EXPERIMENTAL

NEUROLOGY

115,60-64

(1992)

Response of the Gustatory System to Peripheral Nerve Injury MICHAEL Department

of BioStructure

and Function,

School

A. BARRY

of Dental

Medicine,

AND MARION University

The vertebrate gustatory system has features that should facilitate recovery from peripheral nerve damage. There is normally turnover of taste bud (TB) cells, which requires afferent taste nerve endings to constantly reform synaptic endings with appropriate young receptor cells. Correspondingly, many factors important in development and regeneration, such as the neural cell adhesion molecule (lo), are likely to be found in normal TB cells. In addition taste fibers regenerate easily in adult mammals. For example, in hamsters, severed gustatory fibers will cross gaps of 5 mm or more (unpublished observations). There are important differences in response properties, morphology, and immunohistochemistry among TB fields. In mammals, TBs located on the anterior tongue (fungiform papillae) and soft palate are innervated by the VIIth nerve: chorda tympani (CT) and greater superficial petrosal (GSP) branches, respectively. These TB fields appear to be most concerned with appetitive stimuli (24). The TB fields in the poste-

RESPONSE

Farmington,

Connecticut

06030

CONSIDERATIONS

TO PERIPHERAL NERVE AND REGENERATION

DAMAGE

Taste buds. TBs are thought to be a classic example of neurotrophically dependent receptor cells. Denervation causes a rapid loss of cells (11). The effect of denervation can be duplicated by blocking axonal transport, suggesting that a trophic chemical is secreted (31). Following denervation, TBs have been thought to “disappear”; however, some TB cells persist (38). Adult nerves do not induce TBs de nouo (20), although following reinnervation of the epithelium, TBs with a full complement of cell types form within 2 days (8). This implies that stem cells that can rapidly proliferate to form TBs are present before reinnervation. Stem cells may lie dormant outside TBs (18) or persist as TB remnants. Denervated TBs persist in some fish (37) and amphibian preparations (35), but not in mammalian vallate or foliate papillae (11, 31). However, denervated rodent 60

Inc. reserved.

Center,

The CT is the most vulnerable taste nerve. In humans, the CT can be damaged surgically (6,9,13,39) or pathologically (1, 6, 26). Following CT section taste function does not recover (9, 39), but anastomosis has not been attempted. If the CT nerve is stretched or crushed during surgery, taste acuity usually gradually recovers (6,9,39). Subjective impairment is greater for section than partial damage of the CT, especially following bilateral surgery (6, 39). The combined CT-L nerve can be damaged during third molar extractions (5), and recovery of trigeminal function may be facilitated by additional surgery (29). It has been suggested that recovery of taste function is less likely (17), because of intermingling of CT and L fibers within the combined nerve (12).

INTRODUCT’ION

$3.00 0 1992 by Academic Press, of reproduction in any form

Health

CLINICAL

Inc.

0014-4886/92 Copyright All rights

of Connecticut

rior oral cavity (including foliate and vallate papillae) innervated by the glossopharyngeal nerve (IX) have a greater role in responding to aversive stimuli (36). Somatosensory innervation, from the IXth nerve in the posterior and from the lingual (L) branch of the trigeminal nerve in the anterior oral cavity, occurs around but not on TB cells (22).

Peripheral taste nerve damage occurs as a result of disease and surgery. The response depends on the taste field affected and the species. Nerve regeneration is robust after the nerve is crushed or after it is cut if the severed ends are anastomosed. Taste buds, which appear after nerve regeneration, may be derived from dormant stem cells outside of taste buds or from remnants of taste buds that persist following denervation. Sprouting by intact taste nerves into denervated fields apparently does not occur. Regenerated primary afferents have taste response specificity, but it is unknown if neural response types are retained peripherally or centrally. Recent behavioral studies show specific deficits following loss of restricted taste fields in rodents, but little is known about recovery after nerve regeneration. Specific deficits have not been demonstrated in humans, although taste sensitivity has been correlated with numbers of taste buds. Enigmas such as these may be solved once the response of the central nervous syso 1992 Academic tem to gustatory nerve injury is defined. Press,

