Abstract
Helical electrodes were implanted around the left and right common peroneal nerves of cats. Three weeks after implantation one nerve was stimulated for 4–16 hours using charge-balanced, biphasic, constant current pulses. Compound action potentials (CAP) evoked by the stimulus were recorded from over the cauda equina before, during and after the stimulation. Light and electron microscopy evaluations were conducted at various times following the stimulation. The mere presence of the electrode invariably resulted in thickened epineurium and in some cases increased peripheral endoneurial connective tissue beneath the electrodes. Physiologic changes during stimulation included elevation of the electrical threshold of the large axons in the nerve. This was reversed within one week after stimulation at a frequency of 20 Hz, but often was not reversed following stimulation at 50–100 Hz. Continuous stimulation at 50 Hz for 8–16 hours at 400 μA or more resulted in neural damage characterized by endoneurial edema beginning within 48 hours after stimulation, and early axonal degeneration (EAD) of the large myelinated fibers, beginning by 1 week after stimulation. Neural damage due to electrical stimulation was decreased or abolished by reduction of the duration of stimulation, by stimulating at 20 Hz (vs. 50 Hz) or by use of an intermittent duty cycle. These results demonstrate that axons in peripheral nerves can be irreversely damaged by 8–16 hours of continuous stimulation at 50 Hz. However, the extent to which these axons may subsequently regenerate is uncertain. Therefore, protocols for functional electrical stimulation in human patients probably should be evaluated individually in animal studies.
Similar content being viewed by others
References
Adams, W. E., The blood supply of nerves. II. The effects of exclusion of its regional sources of supply on the sciatic nerve of the rabbit. J. Anat. 77:243–250; 1942.
Agnew, W.F.; McCreery, D.B.; Yuen, T.G.H.; Bullara, L.A.. Electrical stimulation of peripheral nerve (Abstr) Proceed. IEEE/Ninth Annual Conf. Engnr. Med. and Biol. Soc. 3:1563–1564; 1987.
Asbury, A.K. Renaut bodies. A forgotten endoneurial structure. J. Neuropath. Exp. Neurol. 22:334–343; 1973.
Bell, M.A.; Weddell, A.G.M. A descriptive study of the blood vessels of the sciatic nerve in the rat, man and other mammals. Brain 107:871–898; 1984.
Beuch, W.; Friede, R.L. Remodeling of nerve structure in experimental isoniazid neuropathy in the rat. Brain 109:759–769; 1986.
Boyd, I.A.; Kalu, K.U. Scaling factor relating conduction velocity and diameter for myelinated afferent fibers in the cat hind limb. J. Physiol. 289:277–297; 1978.
Brindley, G.S.; Polkey, C.E.; Rushton, D.N. Sacral anterior root stimulators for bladder control in paraplegia. Paraplegia 20:365–381; 1982.
Brummer, S.B.; Turner, M.J. Electrochemical considerations for safe stimulation of the nervous system. IEEE Trans. Biomed. Eng. BME 24:59–63; 1977.
Burton, C. Implanted devices for electronic augmentation of nervous system function. Med. Instrum. 9:221–233; 1975.
Davis, L.A.; Gordon, T.; Hoffer, J.A.; Jhamaudas, J.; Stein, R.B. Compound action potentials recorded from mammalian peripheral nerves following ligation or resuturing. J. Physiol (Lows)285:543–559; 1978.
Dyck, P.J.; Karnes, J.; Lais, A.; Lofgrew, E.P.; Stevens, J.C. Pathologic alterations of the peripheral nervous system of humans In: Dyck, P.J.; Thomas, P.K.; Lambert, E.H.; Bringe, R., eds.Peripheral Neuropathy. Philadelphia: W.B. Saunders; 1984: pp. 760–870.
Eisenberg, B.R.; Brown, J.M.; Salmons, S. Restoration of fast muscle characteristics following cessation of chronic stimulation. The ultrastructure of slow-to-fast transformation. Cell Tis. Res. 238:221–230; 1984.
Gillespie, M.J.; Stein, R.B. The relationship between axon diameter, myelin thickness and conduction velocity during atrophy of mammalian peripheral nerves. Brain Res. 259:41–56; 1983.
Glenn, W.W.L.; Holcomb, W.G.; Hogan, J.F.; Kaneyuki, T.; Kim, J. Long-term stimulation of the phrenic nerve for diaphragm pacing. In: Hambrecht, F.T.; Reswick, J.B., eds. Functional Electrical Stimulation: Applications in Neural Prostheses. New York: Marcel Dekker, Inc.; 1977: pp. 97–112.
Glenn, W.W.L.; Phelps, M.L. Diaphragm pacing by electrical stimulation of the phrenic nerve. Neurosurg. 17:974–984; 1985.
Gorman, P.H.; Mortimer, J.T. The effect of stimulus parameters on the recruitment characteristics of direct nerve stimulation. IEEE Trans. Biomed. Eng. BME 30:407–414; 1983.
Hershberg, P.I.; Sohn, D.; Agrawal, G.P.; Kantrowitz, A. Histologic changes in continuous, longterm electrical stimulation of a peripheral nerve. IEEE Trans. Biomed. Eng. 14:109–114; 1967.
