title: Targeting brain-derived neurotrophic factor in the medial thalamus for the treatment of central poststroke pain in a rodent model.
abstract: Approximately 7% to 10% of patients develop a chronic pain syndrome after stroke. This chronic pain condition is called central poststroke pain (CPSP). Recent studies have observed an abnormal increase in the secretion of brain-derived neurotrophic factor (BDNF) in spinal cord tissue after spinal cord injury. An animal model of CPSP was established by an intrathalamus injection of collagenase. Mechanical and thermal allodynia was induced after lesions of the thalamic ventral basal complex in rats. Four weeks after the injection, the number of neurons decreased, the number of astrocytes, microglia, and P2X4 receptors increased, and BDNF mRNA expression increased in the brain lesion area. Nociceptive activity in the medial thalamus (MT) and the coherence coefficient of spontaneous field potential oscillations in the anterior cingulate cortex were enhanced in CPSP animals, and these enhancements were blocked by an acute injection of TrkB-Fc and TrkB antagonist Tat Cyclotraxin-B. Instead of being inhibited by the γ-aminobutyric acid (GABA) system in normal rats, multiunit activity in the MT was enhanced after a microinjection of muscimol, a GABAA receptor agonist, in CPSP animals. After CPSP, BDNF expression was enhanced in the MT, whereas the expression of GABAA channels and the cotransporter KCC2 decreased in the same area. These findings suggest that neuronal plasticity in the MT that was induced by BDNF overexpression after the thalamic lesion was a key factor in CPSP.
authors.affiliation: Neuroscience, Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan.
authors.forename: Hsi-Chien
authors.initials: HC
authors.lastname: Shih
authors.forename: Yung-Hui
authors.initials: YH
authors.lastname: Kuan
authors.forename: Bai-Chung
authors.initials: BC
authors.lastname: Shyu
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D008297:Male; D020645:Mediodorsal Thalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D009118:Muscimol / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D059408:Pain Management / Q000379:methods*; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000037:antagonists & inhibitors*; D020521:Stroke / Q000150:complications / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D058785:GABA-A Receptor Agonists; D010456:Peptides, Cyclic; C554840:cyclotraxin-B; D009118:Muscimol; D020813:Receptor, trkB