrast, some structural studies failed to detect changes in gray matter volume (GMV) in the primary motor cortex (M1) following SCI, whereas others have reported a substantial decrease of GMV also in M1. ⋯ The wide range of disease duration, rehabilitation training, drug intervention, and different research methodology, especially the identification of region of interest and the statistical approach to correct for multiple comparisons, may have contributed to some inconsistencies between the reviewed studies. Nevertheless, neuroimaging biomarkers can assess the extent of neural damage, elucidate the mechanisms of neural repair, and predict clinical outcome. A better understanding of the structural and functional changes that occur at cortical level following SCI may be useful in tracking potential treatment induced changes and identifying potential therapeutic targets, thus developing evidence-based rehabilitation therapies.
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Brain research bulletin · Oct 2017
A novel method for oxygen glucose deprivation model in organotypic spinal cord slices.
This study aimed to establish a model to closely mimic spinal cord hypoxic-ischemic injury with high production and high reproducibility. Fourteen-day cultured organotypic spinal cord slices were divided into 4 groups: control (Ctrl), oxygen glucose deprived for 30min (OGD 30min), OGD 60min, and OGD 120min. The Ctrl slices were incubated with 1ml propidium iodide (PI) solution (5μg/ml) for 30min. ⋯ The increase was significant between 30min and 60min, but not significant between 60min and 120min. Organotypic spinal cord slices cultured in glucose-free medium and anaerobic incubator could mimic hypoxia-ischemia of the spinal cord perfectly; 60min could be the best duration for OGD. This technique might be a simple and efficient method to obtain in vitro model for spinal cord hypoxic-ischemic injury in sufficient number and with high quality.
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Brain research bulletin · Oct 2017
Chemokine CCL8 and its receptor CCR5 in the spinal cord are involved in visceral pain induced by experimental colitis in mice.
Visceral hypersensitivity induced by inflammatory bowel disease (IBD) is a clinical challenge since the underlying mechanisms remain elusive. Chemokines and their receptors have been suggested to modulate inflammatory pain and neuropathic pain. However, the exact chemokines involved in visceral pain remain to be determined. ⋯ Finally, intrathecal CCL8 neutralizing antibody or CCR5 antagonist DAPTA dose-dependently suppressed TNBS-evoked visceral hyperalgesia and spinal ERK activation. Taken together, these data demonstrated that CCL8 and CCR5, expressed and upregulated in spinal neurons after colonic inflammation, are involved in the maintenance of visceral hyperalgesia via the activation of spinal ERK. Targeting CCL8/CCR5/ERK pathway in the spinal cord might provide a novel treatment for the relief of visceral pain.
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Brain research bulletin · Oct 2017
Downregulations of TRPM8 expression and membrane trafficking in dorsal root ganglion mediate the attenuation of cold hyperalgesia in CCI rats induced by GFRα3 knockdown.
Cold hyperalgesia is an intractable sensory abnormality commonly seen in peripheral neuropathies. Although glial cell line-derived neurotrophic factor family receptor alpha3 (GFRα3) is required for the formation of pathological cold pain has been revealed, potential transduction mechanism is poorly elucidated. We have previously demonstrated the contribution of enhanced activity of transient receptor potential melastatin 8 (TRPM8) to cold hyperalgesia in neuropathic pain using a rat model of chronic constriction injury (CCI) to the sciatic nerve. Recently, the enhancement of TRPM8 activity is attributed to the increased TRPM8 plasma membrane trafficking. In addition, TRPM8 can be sensitized by the activation of GFRα3, leading to increased cold responses in vivo. The aim of this study was to investigate whether GFRα3 could influence cold hyperalgesia of CCI rats via modulating TRPM8 expression and plasma membrane trafficking in dorsal root ganglion (DRG). ⋯ Our results demonstrate that GFRα3 knockdown specially inhibits cold hyperalgesia following CCI via decreasing the expression level and plasma membrane trafficking of TRPM8 in DRG. GFRα3 and its downstream mediator, TRPM8, represent a new analgesia axis which can be further exploited in sensitized cold reflex under the condition of chronic pain.
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Brain research bulletin · Sep 2017
Influence of social interaction on nociceptive-induced changes in locomotor activity in a mouse model of acute inflammatory pain: Use of novel thermal assays.
Most acute and chronic animal models of pain rely heavily on reflexive assays for evaluating levels of nociception, which involves removing the animal from its normal social environment. Here, we examine and characterize the influence of social interactions on inflammatory pain-evoked changes in movement in two different mouse strains. To produce inflammatory nociception, we injected CFA bilaterally into the hind paws of Balb/c and C3H mice and then recorded exploratory locomotor activity using an automated detector system to first evaluate the effects of social behavior on nociception. ⋯ Carprofen administration completely blocked this CFA-induced hyperlocomotor activity. Both heat and cold induced a significant increase in locomotor activity in paired mice injected with CFA, while having no effect on activity in control mice injected with saline. The results presented here indicate that social interactions greatly influence inflammatory pain-induced changes in locomotor activity and indicate that the use of movement-based assays to evaluate nociception in paired mice may provide an alternative and more sensitive method to quantify nociception and characterize novel analgesic effects over time in the context of social interactions in rodent models of pain.