Efficacy of intrathecal morphine in a model of surgical pain in rats

Auelie Thomas, Amy Miller, Johnny Roughan, Aneesa Malik, Katherine Haylor, Charlotte Sandersen, Paul Flecknell, Matthew Leach

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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. Morphinetreated 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
Original languageEnglish
Article numbere0163909
Pages (from-to)1-21
Number of pages21
JournalPLoS ONE
Issue number10
Publication statusPublished - 26 Oct 2016
Externally publishedYes


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