Intraneural injection

What is the primary receptor target by which local anesthetics exert their effects?

A.Voltage-gated calcium channels
B. Voltage-gated potassium channels
C. Voltage-gated sodium channels
D. Voltage-gated proton channels

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Correct answer: C


Axons are surrounded by connective tissue called the endoneurium.  The interstitial fluid inside the endoneurium of the brachial plexus roots consists of cerebral spinal fluid.  These roots are surrounded by a dural sleeve, which connects to the dura matter, and fascicles within the nerve roots are extensions of the spinal nerve.  Groups of axons together form a fascicle, which is surrounded by a membrane called the perinerium.  This perineurium forms a physical and chemical barrier.  Currently, it is believed that advancing a needle within the perinerium and injecting local anesthetic results in neurologic injury and should be avoided.  This has been referred to as an ‘intraneural intrafascicular’ injection.  Unfortunately, current popular ultrasound technology does not have the resolution to discern the perineural layer accurately.  Fascicles join to form bundles, which are surrounded by a fibroadipose tissue called the epineurium.  The epineurium consists of 2 parts, an interfascicular and an outer epineurium.  Injection within the epineurium is also considered an ‘intraneural injection’.  Current popular ultrasound technology does not have the resolution to discern the epineurium, and an injection within the epineurium but outside the perinerium can only be noted once the proceduralist injects the solution (increase in cross-sectional diameter of the nerve by more than 15%, separation of the fascicles or fascicular bundles, diffusion of the local anesthetic in a proximal and distal location).  There also appears tobe a paraneural sheath (also been referred to as ciriumneural sheath) that surrounds the epineurium.  This sheath has also been referred to as a gliding apparatus.  An injection between the paraneural (circumneural) sheath and the epineurium has been considered the safest location for local anesthetic deposition in order to not damage the nerve integrity while offering a slower onset yet still effective nerve block.


Sala-Blanch X, Vandepitte C, Laur JJ, Horan P, Xu D, Reina MA, Karmakar MK, Clark TB, Hadzic A.  “A practical review of perineural versus intraneural injection: a call for standard nomenclature.” Int Anesthesiology Clinics;2011:49(4):1-12

Neal JM, Barrington MJ, Brull R, Hadzic A, Heble JR, Horlocker TT, Huntoon MA, Kopp SL, Rathmell JP, Watson JC.  “The second ASRA practice advisory on neurologic complications associated with regional anesthesia and pain medicine: Executive Summary 2015.” 

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