Taste changes in orofacial pain conditions and coronavirus disease 2019: a review

Introduction

Taste is one of the primordial sensations with an important role in nutrition and survival instincts of an organism. Changes in taste perception are reported to occur in approximately 0.6–7.2% of the adult population (1,2). The variations in the prevalence of taste changes may be attributed to differences in the study population, criteria, and methods used to assess taste alterations. Age and sex related differences have also been reported in the prevalence of taste changes. An epidemiological study by Bergdahl et al., estimated the prevalence of taste changes in 2.5% of the subjects assessed (0.9% in males and 3.8% in females) (3). The study also reported variations in the prevalence of taste changes among groups stratified based on the age (second to the sixth decade) and in males and females; males (no cases were reported in the second and sixth decade, 1.9% in the third decade and 1.8% in the fourth decade) and females (1% the second decade, 3.8% in the third decade and increasing to 5.1% in the sixth decade (3). Taste changes are often distressing to the patients and affect their quality of life (4,5).

Alterations in taste may be physiological or secondary to local, systemic factors such as coronavirus disease 2019 (COVID-19) and syndromes such as burning mouth syndrome (BMS). Taste changes may be qualitative or quantitative. Quantitative changes in taste such as ageusia (complete loss of taste), hypogeusia (diminished taste sensation), hypergeusia (enhanced perception of taste) and qualitative changes such as dysgeusia (altered/distorted taste sensation) and phantogeusia (taste phantoms like metallic/bitter taste in absence of stimulation) (6). A significant proportion of patients with taste changes present to the dental and medical healthcare professionals. Taste phantoms in the absence of any stimulation are a significant source of distress to patients. The review aims to familiarize dental and medical healthcare professionals with physiological and common pathophysiological mechanisms which can induce changes in taste and briefly discuss diagnosis and management strategies.

Methods

Indexed databases (PubMed, EMBASE, Scopus, ISI Web of Knowledge, Medline, OVID, Scopus, Cochrane library) were searched using the keywords ((“taste”[MeSH Terms] OR “taste”[All Fields] OR “tastes”[All Fields] OR “tasting”[All Fields] OR “tasted”[All Fields] OR “tasteful”[All Fields] OR “tastings”[All Fields]) AND (“change”[All Fields] OR “changed”[All Fields] OR “changes”[All Fields] OR “changing”[All Fields] OR “changings”[All Fields]) AND (“taste”[MeSH Terms] OR “taste”[All Fields] OR “tastes”[All Fields] OR “tasting”[All Fields] OR “tasted”[All Fields] OR “tasteful”[All Fields] OR “tastings”[All Fields]) from January 1st 1918 to October 31st 2020 independently by 2 authors (JK, MK). In case of disagreement, a consensus was obtained by discussion and involving a third author (NN). Research studies, clinical trials, randomized controlled trials, case reports, books, documents, narrative reviews, systematic reviews and meta analysis in English were included. Letters to the editor, commentaries were excluded.

Taste pathway

Taste sensation is complex and encompasses both the innate and learned components (7). Sensory perception for taste has been identified for at least five different modalities including sweet, sour, salt, bitter and umami. Recently, taste receptors for fat have been identified and considerable debate exists on whether fat should be considered an additional taste sensation or if it plays just a role in modifying other tastes such as umami (8). Tongue maps describing specific areas of the tongue for different tastes are now considered to be redundant (9). Current findings suggest that all areas of the tongue are capable of perceiving different taste sensations but some areas are more specific.

