A fully implanted drug delivery system for peripheral nerve blocks in behaving animals

Abstract

Inhibiting peripheral nerve function can be useful for many studies of the nervous system or motor control. Accomplishing this in a temporary fashion in animal models by using peripheral nerve blocks permits studies of the immediate effects of the loss, and/or any resulting short-term changes and adaptations in behavior or motor control, while avoiding the complications commonly associated with permanent lesions, such as sores or self-mutilation. We have developed a method of quickly and repeatedly inducing temporary, controlled motor deficits in rhesus macaque monkeys via a chronically implanted drug delivery system. This assembly consists of a nerve cuff and a subdermal injection dome, and has proved effective for delivering local anesthetics directly to peripheral nerves for many months. Using this assembly for median and ulnar nerve blocks routinely resulted in over 80% losses in hand and wrist strength for rhesus monkeys. The assembly was also effective for inducing ambulatory motor deficits in rabbits through blocks of the sciatic nerve. Interestingly, while standard anesthetics were sufficient for the rabbit nerve blocks, the inclusion of epinephrine was essential for achieving significant motor blockade in the monkeys.

Figure 1

A: Nerve cuff, cannula, and injection port used in rabbit experiments. B: The appearance of the injection dome beneath the skin in the upper arm of monkey M2. C: A nerve cuff around the rabbit sciatic nerve. The 3 stimulating wires are visible in the foreground. D-E show the implantation of a cuff around the ulnar nerve in M2 before (D) and after (E) the silastic has been shaped into a tube around the nerve.

Figure 2

Effect of peripheral nerve block on sciatic nerve conduction for rabbit R5. Injection of 2% lidocaine substantially decreased conduction, shown as the reciprocal of the normalized current strength required to evoke a contraction. Combination with epinephrine (1:100,000) further increased the effect, while saline had very little effect.

Figure 3

Effects of lidocaine PNBs of the rabbit sciatic nerve across post-implantation time. The size of the markers is proportional to the dose of lidocaine (volume * concentration). Open circles mark saline injections, and correspond to the volume of a 2% lidocaine injection. Injections that included epinephrine are marked with an “E”.

Figure 4

Effects on palmar grip strength of lidocaine PNBs of the median and ulnar nerves for rhesus monkey across post-implantation time. Open circles mark those injections without epinephrine, which were largely ineffective. Tests beyond 40 days for M1-R included only median nerve block. Symbols denoting experiments in which the dose was split into two injections are circled in black.