Hiscoe, H.B. Distribution of nodes and incisures in normal and regenerated nerve fibers. Anat. Rec. 99:447–475; 1947.
Jacobs, J.; LeQuesne, P.M. Toxic disorders of the nervous system. In: Adams, J.H.; Corsellis, J.A.N.; Duchen, L.W., eds. Greenfield Neuropathology. New York: John Wiley & Sons, 4th Ed.; 1984: pp. 627–698.
Kim, J.H.; Manuelidis, E.E.; Glenn, W.W.; Fukuda, Y.; Cole, D.S.; Hogan, J.F. Light and electron microscopic studies of phrenic nerves after long-term electrical stimulation. J. Neurosurg. 58:84–91; 1983.
Kim, J.H.; Manuelidis, E.E.; Glenn, W.W.; Kaneyuki, T. Diaphragm pacing — Histopathological changes in the phrenic nerve following long-term electrical stimulation. J. Thor. Cardiovasc. Surg. 72:602–608; 1976.
Kiwerski, J.; Weiss, M.; Pasniczek, R. Electro-stimulation of the median nerve in tetraplegics by means of implanted stimulators. Paraplegia 21:322–326; 1983.
MacKinnon, S.E.; Dellon, A.L.; Hudson, A.R.; Hunter, D.A. Chronic nerve compression—an experimental model in the rat. Annals. Plast. Surg. 13:112–120; 1984.
McNeal, D.R.; Waters, R.; Reswick, J. Experience with implanted electrodes at Rancho Los Amigos Hospital. Neurosurg. 2:228–229; 1977.
Makitie, J.; Teravainen, H. Peripheral nerve injury and recovery after temporary ischemia. Acta. Neuropath. 37:55–63; 1977.
Meier, C.; Sollman, H. Regeneration of cauda equina fibers after transection and end-to-end suture. J. Neurol. 215:81–90; 1977.
Munsat, T.L.; McNeal, D.R.; Waters, R.L. Preliminary observations on prolonged stimulation of peripheral nerve in man. Excerpta. Medica. Intl. Congress, Series No. 360:42–50; 1974.
Nashold, B.S., Jr.; Goldner, J.L.; Mullen, J.B.; Bright, D.S. Long-term pain control by direct peripheral nerve stimulation. J. Bone and Joint Surg. 64-A:1–10; 1982.
Picaza, J.A.; Hunter, S.E.; Cannon, B.W. Pain suppression by peripheral nerve stimulation. Appl. Neurophysiol. 40:223–234; 1977/78.
Rydevik, B.; Brown, M.D.; Lundborg, G. Pathoanatomy and pathophysiology of nerve root compression. Spine 9:1–15; 1984.
Schmidt, R.A.; Bruschini, H.; Van Gool, J.; Tanagho, E.A. Mieturition and the male genitourinary response to sacral root stimulation. Invest. Urol. 17:125–130; 1979.
Shelden, C.H.; Pudenz, R.H.; Doyle, J. Electrical control of facial pain. Amer. J. Surg. 114:209–212; 1967.
Strojnik, P.; Acimovic, R.; Vavken, E.; Simic, V.; Stanic, U. Treatment of drop foot using an implantable peroneal underknee stimulator. Scand. J. Rehab.Med. 19:37–43; 1987.
Sweet, W.H. Control of pain by direct electrical stimulation of peripheral nerves. Clin. Neurosurg. 23:103–111; 1976.
Talonen, P.; Baer, G.; Hakkinen, V.; Markkula, H. Implanted phrenic nerve stimulations in 3 tetraplegic patients. Life Support Systems 2: Supplement 1; 1984.
Thuroff, J.W.; Bazeed, M.A.; Schmidt, R.A.; Wiggin, D.M.; Tanagho, E.A. Functional pattern of sacral root stimulation in dog micturition. J. Urol. 127:1031–1033; 1982.
Villiers, de, R; Nose, Y.; Meier, W.; Kantrowitz, A. Long term, continuing electrostimulation of a peripheral nerve. Trans. Am. Soc. Artif. Internal Organs 10:357–365; 1964.
Waters, R.L.; McNeal, D.R.; Faloon, W.; Clifford, B. Functional electrical stimulation of the peroneal nerve for hemiplegia—Long-term clinical follow-up. J. Bone Joint Surg. 67-A:792–793; 1985.
Waters, R.L.; McNeal, D.; Perry, J. Experimental correction of footdrop by electrical stimulation of the peroneal nerve. J. Bone Joint Surg. Ser. A 57:1047–1054; 1975.
Yuen, T.G.H.; Agnew, W.F.; Bullara, L.A. Histopathological evaluation of dog sacral nerve following chronic electromicturition. Neurosurg. 14:449–455; 1984.
Zilvold, G.; Hermens, H. J.; Kreuwel, H.; de Waal, C.; Alste, J. V. Experiences with an implantable nervus femoralis stimulator. Proceed. Eighth Intern. Symp. on ECHE, Dubrovnik, 1984.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Agnew, W.F., McCreery, D.B., Yuen, T.G.H. et al. Histologic and physiologic evaluation of electrically stimulated peripheral nerve: Considerations for the selection of parameters. Ann Biomed Eng 17, 39–60 (1989). https://doi.org/10.1007/BF02364272
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02364272