Taste sensation from the anterior 2/3rd of the tongue is carried by the chorda tympani nerve (a branch of the facial nerve), posterior 1/3rd by glossopharyngeal nerve and epiglottis by the vagus nerve. Taste sensation from the palate is carried by the greater petrosal nerve, a branch of the facial nerve. Lingual nerve (a branch of the trigeminal nerve) is the general sensory afferent (10). The perception of taste is initiated by the dissolution of molecules and activation of various taste receptors (11). Taste receptors are present on taste cells located within the taste buds. Four types of taste cells Type I–IV have been identified; Type I (similar to astrocytes), Type II (respond to sweet, bitter, umami), Type III (sour and salty) and Type IV (immature cells). Each taste cell is specific to a particular taste; however, taste buds have multiple taste cells (each of which may respond to a different taste) and are thus nonspecific (8). Taste buds are thus capable of responding to more than one taste. Taste buds are located primarily in the fungiform papilla and to a lesser extent on the circumvallate and foliate papilla (12,13). Fungiform papillae have been shown to contain multiple taste buds and each taste bud is encircled by afferent neurons transmitting pain sensation in a basket like formation. The taste buds are distributed at various sites in the alimentary canal; predominantly in the epithelium of the dorsum of the tongue and to a lesser extent in the palate, pharynx, superior third of esophagus and epiglottis. Studies have reported taste receptors in the gut and nasal passages as well (14-16).

At the receptor level in the taste buds, chemical signals from the various molecules are transduced to electrical signals which are carried from the peripheral nervous system (PNS) to the central nervous system (CNS) by the afferent nerves. During the process of transduction, Type II taste cells utilize G protein-coupled receptors with ATP as the primary neurotransmitter; Type III cells use voltage gated calcium channels and 5-HT as the primary neurotransmitter (8). Following transduction, the afferent impulses relay to the nucleus tractus solitaries (NTS) and from there they synapse at the thalamus and proceed to the somatosensory cortex. Variations have been described in the projection pathway of the second order neurons to the thalamus and somatosensory cortex. The second order neurons from NTS synapse at the thalamus and a majority project to the ipsilateral cerebral cortex; few may cross to opposite side and project to the contralateral cerebral cortex and on rare occasions few fibers may have bilateral representation (10,17-19). Taste sensation is finally interpreted by the primary and secondary taste centers of the insular cortex (20). Imaging studies have shown that taste sensation for sweet and salt are readily distinguishable, however bitter taste is associated with an avoidance behavior causing deactivation of the primary gustatory complex as a protective response (21).

The final perception of taste involves integration of multiple somatosensory and olfactory modalities (7). The pathways for smell and taste frequently interact. In addition to the activation of taste receptors, the touch receptors present in the oral cavity are also activated on consumption of food and enable localization of taste. Following the dissolution of molecules in food, the volatile components also stimulate the olfactory receptors which are located on the roof of the oral cavity through retro nasal olfaction leading to smell and recognition of food (7).

Taste changes and physiological variations

Taste changes may be result of physiological factors like aging, pregnancy, menopause, ethnic and genetic variations. Elderly subjects report a decrease in salt and bitter taste acuity (22,23) and elevated taste threshold (24). Age related changes, hyposalivation, co morbid medical conditions, concurrent medications (3), vitamin and mineral deficiencies may play a role in inducing taste alterations in elderly. Taste changes especially bitter taste perception are frequently reported in pregnant females with complaints of hyperemesis (25) which is more pronounced in the first trimester . According to Duffy et al., this may be a normal protective mechanism to prevent ingestion of poisonous substances which have a bitter taste (26). Genetic and ethnic variations have also been reported with higher taste sensations among Hispanics and African Americans (27).

Taste and pain

Taste mediated suppression of pain may also be related to central mechanisms. Sucrose mediated suppression of pain occurs rapidly and lasts for a very short period (few minutes) (28,29). This effect was suggested to be naltrexone dependent in rats (29,30) and in humans (31,32), suggesting opioid dependency of the mechanism. Centers involved in opioid dependent pain [rostral ventromedial medulla (RVM) and the periaqueductal gray (PAG)] (33,34) mediate pain suppression via descending pathways. Study has shown that Fos expression was induced in the PAG and RVM following sucrose administration (35).

