title: Efficacy of Intrathecal Morphine in a Model of Surgical Pain in Rats.
abstract: Concerns over interactions between analgesics and experimental outcomes are a major reason for withholding opioids from rats undergoing surgical procedures. Only a fraction of morphine injected intravenously reaches receptors responsible for analgesia in the central nervous system. Intrathecal administration of morphine may represent a way to provide rats with analgesia while minimizing the amount of morphine injected. This study aimed to assess whether morphine injected intrathecally via direct lumbar puncture provides sufficient analgesia to rats exposed to acute surgical pain (caudal laparotomy).In an initial blinded, randomised study, pain-free rats received morphine subcutaneously (MSC, 3mg.kg-1, N = 6), intrathecally (MIT, 0.2mg.kg-1, N = 6); NaCl subcutaneously (NSC, N = 6) or intrathecally (NIT, N = 6). Previously validated pain behaviours, activity and Rat Grimace Scale (RGS) scores were recorded at baseline, 1, 2, 4 and 8h post-injection. Morphine-treated rats had similar behaviours to NaCl rats, but their RGS scores were significantly different over time and between treatments. In a second blinded study, rats (N = 28) were randomly allocated to one of the following four treatments (N = 7): MSC, 3mg.kg-1, surgery; MIT, 0.2mg.kg-1, surgery; NIT, surgery; NSC, sham surgery. Composite Pain Behaviours (CPB) and RGS were recorded as previously. CPB in MIT and MSC groups were not significantly different to NSC group. MSC and MIT rats displayed significantly lower RGS scores than NIT rats at 1 and 8h postoperatively. RGS scores for MIT and MSC rats were not significantly different at 1, 2, and 8h postoperatively. Intraclass correlation value amongst operators involved in RGS scoring (N = 9) was 0.913 for total RGS score. Intrathecal morphine was mostly indistinguishable from its subcutaneous counterpart, providing pain relief lasting up to 8 hours in a rat model of surgical pain. Further studies are warranted to clarify the relevance of the rat grimace scale for assessing pain in rats that have received opioid analgesics.
authors: Comparative Biology Centre, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors: Aurelie
authors: http://orcid.org/0000-0003-1655-3278
authors: A
authors: Thomas
authors: School of Agriculture, Food and Rural Development, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors: Amy
authors: A
authors: Miller
authors: Comparative Biology Centre, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors: Johnny
authors: J
authors: Roughan
authors: Royal (Dick) School of Veterinary Studies, Edinburgh, United Kingdom.
authors: Aneesa
authors: A
authors: Malik
authors: School of Biomedical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors: Katherine
authors: K
authors: Haylor
authors: Clinique Vétérinaire Universitaire, Faculté de Médecine Vétérinaire, Université de Liège, Liège, Belgium.
authors: Charlotte
authors: C
authors: Sandersen
authors: Comparative Biology Centre, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors: Paul
authors: P
authors: Flecknell
authors: School of Agriculture, Food and Rural Development, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors: Matthew
authors: M
authors: Leach
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D007278:Injections, Spinal; D009020:Morphine / Q000494:pharmacology / Q000627:therapeutic use*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014741:Video Recording
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine