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ESRA19-0616 New concepts in physiopathology of the nerve lesions: intraneural injection microanatomy in humans and animal models
  1. MA Reina1,
  2. OC Nin2,
  3. A Oviedo-Baena2,
  4. LT Le-Wendling2,
  5. Y Zasimovich2,
  6. A Server3 and
  7. A Boezaart2,3,4
  1. 1CEU San Pablo University School of Medicine, Department of Anesthesiology, Madrid-Montepríncipe University Hospital, Madrid, Spain
  2. 2Division of Acute and Perioperative Pain Medicine, Department of Anesthesiology and the Department of Orthopaedic Surgery, University of Florida College of Medicine, Gainesville, Florida, USA
  3. 3Department of Anesthesiology, Hospital Universitari Vall d’Hebron, Barcelona, Spain
  4. 4Alon P. Winnie Research Institute, Gainesville, Florida and Still Bay South Africa, Madrid, Spain


It has generally been accepted that intrafascicular spread of local anesthetic solution is the major cause of severe and devastating neurological complications after intraneural local anesthetic injection.1 Furthermore, the validity of the human extrapolation of animal experiment conclusions has been recently disputed.2 After performing deliberate intraneural injections using StimuPlex D, 22-guage (15° bevel) needles with a new marker (heparinized erythrocytes)3 under ultrasound guidance mimicking clinical practice, and creating the worst possible conditions for regional block, we microscopically analyzed the longitudinal and circumferential spread in the extrafascicular and intrafascicular compartments in human sciatic and median nerves. This was also done in sciatic nerves of dogs, pigs and sheep. Swelling of the nerves confirmed intraneural injection.

Extrafascicular spread was seen in all human and animal samples outside the perineurium, intermingled between the interfascicular adipocytes except in extrafascicular compartments where adipocytes were absent. Intrafascicular spread was absent in almost all samples. the marker was also observed filling the entire thickness of perineurium between the perineurium cellular layers. Erythrocytes were not found inside the endoneurium of most of the fascicles examined.

Intrafascicular intraneural injection has been entertained as possible option in a few cases, but we were surprises to find no evidence of intrafascicular spreading in the vast majority of fascicles. the compact endoneural structure and the absence of endoneural spaces4–5 probably explain our findings and may help to understand the relatively low number of neurological complications caused by peripheral regional anesthesia considering the high number of blocks that are performed and the high number of intraneural injections that may be done intentionally or unintentionally.


  1. Brull R, Hadzic A, Reina MA, Barrington MJ: Pathophysiology and etiology of nerve injury following peripheral nerve blockade. Reg Anesth Pain Med 2015;40:479–90.

  2. Server A, Reina MA, Boezaart AP, Prats-Galino A, Esteves Coelho M, Sala-Blanch X. Microanatomical nerve architecture of six mammalian species: Is trans-species translational anatomic extrapolation valid?Reg Anesth Pain Med 2018;43:496–501.

  3. Reina MA, Boezaart AP, Sala-Blanch X, Monzó E, Tubbs S, Server A, Bigeleisen P. A novel marker for studying nerves. Clin Anat 2018; In Press. doi:10.1002/ca.23253

  4. Reina MA, Machés F, De Diego-Isasa P, Del Olmo C. Ultrastructure of endoneurium, Atlas of Functional Anatomy of Regional Anesthesia and Pain Medicine. Edited by Reina MA. New York, Springer, 2015, pp 37–58.

  5. Reina MA, Sala Blanch X, Arriazu R, Machés F. Microscopic morphology and ultrastructure of human peripheral nerves, Nerves and Nerve Injuries, Vol. 1: History, Embryology, Anatomy, Imaging, and Diagnostics. Edited by Tubbs RS, Rizk E, Shoja M, Loukas M. Cambridge, MA, Elsevier, 2015, pp. 91–106.

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