E. FRANK

GUSTATORY

NERVE

61

INJURY

1

Case

3

3

4

5

6

Case

FIG. 1. Quantification of number and size of fungiform taste buds (TBs) 21 days following unilateral CT-L nerve section in the golden hamster. The nerve was exposed behind the chin, a section of nerve removed, and the nerve devitalized. The tissue was stained histochemically for calcium-ATPase (see Fig. 2) and counterstained with a Nissl stain. Identification of TBs was based on staining and structure. All fungiform TBs in each of the six experimental animals were counted and measured. (a) Number of persisting fungiform TBs expressed as a percentage of the number on the normal side. Most TBs persist. (b) Mean size of calcium-ATPase-stained part of all TBs on normal and denervated side of tongue. The largest cross-sectional area was measured for each TB. Error bars indicate standard error of the mean. In each case TB sizes were significantly (P < 0.001) smaller on the denervated side (3).

fungiform TBs persist for months (16, 38). At 3 weeks following CT-L denervation, most hamster fungiform TBs remain (Fig. la) (3). The cells in these TBs continue to turnover (Oliver and Whitehead, personal communication). Furthermore, many denervated TB cells continue to express high levels of calcium-dependent ATPase, a characteristic of mature TB cells (Fig. 2) (3). We have utilized this stain to quantify the decrease in TB size following denervation (Fig. lb). Sprouting. There is no direct evidence that intact or regenerating gustatory nerve fibers sprout to innervate nearby denervated TBs (6, 7, 21, 23, 32) even within a single vallate (14) or foliate (41) papilla. Following unilateral CT cuts there is no sprouting from the contralatera1 CT (Fig. 3). Trigeminal fibers may sprout across the midline to innervate denervated contralateral fungiform papillae (23), but there is no evidence that intact or regenerated trigeminal afferents form synapses with TB cells (22, 32). Central nervous system anatomy. Little is known about anatomical responses of the central nervous system to peripheral nerve damage in adults. In developing rats (25), following receptor damage to the CT taste field, the central terminal field of the IXth nerve increases in size. Terminal fields of the CT and IX nerves

FIG. 2.

Photomicrograph of hamster fungiform papilla stained with calcium-dependent ATPase. Central mature TB cells but not the immature peripheral (im) TB cells stain intensely with calcium

ATPase. densely. sensory primarily

Nerve fibers and their Schwann cell sheaths also stain Fibers on the outer edge of the papilla are primarily somato(L). Fibers coursing through the middle of the papilla are gustatory (CT).

62

BARRY 4

3

2

AND

1

I

E r

-2057-i FIG. 3. Whole nerve recordings from experimental (E, upper traces) and control (C, lower traces) CT nerves in response to NaCl in golden hamster. Recordings were made 28 days after cutting and devitalizing the CT in the middle ear on the experimental side. Small pieces of filter paper soaked with 0.1 M NaCl were applied to the tongue at the sites shown on the tongue (sites l-4). Times of the application are indicated by the arrows (upper traces) and dots (lower traces). The experimental CT did not respond, thus no functional regeneration occurred. The control CT responded only to ipsilateral stimulation (sites 1, 2), indicating that sprouting of CT fibers across the midline does not occur (unpublished data from experiments described in abstract (21)).

in the solitary nucleus are characterized by relatively elevated levels of acetylcholinesterase (AChE) (2). Cutting or crushing these nerves in adult hamsters results in a dramatic reduction in AChE staining concomitant with the disappearance of foliate TBs (Fig. 4). Preliminary evidence indicates that normal expression of AChE does not return after 8 weeks, although most foliate TBs reappeared in 4-5 weeks following nerve damage. Possibly the induction and innervation of new TBs is not indicative of a fully functional system. Physiology. Whole nerve responses of the regenerated, crushed gerbil CT nerve recover by 3 days after reinnervation of the epithelium (7). Single CT units at 12 weeks following CT-L crush in cats had lower con-

