Unmyelinated fibers in the trigeminal motor root. Possible relationship to the results of trigeminal rhizotomy

Transcription

1 J Neurosurg 49: , 1978 Unmyelinated fibers in the trigeminal motor root Possible relationship to the results of trigeminal rhizotomy RONALD F. YOUNG, M.D. Division of Neurosurgery, University of California at Los Angeles School of Medicine and Harbor General Hospital, Torrance, California ~," Spinal ventral roots have been shown by electron microscopy to contain a substantial number of unmyelinated fibers. Physiological studies have confirmed that many of these subserve a sensory function. In this investigation the fiber spectrum of the human trigeminal motor root was studied by electron microscopy and it was determined that up to 20% of fibers were unmyelinated. This accounted for approximately 300 to 1000 fibers per root. Since visceral efferent fibers are thought not to occur in the trigeminal root, it appears likely that these unmyelinated fibers may be afferent in nature. It is believed that the presence of a substantial number of unmyelinated fibers in the trigeminal motor root may account for residual sensation or failure of pain relief after rhizotomy of the trigeminal portio major root. KEY WORDS ~ trigeminal nerve 9 trigeminal motor root 9 trigeminal rhizotomy 9 facial pain T he generally accepted "law of Bell and Magendie" stated that spinal dorsal roots were sensory in function, and ventral roots were motor in function?,e However, the idea that sensation may reach the spinal cord via ventral roots was stated as early as 1911.~3 The identification of afferent myelinated fibers in ventral roots, with peripheral cutaneous receptive fields, gave some support to the latter view, ~~176 but these fibers seemed too few in number to account for residual sensation or failure of pain relief after dorsal rhizotomy. Electron microscopy allowed the demonstration of a significant number of unmyelinated fibers in the ventral roots of the frog, ~2,~5 cat/4,8., and human?,~3 In man, 13% to 51% of fibers in the ventral roots are unmyelinated, and a significant number of unmyelinated fibers were found in every ventral root from C1-$4 inclusive? a3 Clifton, et al./.4 and Coggeshall and Ito 7 confirmed that many of these unmyelinated fibers were associated with peripheral receptive fields in both cutaneous and visceral locations. Considerable evidence therefore exists that ventral spinal roots may possess a significant sensory function. Traditional neuroanatomical concepts consider the trigeminal portio major root to be analogous to spinal dorsal roots and to be sensory in function. The portio minor is considered analogous to spinal ventral roots and 538 J. Neurosurg. / Volume 49 / October, 1978

