Unilateral Chorda Tympani Research Articles

Influences of age, tongue region, and chorda tympani nerve sectioning on signal detection measures of lingual taste sensitivity

Although the ability to taste is critical for ingestion, nutrition, and quality of life, a clear understanding of the influences of age, sex, and chorda tympani (CT) resection on taste function in different regions of the anterior tongue is generally lacking. In this study we employed criterion-free signal detection analysis to assess electric and chemical taste function on multiple tongue regions in normal individuals varying in age and sex and in patients with unilateral CT resections. The subjects were 33 healthy volunteers, ranging from 18 to 87years of age, and 9 persons, 27 to 77years of age, with unilateral CT lesions. The influences of age, sex, tongue region, and chorda tympani resections on signal detection sensitivity (d′) and response bias (β) measures was assessed in 16 tongue regions to weak electric currents and solutions of sucrose, sodium chloride, and caffeine. Significant age-related decrements in d′ were found for sucrose (p=0.012), sodium chloride (p=0.002), caffeine (p=0.006), and electric current (EC) (p=0.0001). Significant posterior to anterior, and medial to lateral, gradients of increasing performance were present for most stimuli. β was larger on the anterior than the posterior tongue for the electrical stimulus in the youngest subjects, whereas the opposite was true for sucrose in the oldest subjects. No sex differences were apparent. d′ was depressed ipsilateral to the CT lesion side to varying degrees in all tongue regions, with the weakest influences occurring on the medial and anterior tongue. CT did not meaningfully influence β. This study is the first to employ signal detection analysis to assess the regional sensitivity of the tongue to chemical and electrical stimuli. It clearly demonstrates that tongue regions differ from one another in terms of their age-related sensitivity and their susceptibility to CT lesions.

C-Fos-like Immunoreactivity in the nucleus of the solitary tract following taste stimulation of the contralateral side of the tongue

Taste receptors of the anterior tongue are innervated by the chorda tympani (CT) branch of the facial (VIIth) nerve. The CT nerve transmits information on taste to the ipsilateral nucleus of the solitary tract (NST), which is the first taste central nucleus in the medulla. Taste information is known to be transferred ipsilaterally along the taste pathway in the central nervous system. Some patients with unilateral CT damage often retain their ability to sense taste. This phenomenon is not explained by the unilateral taste pathway. We examined whether neurons in the NST receive information on taste from the contralateral side of the tongue by measuring c-Fos-like Immunoreactivity (cFLI) following taste stimulation of the contralateral side of the tongue in the anesthetized rats. We used four basic taste stimuli, 1.0 M sucrose, 0.3 M NaCl, 0.01 M citric acid, 0.03 M QHCl, and distilled water. Stimulation of one side of the tongue with taste stimuli induced cFLI in the NST bilaterally. The mean number of cFLI ranged from 23.28 ± 2.46 by contralateral QHCl to 30.28 ± 2.26 by ipsilateral NaCl stimulation. The difference between the number of cFLI in the ipsilaterl and contralateral NST was not significant. The result of the current study suggests that neurons in the NST receive information on taste not only from the ipsilateral but also the contralateral side of the tongue.

Aging profoundly delays functional recovery from gustatory nerve injury

The peripheral taste system remains plastic during adulthood. Sectioning the chorda tympani (CT) nerve, which sends sensory information from the anterior tongue to the central nervous system, causes degeneration of distal fibers and target taste buds. However, taste function is restored after about 40 days in young adult rodents. We tested whether aging impacts the reappearance of neural responses after unilateral CT nerve injury. Taste bud regeneration was minimal at day 50–65 after denervation, and most aged animals died before functional recovery could be assessed. A subset (n=3/5) of old rats exhibited normal CT responses at day 85 postsectioning, suggesting the potential for efficient recovery. The aged taste system is fairly resilient to sensory receptor loss and major functional changes in normal aging. However, injury to the taste system reveals a surprising vulnerability in old rodents. The gustatory system provides an excellent model to study mechanisms underlying delayed recovery from peripheral nerve injury. Strategies to accelerate recovery and restore normal function will be of interest, as the elderly population continues to grow.