FRANK

duction velocities and showed attenuated responses to a narrower range of stimuli (32). As in other sensory systems, regeneration after nerve section may be less successful than after crush (32), but if the severed ends are anastomosed, regeneration is successful (19, 31). There are no published studies on the physiological responses of the central nervous system to gustatory nerve injury. It is important to demonstrate whether neural response types are maintained following regeneration; if not, behavioral recovery is less likely. Behavior. Recent studies in rodents have found specific deficits in the discrimination of sodium salts following bilateral CT section (34, 40), and in responses to sweeteners following bilateral section of the CT (30) or the GSP and CT (24). Bilateral IXth nerve section results in dramatic deficits in rejection responses to bitter stimuli (36). Acute loss of CT input in humans results in an increase in contralateral sensitivity (4) similar to the ipsilateral effects described for the solitary nucleus of rats (15). Considering this finding and the frequent lack of perception of taste problems by people with nerve damage (4, 6, 39), it is surprising that relatively subtle individual or strain differences in TB numbers in humans and rodents correlate with sensitivities to taste stimuli (27, 28). Finally, preliminary evidence suggests that after CT regeneration in rats there is a return of sensitivity to sodium salts (33), which corresponds to partial recovery of taste seen in humans (see clinical considerations above). SUMMARY

There are many gaps in our knowledge of the effects of peripheral nerve damage on the gustatory system. Perceptual deficits are seen in laboratory animals, but have not been demonstrated in humans. Nerve regeneration is robust in laboratory animals, but factors critical for regeneration in humans are not established. Taste

FIG. 4. Photomicrograph of transverse brain section at the level of the rostra1 part solitary tract nucleus (NST) in a golden hamster sacrificed 2 weeks after the left CT nerve was cut in the middle ear. The section was stained histochemically to reveal acetylcholinesterase (AChE). The band of dense AChE staining in the NST (delimited by arrows on the right side) coincides with the terminal field of CT primary afferents (2). Following the CT nerve cut there is a dramatic decrease in the expression of AChE in the NST. Compare areas delimited by arrows on the left side. T, solitary tract.

GUSTATORY

NERVE

buds and physiological responses of peripheral nerves recover after nerve regeneration. However, little is known about the return of gustatory discrimination or about long-term effects on the central nervous system. ACKNOWLEDGMENTS This

work

was supported

by NIH

nerve 2.

3.

S. M. to middle

Grants

DC00168

and DC00853. 20.

1974. The vulnerability ear disease. J. Laryngol.

of the chorda tympani Otol. 88: 457-466.

BARRY, M. A., C. B. HALSELL, AND M. C. WHITEHEAD. 1991. Organization of the nucleus of the solitary tract in the hamster: Acetylcholinesterase, NADH dehydrogenase and cytochrome oxidase histochemistry. J. Electron Microsc. Tech., in press. BARRY, M. A., AND L. D. QAVOY. 1990. Elevated calcium dependent ATPase activity of plasma membranes of normal and denervated fungiform taste bud cells. Chem. Senses 15: 550.

4.

BARTOSHUK, Bull. Psychon.

5.

BLACKBURN, C. W., AND P. A. BRAMLEY. 1989. Lingual nerve damage associated with the removal of lower third molars. Br. Dent. J. 167: 103-107.

6.

BULL, T. R. 1965. Taste and the chorda 0tol. 79: 479-493. CHEAL, M., W. P. DICKEY, L. B. JONES, Taste fiber responses during reinnervation lae. J. Comp. Neurol. 172: 627-646.

7.

L. M. 1991. Sensory Sot. 23: 250-255.

18 . 19.

REFERENCES 1. ARNOLD,

17.

factors

in eating

21.

22.

23.

behavior. 24.

tympani.

J. Laryngol.

AND B. OAKLEY. of fungiform

25.

1977. papil-

8. CHEAL,

26.

9.

27.

10.

