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Minimally invasive technique for intrathecal administration of morphine in rats: practicality and antinociceptive
Aurelie Anic Thomas1, Johann Detilleux2, Charlotte Friederike Sandersen2
11 Medical School, University of Newcastle, Newcastle upon Tyne, UK.
Abstract:
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: FiSevo = 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 FiSevo 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.
Insights
A new, minimally invasive technique for intrathecal (IT) morphine administration in rats was developed. This method provides effective analgesia with reduced opioid doses, minimizing experimental interference.
Area of Science:
- Veterinary Medicine
- Pharmacology
- Neuroscience
Background:
- Intrathecal (IT) administration of morphine can reduce dosage and minimize experimental interference.
- Previous IT methods are often invasive, limiting their widespread use.
- A refined, minimally invasive technique is needed for IT drug delivery in research animals.
Purpose of the Study:
- To describe a simple, minimally invasive transcutaneous lumbosacral puncture technique for IT morphine administration in rats.
- To evaluate the antinociceptive efficacy of IT morphine compared to subcutaneous administration and other analgesics.
- To assess the safety and feasibility of the described IT administration technique.
Main Methods:
- Rats (n=28) were anesthetized and randomly assigned to receive IT morphine (0.2 mg/kg), subcutaneous (SC) morphine (3 mg/kg), SC buprenorphine (0.05 mg/kg), or SC/IT saline.
- A direct transcutaneous lumbosacral puncture with a 25G needle was used for IT injections.
- Antinociception was assessed by recording gross purposeful movement (GPM) in response to thermal nociceptive stimuli under varying anesthetic depths.
Main Results:
- The IT morphine administration technique was easily performed with an 82% first-attempt success rate and no complications.
- IT morphine demonstrated antinociceptive effects comparable to SC morphine and SC buprenorphine.
- No significant rostral spinal spread of IT morphine was detected.
Conclusions:
- This report details a refined, effective, and minimally invasive technique for IT morphine administration in rats.
- The IT route allows for effective analgesia with significantly lower doses than systemic administration.
- This technique minimizes potential opioid-related interference with experimental outcomes in research protocols.
