Summary
Nerve fiber injury and endoneurial edema were induced by the injection of the local anesthetic 2-chloroprocaine, tetracaine, procaine, etidocaine or mepivacaine into the soft tissue and fascia surrounding the sciatic nerve of Sprague-Dawley rats. Light microscopy demonstrated that the perineurial barrier was not mechanically damaged by the surgical procedure but, at 48 h post-injection, perineurial permeability was increased. Previous observations of leakage of horseradish peroxidase and the present report of neutrophils and eosinophils in the endoneurium indicate a disruption of blood-nerve barrier systems. Endoneurial edema was observed in the subperineurial, interstitial and perivascular regions. Axonal degeneration and demyelination occurred; the latter associated with accumulation of large lipid droplets in Schwann cells. Degranulation of mast cells, proliferation of fibroblasts and macrophage activity were noteworthy in affected areas. The findings are remarkable in that this is the first model of endoneurial edema by a neurotoxin which penetrates the perineurium, disrupting barrier system and inducing nerve fiber injury.
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References
Barsa J, Batra M, Fink BR, Sumi SM (1982) A comparative in vivo study of local neurotoxicity of lidocaine, bupivacaine, 2-chloroprocaine, and a mixture of 2-chloroprocaine and bupivacaine. Anesth Analg 61:961–967
de la Motte DJ, Hall SM, Allt G (1975) A study of the perineurium in peripheral nerve pathology. Acta Neuropathol (Berl) 33:257–270
Dyck PJ, Lais AC, Hansen A, Sparks MF, Low PA Parathasarthy S, Baumann WJ (1982) Technique assessment of demyelination from endoneurial injection. Exp Neurol 77:359–377
Fawcett DW (1966) An atlas of fine structure — the cell, 1st edn. Saunders, Philadelphia, pp 307–318
Gentili F, Hudson AR, Hunter D (1980) Clinical and experimental aspects of injection injuries of peripheral nerves. Can J Neurol Sci 7:143–151
Gentili F, Hudson AR, Hunter D, Kline DG (1980) Nerve injection injury with local anesthetic agents: a light and electron microscopic, fluorescent microscopic and horseradish peroxidase study. Neurosurgery 6:263–272
Gissen AJ, Datta S, Lambert D (1984) The chloroprocaine controversy II. Is chloroprocaine neurotoxic? Reg Anesth 9:135–145
Kalichman MW, Powell HC, Reisner LS, Myers RR (1986) The role of 2-chloroprocaine and sodium bisulfite in rat sciatic nerve edema. J Neuropathol Exp Neurol 45: 566–575
Lange W, Schropp A (1985) The morphology of lipopigment granules in oligodendrocytes of the cerebellum and spinal cord and in Schwann cells of the N ischiadicus of the cat, Japanese Waltzing mouse, and albino mouse. Acta Neuropathol (Berl) 65:330–334
Li DR, Bahar M, Cole G, Rosen M (1985) Neurological toxicity of the subarachnoid infusion of bupivacaine, lignocaine or 2-chloroprocaine in the rat. Br J Anaesth 57:424–429
Moore DC, Spierdijk J, vanKleef JD, Coleman RL, Love GF (1982) Chloroprocaine toxicity: four additional cases. Anesth Analg 61:155–159
Myers RR, Kalichman MW, Reisner LS, Powell HC (1986) Neurotoxicity of local anesthetics: altered perineurial permeability, edema and nerve fiber injury. Anesthesiology 64:29–35
Pizzolato P, Renegar OJ (1959) Histopathologic effects of long exposure to local anesthetics on peripheral nerves. Anesth Analg 38:138–141
Powell HC, Myers RR, Lampert PW (1980) Edema in neurotoxic injury. In: Spencer PS, Schaumburg HH (eds) Experimental and clinical neurotoxicology. Williams & Wilkins, Baltimore, pp 118–138
Powell HC, Knobler RL, Myers RR (1983) Peripheral neuropathy in the twitcher mutant. A new model of endoneurial edema. Lab Invest 49:19–25
Ravindran RS, Bond VK, Tasch MD, Gupta CD, Luerssen TG (1980) Prolonged neural blockade following regional anesthesia with 2-chloroprocaine. Anesth Analg 59:447–451
Ready LB, Plumer MH, Haschke RH, Austin E, Sumi SM (1985) Neurotoxicity of intrathecal local anesthetics in rabbits. Anesthesiology 63:364–370
Rechnagel RD (1983) A new direction in the study of the carbon tetra-chloride hepatotoxicity. Life Sci 33:401–408
Reisner LS, Hochman BN, Plumer MH (1980) Persistent neurologic deficit and adhesive arachnoiditis following intrathecal 2-chloroprocaine injection. Anesth Analg 59:452–454
Rosen MA, Baysinger CI, Shnider SM, Dailey PA, Norton M, Curtis JD, Collins M, Davis RL (1983) Evaluation of neurotoxicity after subarachnoid injection of large volumes of local anesthetic solutions. Anesth Analg, 62:802–808
Selander D, Dhuner KG, Lundborg G (1977) Peripheral nerve injury due to injection needles used for regional anesthesia: an experimental study of the acute effects of needle point trauma. Acta Anaesthesiol Scan 21:182–188
Selander D, Brattsand R, Lundborg R, Nordborg C, Olsson Y (1979) Local anesthetics: importance of mode of application, concentration and adrenaline for the appearance of nerve lesions. Acta Anaesthesiol Scand 23:127–136
Wang BC, Hillman DE, Spielholz NI, Turndorf H (1984) Chronic neurological deficits and Nesacaine-CE—an effect of the anesthetic, 2-chloroprocaine, or the antioxidant, sodium bisulfite? Anesth Analg 63:445–447
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Supported in part by USPHS NS18715, NS14162 and NS07078 and the Veteran's Administration Research Service
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Kalichman, M.W., Powell, H.C. & Myers, R.R. Pathology of local anesthetic-induced nerve injury. Acta Neuropathol 75, 583–589 (1988). https://doi.org/10.1007/BF00686203
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DOI: https://doi.org/10.1007/BF00686203