M., AND B. OAKLEY. 1977. Regeneration of fungiform taste buds: Temporal and spatial characteristics. J. Camp. Neurol. 172:609-626. CHILLA, R., J. NICKLATSCH, AND C. ARGLEBE. 1982. Late sequelae of iatrogenic damage to chorda tympani nerve. Actu Otoluryngol. (S~ochho~rn~ 94: 461-465. FINGER, T. E., H. SRIDHAR, M. WOMBLE, V. L. ST. JEOR, AND J. C. KINNAMON. 1987. Kmmunoreactivity to neuronal growthdependent membrane glycoprotein occurs in a subset of taste receptor cells in rat taste buds. Ann. N. Y. Acad. Sci. 510: 284-

11.

12.

~JI~OTO, S., AND R. G. MURRAY. 1970. Fine structure of degeneration and regeneration in denervated rabbit vallate taste buds. Anat. Rec. 168:383-413. GIROD, S. C., F. W. NEUKAM, B. GIROD, K. REUMANN, AND H. SEMRAU. 1989. The fascicular structure of the lingual nerve and the chorda tympani: an anatomic study. Oral Maniltofuc. Surg. 47:607-609.

13.

14.

15.

GRANT, R., S. MILLER, D. SIMPSON, P. J. LAMEY, AND I. BONE. 1989. The effect of chorda tympani section on ipsilateral and contralateral salivary secretion and taste in man. J. Neurol. Neurosurg. Psychic&-. 52: 1058-1062. GUTH, L. 1963. Histological changes following partial denervation of the circumvallate papilla of the rat. h’xp. Neural. 8: 336349. HAI,PERN, B. P., AND L. M. NELSON. 1965. Bulbar gustatory responses to anterior and to posterior tongue stimulation in the rat. Am. J. Physiol. 209: 105-110.

HELLEKANT, G., Y. KASAHARA, A. I. FARBMAN, S. HARADA, AND C. HARD AF SEGERSTAD. 1987. Regeneration ability of fungiform papillae and taste-buds in rats. Chem. Senses 12: 459-465. HOFFMEISTER, B. 1990. Regeneration der Geschmacksknospen nach Verletzung des Nervus lingualis. Fortschritte der Kiefer- u. Ges~chtsch~rurg~e, BD 35 (G. Pfeifer and N. Schwenzer, Eds.), pp. 125-127. Thieme, Stuttgart. HOSLEY, M. A., S. E. HUGHES, L. L. MORTON, AND B. OAKLEY. 1987. A sensitive period for the neural induction of taste buds. J. Neurosci. 7: 2075-2080. Hou, L.-T., T. P. HETTINGER, AND M. E. FRANK. 1985. Innervation and structure of taste buds in hamsters following unilateral chorda tympani neurectomy. Chem. Senses 10: 444. KINNAMON, J. C. 1987. Organization and innervation of taste buds. Neurobiology of Taste and Smell (T. E. Finger and W. Silver, Eds.), pp. 277-297. Wiley, New York. KINNMAN, E., AND H. ALDSKOGIUS. 1988. Collateral reinnervation of taste buds after chronic sensory denervation: a morphological study. J. Comp. Neurot. 270: 569-574. KRIMM, R. F., M. S. NEZJAD, J. C. SMITH, I. J. MILLER, AND L. M. BEIDLER. 1987. The effect of bilateral sectioning of the chorda tympani and the greater superficial petrosal nerves on the sweet taste in rat. Physiol. Behau. 41: 495-501. LASITER, P. S. 1991. Reorganization of gustatory recipient zones in the nucleus of the solitary tract (NST) following early postnatal receptor damage: Evidence for competitive interactions between gustatory axons during postnatal development. Chem. Senses [Abstract], in press. MAY, M., AND W. M. SCHLAEPFER. 1975. Bell’s palsy and the chorda tympani nerve: A clinical and electron microscopic study. Laryngoscope 85: 1957-1975. MILLER, I. J., AND F. E. REEDY. 1990. Variations in human taste bud density and taste intensity perception. Physiol. Behau. 47: 1213-1219. MILLER, ter mice sci. Lett.

