title: Buprenorphine for pain relief in mice: repeated injections vs sustained-release depot formulation.
abstract: Sustained-release formulations of analgesic drugs are promising alternatives to repeated drug injections. Here, we compared a sustained-release formulation of buprenorphine (SB, 2.2 mg/kg) with a standard protocol of three injections of buprenorphine (Temgesic, 0.1 mg/kg/8 h) in mice. Buprenorphine serum concentration and analgesic action (thermal sensitivity) were determined in healthy mice. Additionally, the pain relief properties of both protocols were assessed after laparotomy using physiological and ethological measures of pain and recovery. Serum concentrations and thermal sensitivity tests indicated duration of action of at least 4 h (but less than 8 h) with the Temgesic protocol, and 24-48 h with SB. Behavioural and clinical parameters indicated at least partial pain relief after surgery for both protocols. Observed side-effects of buprenorphine independent of the protocol were increased activity, disturbed circadian rhythm and several abnormal behaviours. A tendency for decreased food and water intake as well as body weight reduction was also seen. Body weight decreased significantly in animals that received three injections of Temgesic, regardless of whether surgery was performed or not (P = 0.015; P = 0.023), hinting at a stress response towards this repeated intervention. In conclusion, an application interval of 8 h (Temgesic) appears too long and might lead to repeated periods with insufficient analgesia in animals undergoing lasting and/or substantial pain after surgery. In comparison to the standard protocol, SB provided a long-lasting, assured analgesia without possible stressful repeated injections in a standard surgical model, with only limited and acceptable behavioural side-effects.
authors.affiliation: Division of Surgical Research, Centre for Clinical Research, University Hospital Zurich, University of Zurich, Zurich, Switzerland Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland paulin.jirkof@usz.ch.
authors.forename: P
authors.initials: P
authors.lastname: Jirkof
authors.affiliation: HumanVet Sàrl, Lausanne, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Tourvieille
authors.affiliation: Division of Trauma Surgery, Centre for Clinical Research, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Cinelli
authors.affiliation: Division of Surgical Research, Centre for Clinical Research, University Hospital Zurich, University of Zurich, Zurich, Switzerland Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Arras
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D002047:Buprenorphine / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D005260:Female; D006358:Hot Temperature / Q000009:adverse effects; D007279:Injections, Subcutaneous; D007813:Laparotomy; D051379:Mice; D008810:Mice, Inbred C57BL; D010146:Pain / Q000188:drug therapy*; D059408:Pain Management / Q000379:methods*; D010147:Pain Measurement
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D002047:Buprenorphine
keywords: analgesia; buprenorphine; mouse; pain; sustained release