Experimental neurology
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Experimental neurology · Jul 2010
Task-specificity vs. ceiling effect: step-training in shallow water after spinal cord injury.
While activity-based rehabilitation is one of the most promising therapeutic approaches for spinal cord injury, the necessary components for optimal locomotor retraining have not yet been determined. Currently, a number of different activity-based approaches are being investigated including body weight-supported treadmill training (with and without manual assistance), robotically-assisted treadmill training, bicycling and swimming, among others. We recently showed, in the adult rat, that intensive rehabilitation based on swimming brought about significant improvements in hindlimb performance during swimming but did not alter the normal course of recovery of over-ground walking (Smith et al., 2006a,b, 2009). ⋯ These observations support previous suggestions that incompletely injured animals retrain themselves while moving about in their cages and that daily training regimes are not able to improve upon this already substantial functional improvement due to a ceiling effect, rather than task-specificity, per se. These results also support the concept that moderately-severe thoracic contusion injuries decrease the capacity for body weight support, but do not decrease the capacity for pattern generation. In contrast, animals with severe contusion injuries could not support their body weight nor could they generate a locomotor pattern when provided with body weight support via buoyancy.
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Experimental neurology · Jul 2010
The COX-2 inhibitor parecoxib is neuroprotective but not antiepileptogenic in the pilocarpine model of temporal lobe epilepsy.
The enzyme cyclooxygenase-2 (COX-2), which catalyzes the production of pro-inflammatory prostaglandins, is induced in the brain after various insults, thus contributing to brain inflammatory processes involved in the long-term consequences of such insults. Mounting evidence supports that inflammation may contribute to epileptogenesis and neuronal injury developing after brain insults. Anti-inflammatory treatments, such as selective COX-2 inhibitors, may thus constitute a novel approach for anti-epileptogenesis or disease-modification after brain injuries such as head trauma, cerebral ischemia or status epilepticus (SE). ⋯ However, the incidence, frequency or duration of spontaneous seizures developing after SE or the behavioral and cognitive alterations associated with epilepsy were not affected by parecoxib. Only the severity of spontaneous seizures was reduced, indicating a disease-modifying effect. These results substantiate that COX-2 contributes to neuronal injury developing after SE, but inhibition of COX-2 is no effective means to modify epileptogenesis.
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Experimental neurology · Jul 2010
Estrogen effects on pain sensitivity and neuropeptide expression in rat sensory neurons.
While a number of chronic pain conditions are much more prevalent in women than men, the role of estrogen in regulating nociception remains unclear. Estrogen receptors (ER) are known to be expressed in various parts of the nociceptive pathway, including in the small-sized primary sensory neurons of the dorsal root ganglion (DRG). This study evaluated the effects of long term estrogen replacement on pain sensitivity and neuropeptide expression in the DRG of female Sprague Dawley rats. ⋯ We also evaluated the development of mechanical allodynia after partial sciatic nerve injury and found that both ovx and ovx+E animals developed significant allodynia within a week of the partial nerve injury, which continued for at least one month. The estrogen-treated animals showed a partial amelioration of the extent of the allodynia at 2 weeks post injury. Overall, the results suggest that estrogen has significant anti-nociceptive actions that can be directly correlated with changes in expression of two peptides in the small nociceptive ERalpha expressing neurons of the DRG.
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Experimental neurology · Jul 2010
Intrathecal injection of carbenoxolone, a gap junction decoupler, attenuates the induction of below-level neuropathic pain after spinal cord injury in rats.
The most common type of chronic pain following spinal cord injury (SCI) is central neuropathic pain and SCI patients typically experience mechanical allodynia and thermal hyperalgesia. The present study was designed to examine the potential role of astrocyte gap junction connectivity in the induction and maintenance of "below-level" neuropathic pain in SCI rats. We examined the effect of intrathecal treatment with carbenoxolone (CARB), a gap junction decoupler, on SCI-induced bilateral thermal hyperalgesia and mechanical allodynia during the induction phase (postoperative days 0 to 5) and the maintenance phase (days 15 to 20) following T13 spinal cord hemisection. ⋯ In contrast, CARB treatment during the maintenance phase had no effect on the established thermal hyperalgesia and mechanical allodynia nor on spinal GFAP expression or the number of pNR1-ir cell profiles. These results indicate that gap junctions play a critical role in the activation of astrocytes distant from the site of SCI and in the subsequent phosphorylation of NMDA receptors in the lumbar spinal cord. Both of these processes appear to contribute to the induction of bilateral below-level pain in SCI rats.
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Experimental neurology · Jun 2010
Ventral periaqueductal grey stimulation alters heart rate variability in humans with chronic pain.
The midbrain periaqueductal grey (PAG) area is important for both pain modulation and cardiovascular control via the autonomic nervous system (ANS). While changes in blood pressure dependent upon dorsal or ventral electrode positioning have been described with PAG deep brain stimulation (DBS), little is known mechanistically about the relationships between pain and cardiovascular regulation in humans. Heart rate variability (HRV) is an established measure of cardiovascular regulation, and an index of autonomic function. ⋯ Ventral PAG DBS may increase parasympathetic activity to reduce pain via anatomical connections distinct from dorsal PAG DBS, which may act by sympathetic mechanisms.