title: Pain evaluation and response to buprenorphine in rats subjected to sham middle cerebral artery occlusion.
abstract: Appropriate and efficacious use of analgesics in rodents must be balanced judiciously between animal needs and research objectives. A concern in many studies is that analgesia will confound experimental outcome or interpretation. Accordingly, determining whether rats subjected to surgical protocols show evidence of pain is important if we are to provide rational postoperative analgesia without compromising experimental objectives. The goal of this study was to evaluate both subjective and objective measures for pain evaluation in male Wistar rats subjected to sham middle cerebral artery occlusion (MCAO) surgery and to determine whether buprenorphine would be an appropriate analgesic in this surgical model. Male Wistar rats underwent a sham 2-h MCAO by the intraluminal filament technique followed by 22-h of recovery. Animals were randomly assigned to one of three postoperative treatment groups: vehicle only (VH; vehicle subcutaneously [s.c.] + plain jello orally), low-dose buprenorphine (LB; 0.05 mg/kg s.c. _ 0.25 mg/kg drug-in-jello orally), and high-dose buprenorphine (HB; 0.5 mg/kg s.c. + 0.25 mg/kg drug-in-jello orally). Animals received subcutaneous treatments prior to anesthetic recovery and approximately 18-h later. Jello treatments were given once at the end of the surgery day. We modified a previously published behavioral scoring system which is based on subjective and objective measures for pain evaluation. All animals were evaluated for pain before sham surgery (baseline) and at 3-, 18-, and 22-h postoperatively by observers who were blinded to treatment group. Brains were removed at 22-h after surgery and evaluated by 2,3,5-triphenyltetrazolium chloride staining to confirm lack of brain injury from the sham procedure. Sham intraoperative physiological variables were equivalent among treatment groups. Baseline assessment scores were zero for all groups. Postoperatively, all treatment groups showed elevated assessment scores relative to baseline values. Buprenorphine at the tested doses did not markedly reduce total assessment scores postoperatively relative to those in vehicle-treated animals. Further evaluation of rodent postoperative pain and response to analgesia is needed if we are to formulate a sound scientific approach to animal management in protocols requiring surgical manipulations.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, 600 North Wolfe Street, Blalock 1408, Baltimore, Maryland 21287, USA.
authors.forename: Jodi H
authors.initials: JH
authors.lastname: Kirsch
authors.forename: Judith A
authors.initials: JA
authors.lastname: Klaus
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Blizzard
authors.forename: Patricia D
authors.initials: PD
authors.lastname: Hurn
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Murphy
mesh_terms: D000284:Administration, Oral; D000698:Analgesia / Q000379:methods / Q000662:veterinary*; D000701:Analgesics, Opioid; D000818:Animals; D002047:Buprenorphine; D002536:Cerebral Arteries / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D008297:Male; D013511:Minor Surgical Procedures / Q000009:adverse effects / Q000662:veterinary*; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000503:physiopathology / Q000517:prevention & control / Q000662:veterinary*; D051381:Rats; D017208:Rats, Wistar / Q000502:physiology* / Q000601:surgery; D016037:Single-Blind Method
chemical_list: D000701:Analgesics, Opioid; D002047:Buprenorphine