2 Unmyelinated fibers in trigeminal motor root is thought to be purely motor in function. The present study was undertaken in light of the recent anatomical and physiological studies of unmyelinated fibers in spinal ventral roots and in view of the clinical suspicion 1'"'15 that the trigeminal motor root might subserve a sensory function. The purpose of the study was to evaluate the fiber composition of the trigeminal motor root by electron microscopy to determine the potential contribution of unmyelinated fibers. Materials and Methods Five human trigeminal motor roots were studied. The Gasserian ganglion and attached trigeminal motor and sensory roots were obtained post mortem. The trigeminal motor root was isolated from this block with the aid of a dissecting microscope. The root was immersed in cold 3% glutaraldehyde in 0.1 M cacodylate buffer for up to 3 days. Subsequently it was washed in buffer and post-fixed for 2 to 3 hours in 1% osmium tetroxide in cacodylate buffer. The tissue was then dehydrated and embedded in Maraglas. Thick sections were cut and examined under light microscopy to obtain the total count of myelinated fibers for each root. Ultra-thin sections were cut on a Porter-Blum MT-2B ultramicrotome* and stained with 0.5% uranyl acetate and lead citrate for electron microscopy. For fiber spectrum analysis random areas from the cross-section of each nerve were photographed on a Siemans Elmiskop 101 transmission electron microscopet and composite photomontages were constructed, each covering an area of approximately 2000 sq #. The myelinated and unmyelinated fibers were subsequently counted from these montages using methods previously reported.28 A computerized digitizer was used to obtain the diameter of each fiber. These data were stored in an SEL 800 computer and fiber-size histograms were constructed by computer and printed for each root. *Porter-Blum MT-2B ultramicrotome manufactured by the Dupont Co., Instrument Products, Biomedical Division, Newtown, Connecticut. tsiemans Elmiskop 101 transmission electron microscope manufactured by Siemans Corporation, Berlin, Germany. TABLE 1 Human trigeminal motor root* Total Calculated Root Myelinated % Total No. Fiber Count Unmyelinated Unmyelinated (LM) (EM) Fibers *LM = light microscopy; EM = electron microscopy. Results Unmyelinated fibers were identified in considerable numbers in the human trigeminal motor root. Their morphology is similar to that seen with unmyelinated fibers in the trigeminal sensory root, 28 spinal dorsal roots, TM and spinal ventral roots 5,28 (Figs. 1 and 2). The fibers are enclosed within infoldings of Schwann cell membranes and form small Remak bundles. Although occasional bundles contained up to four or six unmyelinated fibers, most contained only one or two. Thus, in general, the bundles are smaller than those seen in the trigeminal sensory root or in spinal dorsal or ventral roots. Table 1 illustrates the fiber counts obtained, and shows that 12% to 20% of the total fibers in the motor root are unmyelinated. Based on the counts of total myelinated fibers obtained by light microscopy and the percentage of unmyelinated fibers, we calculated that approximately 300 to 1000 unmyelinated fibers occur in each human trigeminal motor root. Figure 3 illustrates the fiber size spectrum of a single human trigeminal motor root. Essentially all fibers in the size range of 0 to 2/~ represent unmyelinated fibers. Individual study of the unmyelinated fibers alone revealed that the majority ranged from 0.3 to 0.5 # in size. Figure 3 illustrates a major grouping of myelinated fibers between 5 and 11 /z, probably representing mainly alpha motor neuron axons. A much smaller peak is noted at 2 to 3 u and may represent mainly gamma motor neuron axons. J. Neurosurg. / Volume 49 / October,

3 R. F. Young FIG. 1. Single unmyelinated fiber occurring in the human trigeminal motor root (arrow). The Schwann cell nucleus (N) and the mesaxonal infolding of its cytoplasmic membrane around the unmyelinated fiber are evident. Bar represents 1 ~t. Discussion In 1926, Windle, 28 using the light microscope, found that about 5% of the fibers in the cat trigeminal motor nerve were unmyelinated. That study was hampered by the relatively low resolution of the light microscope in the size range of unmyelinated fibers. Little further attention was paid to the fiber composition of the trigeminal motor nerve or root. The present study represents the first ultrastructural analysis of the fiber composition of the human trigeminal motor root. The study indicates that a considerable proportion, up to 20%, of fibers in the human trigeminal motor root are unmyelinated. While this number is substantial, it represents a smaller proportion than that identified in human ventral roots. 5,28 The latter have been shown to contain 12% to 51% unmyelinated fibers. That some of the unmyelinated fibers, at least in certain ventral roots, are visceral efferents has been determined in cats by ventral root section. Such studies 4 suggest that about half of the unmyelinated fibers in the S-3 and S-4 ventral roots of the cat are visceral efferents. If one subtracts these fibers, then about 20% of the total fiber count of the S-3 and S-4 ventral roots are potentially sensory in function. This figure is similar to that reported in the present study. It appears unlikely that any of the unmyelinated fibers we have identified in the trigeminal motor root are visceral efferents. Cranial visceral efferent preganglionic parasympathetic fibers are usually considered to be confined to the third, seventh, ninth, and tenth cranial nerves. Thus it appears likely that the unmyelinated fibers we have iden- 540 J. Neurosurg. / Volume 49 / October, 1978

