Experimental neurology
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Experimental neurology · Sep 2003
Clinical Trial Controlled Clinical TrialSubstance-P-induced protein extravasation is bilaterally increased in complex regional pain syndrome.
Pain, mechanical hyperalgesia, edema, increased skin temperature, and skin reddening are characteristic symptoms of acute complex regional pain syndrome (CRPS). We have recently demonstrated facilitated neurogenic inflammation on the affected limb. To further elucidate the underlying mechanisms, exogenous substance P (SP) in ascending concentrations (10(-9), 10(-8), 10(-7), 10(-6) M) was intradermally applied to the affected and the unaffected limbs, respectively, in two groups of 11 CRPS patients each using the microdialysis technique. ⋯ We conclude that SP-induced plasma protein extravasation is increased in CRPS patients on both the affected and unaffected limbs. The underlying mechanism might be impaired SP inactivation. Thus, our results further support the hypothesis that neurogenic inflammation plays an important role in the initiation of CRPS.
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Experimental neurology · Sep 2003
Autonomic dysreflexia after spinal cord transection or compression in 129Sv, C57BL, and Wallerian degeneration slow mutant mice.
To study plasticity of central autonomic circuits that develops after spinal cord injury (SCI), we have characterized a mouse model of autonomic dysreflexia. Autonomic dysreflexia is a condition in which episodic hypertension occurs after injuries above the midthoracic segments of the spinal cord. As synaptic plasticity may be triggered by axonal degeneration, we investigated whether autonomic dysreflexia is reduced in mice when axonal degeneration is delayed after SCI. ⋯ To determine if differences in afferent arbor sprouting could explain our observations, we assessed changes in the afferent arbor in each mouse strain after both SCT and CCI. We show that independent of the type of injury, 129Sv mice but not C57BL or Wld(S) mice demonstrated an increased small-diameter CGRP-immunoreactive afferent arbor after SCI. Our work thus suggests a role for Wallerian degeneration in the development of autonomic dysreflexia and demonstrates that the choice of mouse strain and injury model has important consequences to the generalizations that may be drawn from studies of SCI in mice.
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Experimental neurology · Sep 2003
Increased expression and localization of the RNA-binding protein HuD and GAP-43 mRNA to cytoplasmic granules in DRG neurons during nerve regeneration.
The neuronal-specific RNA-binding protein, HuD, binds to a U-rich regulatory element of the 3' untranslated region (3' UTR) of the GAP-43 mRNA and delays the onset of its degradation. We have recently shown that overexpression of HuD in embryonic rat cortical cells accelerated the time course of normal neurite outgrowth and resulted in a twofold increase in GAP-43 mRNA levels. Given this evidence, we sought to investigate the involvement of HuD during nerve regeneration. ⋯ Not only were the temporal patterns of expression of HuD protein and GAP-43 mRNA similar, but also they were found to colocalize in the cytoplasm of DRG neurons. Moreover, both molecules were distributed in cytoplasmic granules containing ribosomal RNA. In conclusion, our results suggest that HuD is involved in the upregulation of GAP-43 expression observed at early stages of peripheral nerve regeneration.
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Experimental neurology · Sep 2003
Inhibitory effect of intrathecal glycine on the micturition reflex in normal and spinal cord injury rats.
We examined the influence of lumbosacral glycinergic neurons on the spinobulbospinal and spinal micturition reflexes. Female rats were divided into intact rats, rats with acute injury to the lower thoracic spinal cord (SCI), and rats with chronic SCI. Under urethane anesthesia, isovolumetric cystometry was performed in each group before and after intrathecal (IT) injection of glycine or strychnine into the lumbosacral cord level. ⋯ On amino acid analysis, IT glycine (0.01-100 microg) decreased the glutamate level of the lumbosacral cord in intact rats, but not in chronic SCI rats. The glycine level of the lumbosacral cord was 54% lower in chronic SCI rats when compared with intact rats, while the GlyR alpha1 mRNA level did not change after SCI. These results suggest that glycinergic neurons may have an important inhibitory effect on the spinobulbospinal and spinal micturition reflexes at the level of the lumbosacral cord.
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Experimental neurology · Aug 2003
Gabapentin reverses mechanical allodynia induced by sciatic nerve ischemia and formalin-induced nociception in mice.
The anticonvulsant drug gabapentin has been demonstrated to alleviate symptoms of painful diabetic neuropathy as well as other types of neuropathic pain. The aim of the present study was to investigate the effect of gabapentin in a recently developed mouse model of peripheral neuropathy. This model is based on a photochemical ischemic lesion of the sciatic nerve generated by laser-induced activation of the photosensitizing dye erythrosin B. ⋯ Gabapentin did not affect the tactile withdrawal threshold in intact animals. A dose of gabapentin (100 micromol/kg, sc) that had no effect on allodynia was found to significantly reduce the pain behavior during phase 2 of the formalin test. The present study demonstrates that systemic administration of gabapentin suppresses both allodynia induced by an ischemic lesion of the sciatic nerve and pain behavior in the formalin test.