title: Intrathecal ketamine and pregabalin at sub-effective doses synergistically reduces neuropathic pain without motor dysfunction in mice.
abstract: 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.
authors.affiliation: Department of Anesthesiology and Pain Medicine, School of Medicine, Chonbuk National University, Jeonju 561-712, South Korea.
authors.forename: Hyung Sun
authors.initials: HS
authors.lastname: Lim
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Jae-Gyun
authors.initials: JG
authors.lastname: Choi
authors.forename: Young Kwon
authors.initials: YK
authors.lastname: Ko
authors.forename: Yong Sup
authors.initials: YS
authors.lastname: Shin
authors.forename: Beyong Hwa
authors.initials: BH
authors.lastname: Jeon
authors.forename: Jin Bong
authors.initials: JB
authors.lastname: Park
authors.forename: Jang-Hern
authors.initials: JH
authors.lastname: Lee
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Kim
mesh_terms: D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D004195:Disease Models, Animal; D004357:Drug Synergism; D006930:Hyperalgesia / Q000188:drug therapy*; D007278:Injections, Spinal; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009048:Motor Skills / Q000187:drug effects; D009437:Neuralgia / Q000188:drug therapy*; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000700:Analgesics; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D007649:Ketamine