Post-stroke pain hypersensitivity induced by experimental thalamic hemorrhage in rats is region-specific and demonstrates limited efficacy of gabapentin  

作　　者：Fei Yang Han Fu Yun-Fei Lu Xiao-Liang Wang Yan Yang Fan Yang Yao-Qing Yu Wei Sun Jia-Shuang Wang Michael Costigan Jun Chen 

机构地区：[1]Institute for Biomedical Sciences of Pain,Tangdu Hospital,The Fourth Military Medical University [2]Key Laboratory of Brain Stress and Behavior,PLA [3]Nerve Injury and Repair Center,Beijing Institute for Brain Disorders [4]Department of Pain Medicine,Guangzhou Red Cross Hospital [5]Department of Anesthesiology,Perioperative and Pain Medicine,Boston Children’s Hospital,Boston,MA,USA [6]Department of Neurology,Boston Children’s Hospital,Boston,MA,USA

出　　处：《Neuroscience Bulletin》2014年第6期887-902,共16页神经科学通报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China (81171049);the National Basic Research Development Program of China (2011CB504100,2013CB835100 and 2013BAI04B04)

摘　　要：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 Ca2＋ 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 hfor 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.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 Ca2＋ 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 hfor 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.

关 键 词：central post-stroke pain intracerebral hemorrhage intra-thalamic collagenase injection mechanical pain hypersensitivity gabapentinoids anti-allodynic effect 

分 类 号：R743.3[医药卫生—神经病学与精神病学]