Taste and BMS

The International Classification of Orofacial Pain (ICOP) defines BMS as “An intraoral burning or dysaesthetic sensation, recurring daily for more than 2 hours per day for more than 3 months, without evident causative lesions on clinical examination and investigation” (36). The diagnosis is based on exclusion of local and systemic factors which cause burning sensation. BMS was previously referred to by various terminologies such as glossodynia, glossopyrosis, oral dysesthesia, primary BMS, idiopathic BMS and stomatodynia (36,37). Majority of the epidemiological studies especially the older ones are flawed with the lack of clear diagnostic criteria, poor methodology and failure to distinguish BMS from BMSs. This has resulted in wide variations in the estimated prevalence of BMS from 1–15% (38). The condition has a female predominance and has the highest prevalence in the 5th and 6th decade (38,39). The intensity of pain in BMS varies from mild to severe, and may be continuous/intermittent at single or multiple sites in the oral and perioral structures (most common is the tongue followed by palate, lips, buccal mucosa). Majority of the cases present with symmetric bilateral involvement of affected structures (20). Pain often amplifies as the day progresses; but does not interfere with the sleep. BMS patients often report subjective somatosensory changes such as taste changes, taste phantoms, hypo salivation, and improvement in pain with consumption of sweet food (39,40). It is estimated that 11-68% of patients with BMS report taste dysfunction (41-44) and approximately 2/3rd of the patients report subjective xerostomia, and dysesthesia (36). Approximately 1/3 of post-menopausal women (42) report taste changes and it is predominant in patients experiencing a combination of dysgeusia, burning/pain and oral dryness.

Symptoms of burning sensation in the oral and perioral structures may be secondary to local (trauma from intraoral prosthesis such as dentures, candidiasis, xerostomia, contact allergy, post radiation/chemotherapy mucositis, and mucosal lesions such as aphthous ulcers, lichenoid reactions, herpes) and systemic factors such as diabetes, autoimmune disorders such as Sjogren’s syndrome, lichen planus, vitamin and micronutrient deficiencies (niacin, iron, vitamin B-12, or folic acid, zinc), hypothyroidism, medications (e.g., ACE inhibitors), gastro esophageal reflux disease (45). Burning symptoms secondary to local and systemic factors was previously referred to as secondary BMS (37). Taste changes are frequently seen in many BM conditions. Distinction between BMS and BM is crucial for successful treatment. Treatment of the underlying pathologies results in complete resolution of symptoms in patients with BM. Taste changes associated with burning mouth have been described in the section of taste changes secondary to local and systemic factors (Table 1).

Theories of taste changes in BMS

Disinhibition theory

Mounting evidence from animal and human studies suggests that taste sensation specifically sweet sensation has the ability to inhibit pain (28,57-61) ipsilaterally to contralaterally (62). When one nerve innervating taste is damaged its inhibitory effect on another is lost. This often results in taste phantoms (9), intensification of pain and pain/oral burning. It has been shown that topical application of local anesthetic may enhance burning sensation in patients with BMS (63). The intensification of pain by inhibiting/anesthetizing one nerve supports the previously proposed disinhibition theory. Disinhibition theories have also been supported by quantitative sensory testing (QST) which has shown chorda tympani hypofunction (45,64-67).

Supertaster theory

In 1931, Fox accidentally discovered that he could not taste phenylthiocarbamide (PTC) while his colleague observed a bitter taste. A subsequent evaluation of 2,500 participants revealed that 28% could not taste PTC (referred to as non-tasters); 65.5% observed bitter taste (referred to as tasters); and the rest, reported other taste qualities (68). Fisher later suggested replacement of PTC by 6-n-propylthiouracil (PROP) as it is odorless and less toxic (69). Tasters have been further subclassified into moderate tasters (who perceive PROP to be moderately bitter) and supertasters (who perceive PROP to be severely bitter) (70) based on their perception of taste to PTC/PROP. Genetic variations underlying inability to taste may be related to the number of taste buds and fungiform papillae; with non-tasters having the least number of fungiform papillae and supertasters exhibiting up to four times the number of taste buds compared to non-tasters and exhibiting densely packed smaller fungiform papillae (9,12).