Taste-responsive neurons in the nucleus of the solitary tract receive gustatory information from both sides of the tongue in the hamster

Taste receptors on the left and right sides of the anterior tongue are innervated by chorda tympani (CT) fibers, which carry taste information to the ipsilateral nucleus of the solitary tract (NST). Although the anterior tongue is essential for taste, patients with unilateral CT nerve damage often report no subjective change in their taste experience. The standing theory that explains the taste constancy is the "release of inhibition", which hypothesizes that within the NST there are inhibitory interactions between inputs from the CT and glossopharyngeal nerves and that the loss of taste information from the CT is compensated by a release of inhibition on the glossopharyngeal nerve input. However, the possibility of compensation by taste input from the other side of the tongue has never been investigated in rodents. We recorded from 95 taste-responsive neurons in the NST and examined their responsiveness to stimulation of the contralateral CT. Forty-six cells were activated, mostly with excitatory responses (42 cells). Activation of NST cells induced by contralateral CT stimulation was blocked by microinjection of lidocaine into the contralateral NST but was not affected by anesthetization of the contralateral parabrachial nuclei (PbN). In addition, the NST cells that were activated by contralateral CT stimulation showed reduced responsiveness to taste stimulation after microinjection of lidocaine into the contralateral NST. These results demonstrate that nearly half of the taste neurons in the NST receive gustatory information from both sides of the tongue. This "cross talk" between bilateral NST may also contribute to the "taste constancy".

Rapid Changes in Gustatory Function Induced by Contralateral Nerve Injury and Sodium Depletion

The combination of dietary sodium depletion and unilateral chorda tympani (CT) nerve section decreases sodium taste function in the intact CT nerve. However, functional changes have not been examined prior to day 4 postsectioning, even though degenerative and inflammatory responses are robust during that period. Rats received unilateral CT section and/or dietary sodium depletion, accomplished by 2 injections of furosemide and a sodium-restricted diet, on day 0. Surgical controls received sham nerve sectioning. At days 1, 2, 3, or 4, taste responses were recorded from the intact nerve. Functional changes were rapid and unexpected. At day 1 postsectioning, neural responses from the uninjured CT of both control-fed and sodium-depleted animals were reduced. By day 2, however, normal function was restored in control-fed rats, whereas functional deficits persisted in depleted animals. Sodium depletion alone also induced a transient decrease in sodium responses at days 2-3 after furosemide injection. These results demonstrate that distant neural injury can elicit gustatory plasticity regardless of the dietary environment, but normal responses can be restored. We suggest that neutrophils mediate the initial postinjury deficits in taste function, whereas macrophages promote the recovery of normal function.

Upregulation of the chemokine monocyte chemoattractant protein-1 following unilateral nerve injury in the peripheral taste system

Macrophages are recruited to both sides of the tongue following unilateral chorda tympani (CT) nerve injury. The mechanisms responsible for recruiting these macrophages to the peripheral taste system are unknown. Neural degeneration in other systems leads to the upregulation of small molecules that function as chemoattractant cytokines, or chemokines. The chemokines monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-1α are important regulators of macrophage recruitment to sites of infection and injury. We hypothesized that CT nerve sectioning leads to a bilateral upregulation of MCP-1 and MIP-1α. We examined lingual protein levels of MCP-1 and MIP-1α by enzyme-linked immunosorbent assays (ELISA)s at several time points after unilateral CT section in rats. MCP-1 was significantly upregulated on the intact side of the tongue at 12 h after sectioning, and on the injured side at 24–48 h post-injury. However, MIP-1α expression did not significantly change following CT nerve sectioning. These data indicate that chemokines are differentially regulated following neural injury, and that MCP-1 may contribute to the bilateral macrophage response to neural injury. Furthermore, the increase in MCP-1 occurs even in uninjured, distant sites, and may be upstream from the deficits in neural responses from the contralateral CT after sectioning.

Lipopolysaccharide-induced up-regulation of activated macrophages in the degenerating taste system

Unilateral chorda tympani (CT) nerve section and maintenance on a sodium-restricted diet leads to a rapid decrease in neurophysiological taste responses to sodium in the contralateral, intact CT nerve. Up-regulation of immune function with lipopolysaccharide (LPS; 100 microg i.p.) induces a recovery of normal sodium taste responses, suggesting that the sodium-deficient diet is immunosuppressive. In fact, there is a bilateral increase in the number of lingual, activated macrophages in control-fed rats receiving CT nerve section that does not occur in sodium-deficient rats after sectioning. In the current study, we hypothesized that the LPS-induced recovery of normal taste function in sodium-deficient rats is based on an increase in the activated macrophage response to denervation. Rats receiving a unilateral CT nerve section, a sodium-restricted diet, and/or an injection of LPS (100 microg; i.p.) were overdosed with pentobarbital at day 2 postsectioning, and tongues were rapidly dissected and frozen. Cryosections were then immunohistochemically stained to determine the percentage of ED1 staining for activated macrophages or the number of alphabeta or gammadelta T cells. Activated macrophage levels were significantly increased in sodium-restricted rats that received LPS following unilateral CT nerve section, supporting our hypothesis. These novel findings suggest that LPS overcomes the immunosuppression induced by the sodium-restricted diet and also indicate that the immune system plays a role in regulating taste function after neural injury.

