Intrathecal Ketamine and Pregabalin at Sub-effective Doses Synergistically Reduces Neuropathic Pain without Motor Dysfunction in Mice
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概要
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Peripheral or central nerve injury often leads to neuropathic pain. Although ketamine and pregabalin are first line options for the treatment of neuropathic pain, their clinical application is limited due to side effects such as sedation, dizziness and somnolence. We designed this study to determine whether the intrathecal (i.t.) co-treatment with ketamine and pregabalin at sub-effective low doses would elicit a sufficient pain relief without producing side effect in a neuropathic pain mouse model. At day 7 after chronic constriction injury (CCI) of sciatic nerve, dose dependent effects of i.t. ketamine (3, 10, 30, 100 µg) or i.t. pregabalin (10, 30, 100 µg) on mechanical allodynia and thermal hyperalgesia were measured. For combination treatment, 3 or 10 µg of ketamine and 30 µg of pregabalin were selected because these doses of drugs were not effective on neuropathic pain. Interestingly, combined i.t. treatment groups (ketamine 3 µg+pregabalin 30 µg and ketamine 10 µg+pregabalin 30 µg) produced strong analgesia on neuropathic pain although these doses of ketamine and pregabalin alone are not effective. Moreover, rota rod test revealed that normal motor function was not affected by combined treatment while i.t. ketamine at doses above 10 µg showed a significant motor dysfunction. Results of this study suggested that i.t. co-treatment with ketamine and pregabalin at sub-effect low doses may be a useful therapeutic method for the treatment of neuropathic pain patients.
- 公益社団法人 日本薬学会の論文
著者
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Lee Jang-hern
Department Of Veterinary Physiology College Of Veterinary Medicine And Bk21 Program For Veterinary S
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Shin Yong
Department Of Anesthesiology And Pain Medicine Chungnam National University Hospital
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Lim Hyung
Department Of Chemistry Faculty Of Science The Johns Hopkins University
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Kim Hyun-woo
Department Of Biology Pusan National University
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Ko Young
Department Of Anatomy Seoul National University College Of Medicine
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Park Jin
Department of Advanced Materials Science and Engineering, Sungkyunkwan University, Suwon, Gyeonggi 440-746, Republic of Korea
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Lee Jang-Hern
Department of Veterinary Physiology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University
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Park Jin
Department of Physiology and Institute of Brain Research, School of Medicine, Chungnam National University
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Choi Jae-Gyun
Department of Physiology and Institute of Brain Research, School of Medicine, Chungnam National University
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Kim Jae-Min
Department of Physiology and Institute of Brain Research, School of Medicine, Chungnam National University
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Jeon Beyong
Department of Physiology and Institute of Brain Research, School of Medicine, Chungnam National University
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Lim Hyung
Department of Anesthesiology and Pain Medicine, School of Medicine, Chonbuk National University
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Kim Hyun-Woo
Department of Physiology and Institute of Brain Research, School of Medicine, Chungnam National University
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