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Neuroscience. 2009 Jun 16;161(1):173-83. doi: 10.1016/j.neuroscience.2009.03.042. Epub 2009 Mar 24.

Development and characterization of a hemorrhagic rat model of central post-stroke pain.

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University of Toronto, Division of Anatomy, MSB 1186, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.


Stroke is the leading cause of disability in the industrialized world and it is estimated that up to 8% of stroke victims suffer from some form of central post-stroke pain (CPSP). Thalamic syndrome is form of central pain that typically results from stroke in the thalamus. In the present study, we describe the development and characterization of a rat model of thalamic CPSP. This model is based on a hemorrhagic stroke lesion in the ventral posterolateral nucleus of the thalamus, one of the reported causes of thalamic syndrome in humans. Behavioral analysis showed that animals displayed hyperesthesia in response to mechanical pinch stimulation, with sensitivity localized to the hind limb. This response appeared within 7 days of the intra-thalamic hemorrhage. Animals also showed increased thermal sensitivity in the contralateral hind limb. Histopathology indicated the presence of activated microglia adjacent to the core of hemorrhagic lesions in the thalamus. Neutrophils were confined to the hemorrhage core, indicating that they entered in the initial bleed. By 7 days, bands of activated microglia and astrocytes separated the hematoma from surviving neurons at the edge of the lesion. We did not observe any terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive neurons beyond the immediate hematoma at 1, 3, or 7 days after hemorrhage. Surviving neurons were located in the vicinity of activated microglia and astrocytes at the outer edge of the hematoma. Thus, thalamic hemorrhage produces a confined lesion that destroys the tissue within the initial bleed, with little or no neuron death beyond the hemorrhage core. Surviving neurons surrounded by activated glial cells likely contribute to neuropathic pain in this model. This thalamic hemorrhage model is useful for studying the neuropathology and physiology of thalamic syndrome, and developing therapeutics for central post-stroke pain.

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