Nerve-Target Interactions in the Gustatory System Following Unilateral Chorda Tympani Nerve Section

Although much effort has been directed at examining the morphological characteristics of denervated and regenerated taste buds, relatively little is known about the physiology of reinnervated taste cells (Vintschgau and Honigschmied, 1876; Guth, 1957; Fujimoto and Murray, 1970; Cheal and Oakley, 1977; Whitehead et al., 1987). Over 25 years ago, Oakley (Cheal et al., 1977) and colleagues found that some chorda tympani fibers reinnervated fungiform papillae on the gerbil’s anterior tongue in <2 weeks post-sectioning. Studies that examined recovery of taste function following nerve damage (Cain et al., 1996; Cheal et al., 1977; Ninomiya, 1998; Yasumatsu et al., 2003) indicate that regenerated taste nerves generally recover normal function after progressing through a transitional period. Only relatively recently has the impact of environment on the adult regenerating taste system been explored. Regenerating taste receptor cells in adult rats are susceptible to dietary influences (Hill and Phillips, 1994). Sectioning the chorda tympani unilaterally in rats fed a sodium-restricted diet at adulthood resulted in a regenerated nerve that had attenuated responses to sodium salts. Responses to other stimuli were unaffected. In addition, there were other, novel effects. In the same rat, the contralateral, uncut nerve was supersensitive to sodium salts. The supersensitivity developed progressively following an initial

Effects of the chorda tympani damage on submandibular glands: scintigraphic changes.

The aim of this study is to compare the scintigraphic results of a denervated submandibular gland with the contralateral normal side in patients with unilateral chorda tympani damage. Sixteen patients (11 women and five men with a mean age of 27) with unilateral proven chorda tympani damage during their previous ear surgery were included in the study. The perfusion ratio (PR), concentration ratio (CR) and stimulated excretion ratio (SER) were calculated scintigraphically and the results from the salivary glands on opposite sides were compared. For submandibular glands, the perfusion ratio (PR), concentration ratio (CR) and stimulated excretion ratio (SER) were found to be 0.65 +/- 0.21, 0.70 +/- 0.21, 0.79 +/- 0.37, respectively. All ratios resulted from statistically decreased radioactivity accumulation on the affected side (p<0.05). Chorda tympani damage negatively affects the function of the ipsilateral submandibular glands despite the absence of atrophy. Dynamic salivary gland scintigraphy is a practical and valuable method of disclosing the decreased capacity of perfusion, concentration and secretion function in unilateral neurological deprivation.

The effects of the chorda tympani damage on submandibular glands: biometric changes

Objective: It was aimed to analyze the biometric changes in ipsilateral submandibular glands of patients with unilateral chorda tympani (ChT) section during otological operations, compared with change in size of the contralateral glands and with those of healthy subjects. Methods: 29 patients with unilateral complete ChT section and 29 healthy subjects with identical ages, genders, and weights to the patient group were examined ultrasonographically. The patients having a mean duration to follow-up examination of 32 months (2–84 months) were subdivided into two groups by their time to follow-up as short-term patient group (2–12 months, 14 patients) and long-term patient group (13–84 months, 15 patients). The ultrasonographic dimensions and volumes of submandibular glands were compared statistically between the groups. Results: In the patient group, the glands on the contralateral, non-operated side were found to be greater than the ipsilateral, denervated glands in terms of both paramandibular depth dimension ( P<0.05) and volume ( P<0.01). The differences could be determined only in long-term patient group. When comparing the submandibular glands of the patient group with those of the control group, it was found that paramandibular depth dimension and volume of the submandibular glands on the contralateral, non-operated side were statistically greater ( P<0.01). There was no difference between submandibular glands on the operated side of the patient group and those of the control group ( P>0.05). Conclusion: The late (13–84 months) biometric results of ChT damage on submandibular gland were significant for increase in the size of the contralateral, non-denervated submandibular gland. An atrophying effect was not ascertained in the submandibular glands denervated parasympathetically due to the section of the ChT.

Effect of stress and cyclosporine on ornithine decarboxylase activity in rat submaxillary lymph nodes

This study was performed: (1) to assess whether the stress produced in rats by daily turpentine oil injections for 5 days, or by restraining the animals for 30 min during 5 days, affected basal and Freund's adjuvant-stimulated submaxillary lymph node ornithine decarboxylase activity, an indicator of cell proliferation; (2) to analyze whether the activity of the immunosuppressive drug cyclosporine on submaxillary lymph node ornithine decarboxylase activation after Freund's adjuvant injection was modified in stressed rats; (3) to examine the mediation of stress effects on submaxillary lymph node ornithine decarboxylase activation by regional sympathetic or parasympathetic nerves. Animals subjected to a unilateral superior cervical ganglionectomy, or to a unilateral chorda tympani section, together with a contralateral sham-operation were employed. After turpentine oil or restraint stress, a significant decrease in submaxillary lymph node ornithine decarboxylase was found. A unilateral sympathetic denervation of submaxillary lymph nodes counteracted in part the inhibitory effect of stress on ornithine decarboxylase activation, as well as augmented the enzyme response in innervated submaxillary lymph nodes. Ornithine decarboxylase activation attained similar values in parasympathetic decentralized or intact submaxillary lymph nodes and the unilateral parasympathetic decentralization did not interfere with the inhibition of enzyme activity found in turpentine oil-stressed rats. Cyclosporine administration (5 or 20 mg/kg) significantly decreased Freund's adjuvant-induced ornithine decarboxylase activity in the submaxillary lymph nodes of control rats, but failed to modify it in turpentine oil-stressed animals. In this latter group, a higher (40 mg/kg) dose of cyclosporine decreased ornithine decarboxylase activity on the innervated side only. A diminished inhibitory response to cyclosporine was found in the parasympathetic decentralized submaxillary lymph nodes of unstressed rats. The results support the view that the immunosuppressive effects of cyclosporine may diminish during stress, in part due to changes in the traffic of neural signals in local sympathetic nerves.

Cyclosporine effect on ornithine decarboxylase activity in rat submaxillary lymph nodes. Modulation by parasympathetic nerves

This study was performed: (1) to assess whether cyclosporine affected the increase in submaxillary lymph node ornithine decarboxylase activity induced by complete Freund's adjuvant injection to rats bearing a regional parasympathetic decentralization; (2) to examine the effect of cyclosporine on cholinergic markers in submaxillary lymph nodes of rats injected with complete Freund's adjuvant or its vehicle. The unilateral parasympathetic decentralization of the submaxillary lymph nodes was achieved by unilateral chorda tympani section; each rat was also contralaterally sham-operated. A 73% decrease of choline acetyltransferase activity and a 78% decrease of neuronal [ 3H]choline uptake, were found in the ipsilateral side 2 weeks after surgery. Cyclosporine (5 or 20 mg/kg) or its vehicle was s.c. injected once daily for 5 days. Freund's complete adjuvant or its vehicle was injected s.c. 1 h before the 3rd injection of cyclosporine. The animals were killed 2 h after the last cyclosporine injection. Parasympathetic decentralization of the submaxillary lymph nodes was followed, 2 weeks later, by a significant inhibition of cyclosporine activity on Freund's adjuvant-induced ornithine decarboxylase. In rats injected with complete Freund's adjuvant or its vehicle, sympathetic denervation of submaxillary lymph nodes achieved by unilateral superior cervical ganglionectomy, augmented the stimulatory activity of cyclosporine on choline acetyltransferase and neuronal choline uptake. Cyclosporine treatment did not modify the total [ 3H]choline uptake, regardless of Freund's adjuvant injection or of intactness of the sympathetic innervation. Choline acetyltransferase and choline uptake were significantly augmented by the injection of Freund's adjuvant alone. The results indicate that an appropriate parasympathetic local environment is needed for cyclosporine immunomodulation in lymphoid tissue, and that cyclosporine augmented cholinergic activity in submaxillary lymph nodes, an effect amplified by regional sympathetic denervation. Cholinergic markers in lymphoid tissue increased during the immune reaction.

The effect of unilateral chorda tympani damage on taste.

Patients with localized damage to the taste system often experience no subjective change in real-world taste experience. In an effort to understand this, eight patients who recently underwent acoustic neuroma removal were evaluated for taste loss. Localized taste testing showed that taste intensities decreased in the distribution of cranial nerve VII ipsilateral to tumor removal as expected, but asymmetries occurred for IX. Intensities were greater on the side contralateral to the tumor removal. In addition, palatal taste, also thought to be mediated by VII, was not totally abolished. It is concluded that cranial nerve IX is normally inhibited by cranial nerve VII in the taste network. When VII is damaged, this inhibition is abolished. This release of inhibition serves as a compensation mechanism that preserves normal taste experience.