29.

MOZSARY, construction

I. J., AND G. WHITNEY. have more vallate taste 360: 271-275.

1989. Sucrose octaacetate-tasbuds than non-tasters. Neuro-

P. G., AND R. A. MIDDLETON. 1984. Microsurgical of the lingual nerve. J. Oral Mu~~~~ofuc. Surg.

re42:

415-420. 30.

NINOMIYA, Y., AND M. FUNAKOSHI. 1987. @alitative discrimination among “umami” and the four basic taste substances in mice. Umami: A Basic Taste (Y. Kawamura and M. R. Kare, Eds.), pp. 365-385. Marcel Dekker, New York.

31.

OAKLEY, B. 1985. Trophic competence in mammalian gustation. Taste, Olfact~n, and t& Central Nervous System (D. W. Pfaff, Ed.), pp. 92-103. Rockefeller Univ. Press, New York.

32.

ROBINSON, P. P. 1989. The reinnervation vary glands 259-271.

after

lingual

nerve

injuries

of the tongue and saliin cats. Brain Res. 483:

33.

SPECTOR, A. C., G. SCHWARTZ, AND H. J. GRILL. 1988. Chemospecific deficits in taste detection following bilateral chorda tympani section in rats. &cm. Senses 13: 738.

34.

SPECTOR, A. C., G. J. SCHWARTZ, AND H. J. GRILL. 1990. Chemospecific deficits in taste detection after selective gustatory deafferentation in rats. Am. J. Physiol. 258: R820-R826.

35.

TOYOSHIMA, K. 1989. Fine structural and histochemical lingual taste organs of Rana cetesbeiuna (Anura:Ranidae) planted to liver. J. Morphol. 200: 29-36.

16. HART) AF SEGERSTAD,

C., G. HELLEKANT, AND A. I. FARBMAN. 1989. Changes in number and morphology of fungiform taste buds in rat after transection of the chorda tympani or chorda-lingual nerve. Chem. Senses 14: 335-348.

HAUSAMEN, J. E. 1983. Zur Indikation der Mikrochirurgie. Fortschritte der Kiefer-und Gesichtschirurgie, BL, 28 (G. Pfeifer and N. Schwenzer, Eds.) pp. 163-167. Thieme, Stuttgart.

28.

286.

63

INJURY

study of trans-

64 36.

37.

38.

BARRY

AND

FRANK

TRAVERS, J. B., H. J. GRILL, AND R. NORGREN. 1987. The effects of glossopharyngeal and chorda tympani nerve cuts on the ingestion and rejection of sapid stimuli: An electromyographic analysis in the rat. Behuv. Brain Res. 25: 233-246. WAGNER, C. E. 1954. The Fate of Denervated Taste Buds in Normal and Regenerating Barbels of the Catfish Doctoral dissertation, Department of Zoology, Indiana University.

39.

WHITEHEAD, M. C., M. E. FRANK, T. P. HETTINGER, L.-T. Hou, AND H.-D. NAH. 1987. Persistence of taste buds in denervated fungiform papillae. Brain Res. 405: 192-195.

41.

40.

WIBERG, A. 1971. Function of the Chordu Tympani before and after Operation for Clinical Otosclerosis, Dissertation, University of Umea, Umea, Sweden. YAMAMOTO, T., R. MATSUO, Y. KIYOMITSU, AND R. KITAMURA. 1988. Taste effects of ‘umani’ substances in hamsters as studied by electrophysiological and conditioned taste aversion techniques. Brain Res. 451: 147-162. ZALEWSKI, A. A. 1969. Role of nerve and epithelium in the regulation of alkaline phosphatase activity in gustatory papillae. Exp. Neurol. 23: 18-28.

Response of the gustatory system to peripheral nerve injury.

Peripheral taste nerve damage occurs as a result of disease and surgery. The response depends on the taste field affected and the species. Nerve regen...
1MB Sizes 0 Downloads 0 Views