title: Continual systemic infusion of lidocaine provides analgesia in an animal model of neuropathic pain.
abstract: We examined whether continual constant-rate infusion of lidocaine would provide analgesia during the initial post-injury phase in the chronic constriction injury model of neuropathic pain. Male Sprague-Dawley rats were divided into control and ligated groups and infused with saline or lidocaine (0.15, 0.33, 0.67, and 1.3mg/kg/h) via subcutaneously implanted Alzet((R)) osmotic minipumps. Thermal withdrawal latencies were obtained prior (Day 0) and 3 days after loose sciatic ligation and pump implantation surgery. Ligated animals receiving lidocaine at 0.67 or 1.3mg/kg/h exhibited no change in withdrawal latency on Day 3 after surgery, indicating that lidocaine at these doses prevented the development of thermal hyperalgesia as a sign of neuropathic pain. In contrast, ligated animals treated with saline or lidocaine at 0.15 or 0.33mg/kg/h exhibited hyperalgesia on Day 3 after surgery, indicating that these lower doses of lidocaine failed to provide analgesia. Control animals treated with saline or any of the lidocaine doses exhibited no change in withdrawal latencies between Day 0 and Day 3. In a separate group of ligated animals, lidocaine infusion (0.67mg/kg/h) that was started 24h after sciatic ligation surgery reversed the already present thermal hyperalgesia. Average plasma lidocaine concentrations were 0.11, 0.36, and 0.45microg/ml for animals receiving 0.33, 0.67 and 1.3mg/kg/h of lidocaine, respectively. These results suggest that continual systemic infusion of lidocaine prevents or reverses the development of neuropathic pain following chronic constriction injury. These results add to the increasing body of evidence supporting the therapeutic value of preemptive and post-operative lidocaine administration for the relief of neuropathic pain.
authors.affiliation: Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Drive, Madison, WI 53706-1102, USA Department of Comparative Biosciences, University of Wisconsin, 2015 Linden Drive, Madison, WI 53706-1102, USA.
authors.forename: Lesley J
authors.initials: LJ
authors.lastname: Smith
authors.forename: Andre
authors.initials: A
authors.lastname: Shih
authors.forename: Gordana
authors.initials: G
authors.lastname: Miletic
authors.forename: Vjekoslav
authors.initials: V
authors.lastname: Miletic
mesh_terms: D000779:Anesthetics, Local / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy; D015918:Infusion Pumps, Implantable; D008012:Lidocaine / Q000097:blood / Q000494:pharmacology*; D008026:Ligation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012585:Sciatica / Q000188:drug therapy*
chemical_list: D000779:Anesthetics, Local; D008012:Lidocaine