Ion transport across lingual epithelium is modulated by chorda tympani nerve fibers

Each chorda tympani (CT) nerve innervates taste cells in fungiform papillae on one side of the anterior two-thirds of mammalian tongues. In this study, three effects of unilateral CT transection were investigated: (1) the persistence of taste cells on the ipsilateral and contralateral sides; (2) the ability of the CT to modulate ion transport across the ipsilateral and contralateral sides of canine lingual lingual epithelia; and (3) the effect on contralateral CT responses. Unilateral transection of dog CT caused the mean number of taste buds/fungiform papilla on the ipsilateral side to decrease from five to zero by 29–30 days after surgery. Taste buds reappeared after 44 days but in reduced numbers (two taste buds/papilla). This reappearance of taste buds after 44 days is consistent with the time predicted for the CT to regenerate and each the anterior portion of the tongue. The number of taste buds/papilla remained unchanged on the contralateral side. Measurements of the short-circuit current (Isc) across bothe ipsilateral and contralateral sections of isolated canine lingual epithelia were performed at various times after unilateral CT transection. Both sides responded similarly. The Isc began to decline after 3 days, reached a minimum after ∼ 18 days (∼ 40% of control Isc) and increased to control values after ∼ 40 days. This includes experiments performed 30 days after surgery, when no taste buds were present on the ipsilateral side and the Isc was 80% of control values. For all times after CT transection, amiloride, an epithelial Na + channel blocker, inhibited Isc. Thus, epithelial cells in dog tongue have amiloride-inhibitable pathways. These results show that proteins involved in active Na + transport across lingual epithelia can be modulated by CT nerve fibers.

The effect of chorda tympani section on ipsilateral and contralateral salivary secretion and taste in man.

Bilateral chorda tympani section is an accepted treatment for troublesome sialorrhoea. Nevertheless the effects of this operation have been poorly studied. Twenty patients were studied with unilateral chorda tympani section and a healthy contralateral ear. The effects on ipsilateral and contralateral stimulated submandibular and parotid flow and taste recognition and detection thresholds were measured. Stimulated submandibular flow accounted for only 27% of the total salivary flow. Chorda tympani section had no effect on submandibular flow in seven patients and only reduced submandibular flow by approximately 54% in the remaining 13 patients. No significant effect was observed on ipsilateral parotid flow rate. Electrogustometric taste detection thresholds were more than twice the accepted upper limit of normal on the lesioned side and taste recognition thresholds were also markedly abnormal. Chorda tympani section alone is a poor method of reducing stimulated salivary flow.

Surgical Management of Sialorrhea

At the annual meeting of the American Academy of Otolaryngology–Head and Neck Surgery in Washington, DC, Sally R. Shott and colleagues of the Children's Hospital Medical Center, Cincinnati, reported their results with the surgical management of sialorrhea. In a retrospective telephone interview of parents and caretakers, they found none of six patients improved by submandibular duct rerouting alone; five of 20 patients improved by submandibular duct rerouting, bilateral tympanic neurectomy, and unilateral chorda tympani division; none of two patients improved by bilateral tympanic neurectomy and bilateral submandibular gland excision; and 11 of 14 patients improved by bilateral submandibular gland excision and bilateral parotid duct ligation. The latter procedure is now their treatment of choice in the surgical management of sialorrhea. This marks a change in policy since a 1981 publication from the same institution identifying bilateral submandibular duct rerouting as their procedure of choice. With the new procedure they report

Denervation-induced changes in cell proliferation in the rat molar after wounding.

The dental pulp has the capacity to initiate and maintain repair after trauma. The purpose of the present study was to quantitatively analyze the role of the peripheral nervous system in regulation of pulpal cell proliferation in response to wounding. Six groups of ten rats were used in these studies. There was one baseline group (wounded, but innervation intact) and five resection groups. The resection groups included rats with unilateral superior cervical ganglionectomy (SCG), unilateral inferior alveolar nerve resection (IAN), unilateral chorda tympani (CT) resection, IAN + SCG, or a complete unilateral nerve resection (IAN + SCG + CT). One millimeter of enamel and dentin was removed from the first mandibular molar on the experimental (resected) side. Therefore, each rat had an experimental and control molar. Rats were killed at various intervals from day 0 to day 15 after wounding and received 0.5 muCi/g b.wt. 3H-thymidine 1 hour before death. For the baseline (innervation intact) data a peak in 3H-thymidine incorporation occurred at 5 days after wounding. In the resected groups, there was a general increase in the number of labeled cells at the zero time point, and a suppression of the 5-day peak with a delay in the proliferative response to wounding. The SCG + IAN-resected group maintained the lowest number of labeled cells throughout the entire experimental period compared to the experimental baseline data and the two controls. At the initial and termination points the SCG + IAN-resected groups demonstrated the highest number of labeled cells.(ABSTRACT TRUNCATED AT 250 WORDS)