title: Post-stroke pain hypersensitivity induced by experimental thalamic hemorrhage in rats is region-specific and demonstrates limited efficacy of gabapentin.
abstract: Intractable central post-stroke pain (CPSP) is one of the most common sequelae of stroke, but has been inadequately studied to date. In this study, we first determined the relationship between the lesion site and changes in mechanical or thermal pain sensitivity in a rat CPSP model with experimental thalamic hemorrhage produced by unilateral intra-thalamic collagenase IV (ITC) injection. Then, we evaluated the efficacy of gabapentin (GBP), an anticonvulsant that binds the voltage-gated Ca(2+) channel α2δ and a commonly used anti-neuropathic pain medication. Histological case-by-case analysis showed that only lesions confined to the medial lemniscus and the ventroposterior lateral/medial nuclei of the thalamus and/or the posterior thalamic nucleus resulted in bilateral mechanical pain hypersensitivity. All of the animals displaying CPSP also had impaired motor coordination, while control rats with intra-thalamic saline developed no central pain or motor deficits. GBP had a dose-related anti-allodynic effect after a single administration (1, 10, or 100 mg/kg) on day 7 post-ITC, with significant effects lasting at least 5 h for the higher doses. However, repeated treatment, once a day for two weeks, resulted in complete loss of effectiveness (drug tolerance) at 10 mg/kg, while effectiveness remained at 100 mg/kg, although the time period of efficacious analgesia was reduced. In addition, GBP did not change the basal pain sensitivity and the motor impairment caused by the ITC lesion, suggesting selective action of GBP on the somatosensory system.
authors.affiliation: Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an, 710038, China.
authors.forename: Han
authors.initials: H
authors.lastname: Fu
authors.affiliation: Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Lu
authors.affiliation: Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an, 710038, China.
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Nerve Injury and Repair Center, Beijing Institute for Brain Disorders, Beijing, 100069, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Nerve Injury and Repair Center, Beijing Institute for Brain Disorders, Beijing, 100069, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an, 710038, China.
authors.forename: Yao-Qing
authors.initials: YQ
authors.lastname: Yu
authors.affiliation: Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an, 710038, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Pain Medicine, Guangzhou Red Cross Hospital, Guangzhou, 510220, China.
authors.forename: Jia-Shuang
authors.initials: JS
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, MA, USA.|Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Costigan
authors.affiliation: Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China. junchen@fmmu.edu.cn.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an, 710038, China. junchen@fmmu.edu.cn.|Nerve Injury and Repair Center, Beijing Institute for Brain Disorders, Beijing, 100069, China. junchen@fmmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
mesh_terms: D000588:Amines / Q000494:pharmacology / Q000627:therapeutic use*; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D000077206:Gabapentin; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D020300:Intracranial Hemorrhages / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D013788:Thalamus / Q000473:pathology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin