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.
Highlights
Rodents remain the most commonly used animals for fundamental science and translational medicine [1]
This study aimed to assess whether morphine injected intrathecally via direct lumbar puncture provides sufficient analgesia to rats exposed to acute surgical pain.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)
Findings from the present study suggest that administration of intrathecal morphine by percutaneous injection may represent an effective way of providing long lasting pain relief in rodents subjected to caudal laparotomy and bladder wall injection
Summary
Rodents remain the most commonly used animals for fundamental science and translational medicine [1]. Public perception and acceptance of animal models for biomedical research relies on the respect of fundamental ethical rules, such as the systematic implementation of the 3Rs: replacement, reduction and refinement [2,3,4,5]. Whilst the vast majority of rodent surgical research procedures are performed under anaesthesia, surveys indicate that the use of perioperative analgesics remains low; e.g. in less than 25% of rats undergoing surgery [7,8,9]. The main reported reasons for this are concerns over interactions with results of studies or potential negative side-effects from the analgesic themselves, or that there was no perceived need for using pain relief as a consequence of an inability to effectively recognise pain [7,8,10]
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