I am injecting intrathecally (between L5-L6) , in rats, cannabinoid analgesics and I was wondering if they can reach the brain and have effects there as well ?
Also I need to pretreat with antagonists (AM630 and Capsazepine) and was wondering how long does it take to get them cleared from spinal cord. I usually pretreat for 30min before agonist injections, is this too long or is it ok ? (we are interested in spinal effects only). I cannot inject the agonist and the antagonist simultaneously as the volume of each injection is too big to inject them one after the other (I had to dilute drugs in bigger volume in order to lower % of ethanol of solution: 20uL for antagonist and 30uL for agonist)
Yes, drugs injected intrathecally can reach the the brain and have effects there. That's why we are so careful with the dose of local anesthesia medications we inject to achieve spinal anesthesia. We intentionally want them to have effects on the lower spinal cord and not reach the brain. That's why we pay such close attention to patient positioning during and after the medication injection, as well as the type of medication, the dose of the medication, the volume of the medication, and the "baricity" or "specific gravity" of the medications we use for spinal and epidural anesthesia. All of these factors must be considered in every spinal or epidural injection.
HI Besma,
There is not a simple answer to your question. Yes, it is possible for a drug that is injected intrathecally to make it to the brain in small amounts. This and other questions you raise can be dependent on a lot of things, the volume, the concentration, the pharmacokinetics of the specific drug, the intrathecal location. You can find spinal specificity of function using intrathecal injection but you must be very careful about how you are testing this and making sure to consider all of the above. You need to investigate the pharmacokinetics of both your agonist and antagonist to determine the proper timing of multiple injections. You will also need to balance the need for multiple injections with risk and effects on stress of multiple spinal injections, anesthesia if you are using it, etc. In some instances, you can contain both agonist and antagonist in the same injection, one after the other. You would need to provide us with more specific information about your intended purpose and the drugs you intend to use, what concentrations, volumes and what you are intending to test after injection for us to give you an adequate answer.
The short answer: It depends.
The lots-of-time answer: You should probably read Spinal Drug Delivery (Tony Yaksh, editor)--definitely the Chris Bernards chapters like "Epidural and intrathecal drug movement" and the Shafers' chapter "Spinal pharmacokinetics." The book came out in 1999, so there's some information that won't be in there, but it's as good a start as you're going to find.
Yes, compounds can move from lumbar intrathecal space to the head. It's going to depend on injection volume, density/tonicity of injectate, orientation of the experimental subject--and these will interact. Antagonist clearance will be a function of distribution within the IT space (governed by the factors above) and out of the IT space (governed by other factors like lipophilicity).
Yes, Intrathecal injection of many drugs drive them supraspinally. An example is the drugs injected for chemotherapy (methotrexate and some corticosteroids) and morphine also may reach there. The time is different between drugs. Highly lipid soluble drugs may attach to spinal cord. While, water soluble drugs like morphine stay circulating for longer time and responsible for respiratory depression.
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