Minimally invasive technique for intrathecal administration of morphine in rats: practicality and antinociceptive properties

The intrathecal (IT) route of administration represents a means to reduce the dose of morphine administered for analgesia, potentially minimizing interactions between opioid effects and experimental outcomes. Perceived technical difficulty, and previously described invasive methods, may limit its use. This report describes a minimally invasive technique for IT administration of morphine by direct transcutaneous lumbosacral puncture in rats; and assesses antinociceptive properties of morphine in anaesthetized rats. Rats ( n = 28) anaesthetized with sevoflurane (inspired fraction of sevoflurane: F_iSevo = 2.4%) were randomly allocated to receive: IT morphine (0.2 mg/kg); subcutaneous (SC) morphine (3 mg/kg); SC buprenorphine (0.05 mg/kg); or SC or IT sodium chloride (NaCl). After a wash-in period (40 min), thermal nociceptive stimuli were applied at nine locations corresponding to different rostrocaudal dermatomes of the rat. Nociceptive stimulation cycles were repeated at all locations after successive decrement of F_iSevo by 15%. Presence or absence of gross purposeful movement (GPM) was recorded for each individual stimulation. IT injection of morphine by direct puncture with a 25 G hypodermic needle is easily performed (successful first attempt: 82%) without complications. IT morphine reduced the frequency of GPM following nociceptive thermal stimulation in a way comparable with SC buprenorphine or morphine. It was not possible to delimit any rostral spinal spread of morphine. This report describes a refined and effective technique of administering morphine IT in rats using readily available materials. IT doses being markedly smaller than the systemic equivalent, analgesia could be provided whilst minimizing the potential interactions of non-analgesic opioid effects with research protocols.