4 Unmyelinated fibers in trigeminal motor root FIG. 2. A group of five unmyelinated fibers in the human trigeminal motor root (arrows). Schwann cell nuclei are not present in this section, but the Schwann cell cytoplasmic membrane and the contained cytoplasm are shown. Bar represents 1 /~. Unmyelinated fibers range from 0.2 to 1.5 u in diameter. tiffed may be afferent in nature. In addition, while the percentage of fibers is relatively small, on an absolute basis 300 to 1000 fibers per trigeminal motor root are unmyelinated. This is a substantial number of fibers and could easily account for a significant functional role. Unmyelinated fibers in spinal ventral roots with a sensory function were thought to originate primarily from dorsal root ganglion cells. ~ In a recent study, Yamamoto, et al.? 7 using horseradish peroxidase tracing, identified a substantial number of ganglion cells within the ventral root substance itself, as well as in peripheral nerves and the spinal cord. Unmyelinated fibers in the trigeminal motor root probably originate in sensory ganglion cells in the Gasserian ganglion. The most likely routes of travel between sensory FIG. 3. Fiber-size histogram of one human trigeminal motor root. Unmyelinated fibers (diameters 0 to 2 u) represent a substantial proportion of the total fiber population. J. Neurosurg. / Volume 49 / October, ,41

5 and motor root are the so-called intermediate trigeminal or accessory trigeminal fibers. These were first described by Dandy, 8,~4 and later studied by Jannetta and Rand 16,~7 and Gudmundsson, et al. x4 These fibers vary from one or two up to eight to 10 or more per root, and were identified in 47 of 50 human roots studied by Gudmundsson, et al. ~4 The fibers anastomose between the motor and sensory roots extending both proximally and distally from various portions of both roots. Detailed anatomical and physiological studies of these fibers have not been carried out so that their histological composition and function are unknown. Considerable speculation about their function has arisen, however, primarily from the results of trigeminal rhizotomy. Some authors suggested a potential motor function of these intermediate fibers 2~ but most investigators have felt them to be sensory in function. Dandy s'24 attributed preservation of sensation after posterior fossa trigeminal rhizotomy to sparing of the accessory fibers, which he felt were sensory in function. Jannetta and Rand ~6'~7 also suggested that, if the intermediate fibers were preserved after trigeminal root section, light touch sensation was preserved on the face. Sir Victor Horsley was probably the first to suggest that sensory fibers were present within the trigeminal motor root. 15 Adson 1 indicated that if trigeminal neuralgia persisted after apparently complete trigeminal rhizotomy the motor root should be sectioned since it could contain sensory fibers. Gudmundsson, et al., a" also suggested consideration of motor-root section if painful tic recurred after complete section of the sensory root. While these suggestions are consistent with the finding of a considerable number of unmyelinated fibers in the trigeminal motor root, they certainly do not confirm the sensory function of such fibers. Denny-Brown and Yanagisawa ~ suggested that residual sensation and persistent pain perception after trigeminal rhizotomy arises from overlapping cutaneous sensory input to the spinal trigeminal nucleus by way of the seventh and tenth cranial nerves and the cervical nerve roots at C1-4. Such an explanation does not require the presence of sensory fibers in the motor root. Peripheral receptive fields have been determined for at least some unmyelinated fi- R. F. Young bers 3'4,7 and for a few myelinated fibers 7,1~176 in spinal ventral roots. The afferent nature of some of the ventral root fibers is thus firmly established. No such definite physiological confirmation of the sensory function of fibers in the trigeminal motor root exists. The clinical suggestions of Horsley, et al., 15 Dandy, TM Adson, 1 and Jannetta and Rand, ae,~7 and the anatomical studies of the intermediate trigeminal fibers ~4,:~,~7 are interesting in view of the findings reported here. The presence of a substantial number of unmyelinated fibers in the human trigeminal motor root has been clearly demonstrated. Only further anatomical study of the intermediate trigeminal fibers and physiological study of trigeminal motor root fibers can establish the source and function of these unmyelinated fibers. The possibility that they relate to the preservation of sensation and persistence of pathological facial pain after trigeminal sensory rhizotomy is intriguing. Acknowledgments The author wishes to express his appreciation to Richard Stevens and Norma Horton for technical assistance and to Donna Fabrizio for preparation of the manuscript. References 1. Adson AW: Unpublished data cited by Baker GS: Personal communication, 1969: Cited in Reference Applebaum ML, Clifton GL, Coggeshall RE, et al: Unmyelinated fibres in the sacral 3 and caudal 1 ventral roots of the cat. J Physiol 256: , Clifton GL, Coggeshall RE, Vance WH, et al: Receptive fields of unmyelinated ventral root afferent fibres in the cat. J Physiol 256: , Clifton GL, Vance WH, Applebaum ML, et al: Responses of unmyelinated afferents in the mammalian ventral root. Brain Res 82: , Coggeshall RE, Applebaum ML, Fazen M, et al: Unmyelinated axons in human ventral roots, a possible explanation for the failure of dorsal rhizotomy to relieve pain. Brain 98: , Coggeshall RE, Coulter JD, Willis WD Jr: Unmyelinated axons in the ventral roots of the cat lumbosacral enlargement. J Comp Neurol 153:39-58, J. Neurosurg. / Volume 49 / October, 1978

