Epidural and Intrathecal Drug Delivery in Rats and Mice for Experimental Research: Fundamental Concepts, Techniques, Precaution, and Application

Abstract

Epidural and intrathecal routes are the most effective drug administration methods for pain management in clinical and experimental medicine to achieve quick results, reduce required drug dosages, and overcome the adverse effects associated with the oral and parenteral routes. Beyond pain management with analgesics, the intrathecal route is more widely used for stem cell therapy, gene therapy, insulin delivery, protein therapy, and drug therapy with agonist, antagonist, or antibiotic drugs in experimental medicine. However, clear information regarding intrathecal and epidural drug delivery in rats and mice is lacking, despite differences from human medicine in terms of anatomical space and proximity to the route of entry. In this study, we discussed and compared the anatomical locations of the epidural and intrathecal spaces, cerebrospinal fluid volume, dorsal root ganglion, techniques and challenges of epidural and intrathecal injections, dosage and volume of drugs, needle and catheter sizes, and the purpose and applications of these two routes in different disease models in rats and mice. We also described intrathecal injection in relation to the dorsal root ganglion. The accumulated information about the epidural and intrathecal delivery routes could contribute to better safety, quality, and reliability in experimental research.

Rat Model: Intrathecal Lipid for Total Spinal BlockInduced Hemodynamic Instability

“…We administered bupivacaine at a dosage of 0.5 µl/g, roughly 8-10 times the 0.03-0.06 µl/kg bupivacaine dose used for spinal anesthesia in rat studies. 15,16 In the literature, we were unable to find any information on intrathecal lipid administration. The 20% lipid treatments referenced in studies equated to the local anesthetic amount according to the lipid sink theory.…”

Ultrasound as a reliable guide for lumbar intrathecal injection in rats: A pilot study

“…Firstly, it is cheap and fast, without needing to perform the time-consuming laminectomy. It does not impose surgical stress on the study models and does not need the expensive indwelling catheter [1]. Placement of a catheter also induces immune reactions and has risk for spinal cord trauma, developing idiopathic hemorrhage or abscesses [9].…”

“…Intrathecal drug administration is the most common route to deliver drugs into the central nervous system, overcoming the blood-brain and blood-spinal cord barriers. Two main intrathecal administration techniques in animal study are acute needle puncture and chronic catheter implantation [1]. Acute needle puncture is a simpler and less invasive procedure compared to chronic catheter implantation procedures, which need surgery and are also costly.…”