Experimental neurology
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Experimental neurology · Apr 2007
Effects of decompression on neuropathic pain behaviors and skin reinnervation in chronic constriction injury.
Decompression is an important therapeutic strategy to relieve neuropathic pain clinically; there is, however, lack of animal models to study its temporal course of neuropathic pain behaviors and its influence on nerve regeneration to sensory targets. To address these issues, we established a model of decompression on rats with chronic constriction injury (CCI) and investigated the effect on skin reinnervation. Animals were divided into a decompression group, in which the ligatures were removed, and a CCI group, in which the ligatures remained at postoperative week 4 (POW 4). ⋯ At POW 8, neuropathic pain behaviors had completely disappeared in the decompression group, and the decompression group had a higher skin innervation index of SP than the CCI group (0.45+/-0.05 vs. 0.16+/-0.03, p<0.001). These indexes were similar in both groups for PGP 9.5 (0.32+/-0.09 vs. 0.14+/-0.04, p=0.11) and CGRP (0.38+/-0.06 vs. 0.21+/-0.07, p=0.09). These findings demonstrate the temporal changes in the disappearance of neuropathic pain behaviors after decompression and suggest that decompression causes different patterns of skin reinnervation for different markers of skin innervation.
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Experimental neurology · Mar 2007
p38 activation in uninjured primary afferent neurons and in spinal microglia contributes to the development of neuropathic pain induced by selective motor fiber injury.
Compelling evidence shows that the adjacent uninjured primary afferents play an important role in the development of neuropathic pain after nerve injury. The underlying mechanisms, however, are largely unknown. In the present study, the selective motor fiber injury was performed by L5 ventral root transection (L5 VRT), and p38 activation in dorsal root ganglia (DRG) and L5 spinal dorsal horn was examined. ⋯ Intrathecal injection of p38 inhibitor SB203580, starting before L5 VRT, inhibited the abnormal pain behaviors. Post-treatment with SB203580 performed at the 1st day or at the 8th day after surgery also reduced established neuropathic pain. These data suggest that p38 activation in uninjured DRGs neurons and in spinal microglia is necessary for the initiation and maintenance of neuropathic pain induced by L5 VRT.
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Experimental neurology · Mar 2007
At-level neuropathic pain is induced by lumbosacral ventral root avulsion injury and ameliorated by root reimplantation into the spinal cord.
Neuropathic pain is common after traumatic injuries to the cauda equina/conus medullaris and brachial plexus. Clinically, this pain is difficult to treat and its mechanisms are not well understood. Lesions to the ventral roots are common in these injuries, but are rarely considered as potential contributors to pain. ⋯ Quantitative immunohistochemistry showed increased levels of inflammatory markers in laminae III-V and in the dorsal funiculus of the L5 spinal cord of VRA, but not VRA+Imp rats, specific to areas that receive projections from mechanoreceptive, but not nociceptive, primary afferents. These data suggest that sustained at-level neuropathic pain can develop following a pure motor lesion, whereas the pain may be ameliorated by acute root reimplantation. We believe that our findings are of translational research interest, as root implantation surgery is emerging as a potentially useful strategy for the repair of cauda equina/conus medullaris injuries.
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Experimental neurology · Mar 2007
Neurobehavioral functional deficits following closed head injury in the neonatal pig.
Neurobehavioral deficits in higher cortical systems have not been described previously in a large animal model of diffuse brain injury. Anesthetized 3-5 day old piglets were subjected to either mild (142 rad/s) or moderate (188 rad/s) rapid non-impact axial rotations of the head. Multiple domains of cortical function were evaluated 5 times during the 12 day post-injury period using tests of neurobehavioral function devised for piglets. ⋯ Neurobehavioral functional deficits correlated with neuropathologic damage in the neonatal pigs after inertial head injury. Injured axons detected by immunohistochemistry (beta-APP) were absent in mild injury and sham piglets, but were observed in moderately injured piglet brains. In summary, we have developed a quantitative battery of neurobehavioral functional assessments for large animals that correlate with neuropathologic axonal damage and may have wide applications in the fields of cardiac resuscitation, stroke, and hypoxic-ischemic brain injury.
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Experimental neurology · Mar 2007
Comparative StudyHypothermia in acute stroke--slow versus fast rewarming an experimental study in rats.
The rewarming phase after therapeutic hypothermia in cerebral ischemia appears crucial as rapid rewarming may lead to rebound phenomena and enhance deleterious ischemic effects. We hypothesized that slow and controlled rewarming after moderate hypothermia is superior to fast rewarming in rats subjected to 90 min temporary middle cerebral artery occlusion (tMCAO). Two experiments were designed: (i) 34 rats were randomly assigned to either normothermic treatment, to hypothermia (33 degrees C) with rapid rewarming within 20 min, or to hypothermia with slow rewarming within 2 h after 4 h of hypothermia starting 2 h after tMCAO. ⋯ Glutamate release was significantly higher at 4 distinct time points in the control group. Slow rewarming after a period of hypothermia is superior to fast rewarming. It may blunt deleterious rebound effects such as overexpression of AQP4, sustain anti-inflammatory mechanisms and thereby preserve the neuroprotection delivered by hypothermia.