Abstract
Central post-stroke pain (CPSP) can occur as a result of a cerebrovascular accident in the ventral posterolateral nucleus (VPL) of the thalamus. Developing therapeutic interventions for CPSP is difficult because its pathophysiology is unclear. Here we developed and characterized a macaque model of CPSP. The location of the VPL was determined by magnetic resonance imaging (MRI) and extracellular recording of neuronal activity during tactile stimulation, after which a hemorrhagic lesion was induced by injecting collagenase type IV. Histological analysis revealed that most of the lesion was localized within the VPL. Several weeks after the injection, the macaques displayed behavioral changes that were interpreted as reflecting the development of both mechanical allodynia and thermal hyperalgesia. Immunohistochemistry revealed that microglial and astrocytic activation in the perilesional areas lasted at least 3 months after injection. The present model reproduced the symptoms of patients suffering from CPSP, in which both mechanical allodynia and thermal hyperalgesia often develop several weeks after cerebrovascular accident. Further, the long-lasting glial activation revealed here may be characteristic of primate brains following injury. The present model will be useful not only for examining the neurological changes underlying CPSP, but also for testing therapeutic interventions for CPSP.
Highlights
Central post-stroke pain (CPSP) is a chronic neuropathic pain that occurs as a result of a stroke lesion in the somatosensory pathway that includes the posterolateral region of the thalamus[1,2,3,4]
CPSP can develop after both ischemic and hemorrhagic vascular lesions[14,15,16], we focused on hemorrhagic stroke in the present study because most rodent CPSP models are created by inducing hemorrhage[17,18,19,20,21,22]; we can investigate how symptoms after thalamic damage differ between rodents and primates
We developed a primate model of CPSP based on a hemorrhagic lesion induced in the ventral posterolateral nucleus (VPL) of rhesus macaques
Summary
Central post-stroke pain (CPSP) is a chronic neuropathic pain that occurs as a result of a stroke lesion in the somatosensory pathway that includes the posterolateral region of the thalamus[1,2,3,4]. A lesion of the thalamus including the VPL was made by inducing a focal stroke Using these models, researchers have shown that a lesion around the VPL is associated with allodynia- and hyperalgesia-like behavior and have suggested that some drugs can ameliorate the symptoms. Researchers have shown that a lesion around the VPL is associated with allodynia- and hyperalgesia-like behavior and have suggested that some drugs can ameliorate the symptoms In addition to these rodent models, a primate model of CPSP, using rhesus macaques, might contribute to overcoming CPSP because it is more compatible with humans in regard to the structures and functions of brain regions suggested to be involved in pain in humans. We performed histological analyses to investigate both microglial and astrocytic activation, which is associated with the development of abnormal pain after peripheral nerve and spinal cord injury[23,24,25,26,27]
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