Experimental neurology
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Experimental neurology · Oct 2008
Comparative StudyActivation of p38 MAP kinase is involved in central neuropathic pain following spinal cord injury.
Recent work regarding chronic central neuropathic pain (CNP) following spinal cord injury (SCI) suggests that activation of key signaling molecules such as members of the mitogen activated protein kinase (MAPK) family play a role in the expression of at-level mechanical allodynia. Previously, we have shown that the development of at-level CNP following moderate spinal cord injury is correlated with increased expression of the activated (and thus phosphorylated) forms of the MAPKs extracellular signal related kinase and p38 MAPK. The current study extends this work by directly examining the role of p38 MAPK in the maintenance of at-level CNP following spinal cord injury. ⋯ Immunocytochemical analyses indicate that the increases in p38 MAPK activation occurred in astrocytes, microglia, and dorsal horn neurons in the spinal cord rostral to the site of injury. Inhibiting the enzymatic activity of p38 MAPK dose dependently reverses the behavioral expression of at-level mechanical allodynia and also decreases the hyperexcitability seen in thoracic dorsal horn neurons after moderate SCI. Taken together, these novel data are the first to demonstrate causality that increased activation of p38 MAPK in multiple cell types play an important role in the maintenance of at-level CNP following spinal cord injury.
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Experimental neurology · Oct 2008
Comparative StudyDepletion of peptidergic innervation in the gastric mucosa of streptozotocin-induced diabetic rats.
Autonomic neuropathy affecting the gastrointestinal system is a major presentation of diabetic neuropathy. Changes in the innervation of gastric mucosa or muscle layers can contribute to gastrointestinal symptoms. The present study investigated this issue by quantitatively analyzing the immunohistochemical patterns of the gastric innervation in rats with streptozotocin (STZ)-induced diabetes. ⋯ Reverse transcription-polymerase chain reaction (RT-PCR) showed that the expression levels of SP and CGRP mRNA in the thoracic dorsal root ganglia were similar between diabetic and control animals (p>0.05). Qualitative and quantitative ultrastructural examinations on the gastric mucosa documented unmyelinated nerve degeneration. These results suggest the existence of gastric sensory neuropathy in STZ-induced diabetes, and this pathology provides a foundation for understanding diabetic gastropathy.
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Experimental neurology · Oct 2008
Comparative StudyNeurotrophin-3 significantly reduces sodium channel expression linked to neuropathic pain states.
Neuropathic pain resulting from chronic constriction injury (CCI) is critically linked to sensitization of peripheral nociceptors. Voltage gated sodium channels are major contributors to this state and their expression can be upregulated by nerve growth factor (NGF). We have previously demonstrated that neurotrophin-3 (NT-3) acts antagonistically to NGF in modulation of aspects of CCI-induced changes in trkA-associated nociceptor phenotype and thermal hyperalgesia. ⋯ Intrathecal infusion of NT-3 significantly attenuates neuronal expression of Na(v)1.8 and Na(v)1.9 mRNA contralateral and most notably, ipsilateral to CCI, with a similar impact on relative protein expression at the level of the neuron and constricted nerve. We also observe reduced expression of the common neurotrophin receptor p75 in response to CCI that is not reversed by NT-3 in small to medium sized neurons and may confer an enhanced ability of NT-3 to signal via trkA, as has been previously shown in other cell types. These findings are consistent with an analgesic role for NT-3.
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Experimental neurology · Oct 2008
Comparative StudySerotonergic neurotransmission in the dorsal raphe nucleus recruits in situ 5-HT(2A/2C) receptors to modulate the post-ictal antinociception.
The post-ictal immobility syndrome is followed by a significant increase in the nociceptive thresholds in animals and humans. The aim of this study was to assess the involvement of the dorsal raphe nucleus (DRN) in the post-ictal antinociception. The second aim was to study the role of serotonergic intrinsic mechanisms of the DRN in this hypo-algesic phenomenon. ⋯ Ketanserin is an antagonist with large affinity for 5-HT(2A/2C) serotonergic receptors, which, in this case, caused a significant decrease in the tail-flick latencies in seizing animals, compared to controls after the first 20 min following tonic-clonic convulsive reactions. These results indicate that serotonergic neurotransmission of the DRN neuronal clusters is involved in the organization of the post-ictal hypo-algesia. The 5-HT(2A/2C) receptors of DRN neurons seem to be critically involved in the increase of nociceptive thresholds following tonic-clonic seizures.
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Experimental neurology · Sep 2008
A re-assessment of erythropoietin as a neuroprotective agent following rat spinal cord compression or contusion injury.
This study was initiated due to an NIH "Facilities of Research--Spinal Cord Injury" contract to support independent replication of published studies that appear promising for eventual clinical testing. We repeated a study reporting the beneficial effects of recombinant human erythropoietin (rhEPO) treatment after spinal cord injury (SCI). ⋯ Also, secondary changes (i.e. necrotic changes followed by cavitation) were not significantly improved with rhEPO therapy. With these results, although we cannot conclude that there will be no beneficial effect in different SCI models, we caution researchers that the use of rhEPO requires further investigation before implementing clinical trials.