Intrathecal Ketamine and Pregabalin at Sub-effective Doses Synergistically Reduces Neuropathic Pain without Motor Dysfunction in Mice

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  • Lim Hyung Sun
    Department of Anesthesiology and Pain Medicine, School of Medicine, Chonbuk National University
  • Kim Jae-Min
    Department of Physiology and Institute of Brain Research, School of Medicine, Chungnam National University
  • Choi Jae-Gyun
    Department of Physiology and Institute of Brain Research, School of Medicine, Chungnam National University
  • Ko Young Kwon
    Department of Anesthesiology and Pain Medicine, School of Medicine, Chungnam National University
  • Shin Yong Sup
    Department of Anesthesiology and Pain Medicine, School of Medicine, Chungnam National University
  • Jeon Beyong Hwa
    Department of Physiology and Institute of Brain Research, School of Medicine, Chungnam National University
  • Park Jin Bong
    Department of Physiology and Institute of Brain Research, School of Medicine, Chungnam National University
  • Lee Jang-Hern
    Department of Veterinary Physiology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University
  • Kim Hyun-Woo
    Department of Physiology and Institute of Brain Research, School of Medicine, Chungnam National University

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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.

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