6 Unmyelinated fibers in trigeminal motor root 7. Coggeshall RE, Ito H: Sensory fibres in ventral roots L7 and S1 in the cat. J Physiol 267: ; Dandy WF: An operation for the cure of tic douloureux: partial section of the sensory root at the pons. Arch Surg 18: , Denny-Brown D, Yanagisawa N: The function of the descending root of the fifth nerve. Brain 96: , Dimsdale JA, Kemp JM: Afferent fibres in the ventral nerve roots in the rat. J Physiol 187:25p-26p, 1966 (Proceedings) 11. Emery DG, Ito H, Coggeshall RG: Unmyelinated axons in thoracic ventral roots of the cat. J Comp Neurol 172:37-48, Gamble H J, Eames RE: Electron microscopy of human spinal nerve roots. Arch Neurol 14:50-53, Groves EWH: On the division of the posterior spinal nerve roots: (I) for pain, (II) for visceral crises, (III) for spasm. Lancet 2:79-85, Gudmundsson K, Rhoton AL Jr, Rushton JG: Detailed anatomy of the intracranial portion of the trigeminal nerve. J Neurosurg 35: , Horsley V, Taylor J, Colman WS: Remarks on the various surgical procedures devised for the relief or cure of trigeminal neuralgia (tic douloureux). Br Med J 2: , , , Jannetta P J, Rand RW: Microanatomy of the trigeminal nerve. Anat Rec 154:362, 1966 (Abstract) 17. Jannetta P J, Rand RW: Transtentorial retrogasserian rhizotomy in trigeminal neuralgia, in Rand RW (ed): Mierosurgery. St. Louis: CV Mosby, 1969, pp Kato M, Hirata Y: Sensory neurons in the spinal ventral roots of the cat. Brain Res 7: , Kato M, Tanj I: Physiological properties of sensory fibers in the spinal ventral roots in the cat. Jpn J Physiol 21:71-77, Ryall RW, Piercey MF: Visceral afferent and efferent fibers in sacral ventral roots in cats. Brain Res 23:57-65, Saunders R, Sachs E: Accessory fibers of the fifth nerve. Presented at the meeting of the American Association of Neurological Surgeons, Washington, DC, Sutherland RM, Nunnemacher RE: Fibers in ventral spinal nerves of the frog. J Comp Neurol 156:39-48, Sykes MT, Coggeshall RE: Unmyelinated fibers in the human L, and L5 ventral roots. Brain Res 63: , Troland CE, Ostenasek F J: Selected Writings of Walter E. Dandy. Springfield, I11: Charles C Thomas, 1957, pp Vance WH, Clifton GL, Applebaum ML, et al: Unmyelinated preganglionic fibers in frog ventral roots. J Comp Neurnl 164: , Windle WF: The distribution and probable significance of the unmyelinated nerve fibers in the trigeminal nerve of the cat. J Comp Neurol 41: , Yamamoto T, Takahashi K, Satomi H, et al: Origins of primary afferent fibers in the spinal ventral roots in the cat as demonstrated by the horseradish peroxidase method. Brain Res 126: , Young RF, King RB: Fiber spectrum of the trigeminal sensory root of the baboon determined by electron microscopy. J Neurosurg 38:65-72, 1973 This investigation was supported by Grant DE from the National Institutes of Health, National Institute of Dental Research. Address reprint requests to: Ronald F. Young, M.D., Harbor General Hospital, Box 173, 1000 West Carson Street, Torrance, California J. Neurosurg. / Volume 49 / October,