The fungiform papillae have multiple taste buds encircled by afferent neurons transmitting pain sensation in a basket like formation (67). Hence, supertasters exhibiting increased number of fungiform papillae also have an increased number of pain transmitting neurons and a greater predisposition to enhanced perception of oral pain (67,71,72). Contradictory results exist on whether the oral burning is proportional to the density of fungiform papillae with some studies suggesting an association and others refuting the claim (67,73). Family studies have suggested that inability to taste PTC is a mendelian recessive trait (two recessive alleles “tt”) and tasters have one dominant and one recessive or two dominant alleles (Tt/tT or TT) (68). The PROP gene has been localized to chromosome 5 and a region on chromosome 7 (74). Females are more responsive to PTC/PROP (12). However, caution should be excised in the classification of tasters vs. non-tasters as pathologies (hypothyroidism, head injury etc.) may frequently enhance or reduce the perception of taste to PROP and result in misclassification of the groups (75).

Role of gamma-aminobutyric acid (GABA) in taste inhibition

GABA is an inhibitory neurotransmitter found in the taste pathway (76) and GABA receptors have been reported in the CNS/PNS. Patients with BMS have reported good efficacy with GABA agonists such as clonazepam (38). Since, inhibition of taste may produce oral pain/burning it is conceivable that use of GABA agonists may counter the inhibitory effect of taste loss (67) or it may reduce burning sensation to improve taste. A recent study has shown that reduction of oral pain and burning may improve taste (38).

Taste changes in local and systemic pathologies

Mechanical, thermal and chemical irritants may damage the taste buds and thus produce taste changes or taste phantoms. Allergic contact stomatitis, food allergies, additives, preservatives, food flavorings, dental restorations, denture materials, oral care products including mouthwashes may induce changes in taste. A recent animal study on the role of chemicals in dental materials on taste changes has shown inflammatory, atrophic, destructive, sclerotic changes in the intra oral mucous membrane and in the taste buds (77). Mouthwashes containing chlorhexidine gluconate may induce hypogeusia to salt, bitter tastes and dysgeusia; which may last for few weeks even after discontinuation of the mouthwash (78).

Pathologies in the Ear Nose Throat (ENT) such as mastoiditis, purulent otitis media, upper respiratory infections have been reported to induce changes in taste. In these cases, perception of PROP bitterness is also reduced (79). Approximately 31.2% patients with allergic rhinitis report taste disorders (80). Middle ear infections may cause physical damage to chorda tympani and result in taste or sensory intensification or loss of taste and phantoms (79). Taste changes have been reported in mucosal lesions such as lichen planus. The prevalence of taste disorders in oral lichen planus is estimated to be approximately 0.5% (81). However, majority of the patients fail to notice subjective taste loss. Objective quantification of taste loss by Suter and colleagues has suggested that the prevalence may be much higher. Objectively, patients with oral lichen planus may have a decreased perception of sour taste (5). The study reported that the condition itself may affect taste cells or the medications used to treat oral lichen planus may have a secondary effect on taste.

It is estimated that 9–22% of taste disorders may be secondary to drugs (6). A study in Netherlands on approximately 1,645 drugs suggested that 20% of patients may experience dysgeusia and hypogeusia (82). Drugs that have been reported to cause taste changes include beta blockers, ACE inhibitors, calcium channel antagonists, antimicrobials, anti-inflammatory, anti convulsants, endocrine and metabolic drugs, chemotherapeutic agents and drugs for gastrointestinal disorders (83-89). Several medications may induce taste disturbances through chemical interference and their effects on taste receptors during their development and maturity and subsequently induce oral pain through CNS mechanisms such as disruption of tonic inhibitory processes (90). Additional mechanisms may include interaction with taste buds (due to local application, absorption into saliva or chronic use), distortion of taste or olfactory signals, qualitative or quantitative effects of drugs on saliva, drug interactions due to polypharmacy, individual predisposition, dose, duration of drugs (82).

Saliva acts as a solvent for the dissolution of food substances and also protects the taste cells. Various connective tissue disease, autoimmune disorders like Sjogren’s, salivary gland disorders, iatrogenic conditions (such as drug-induced or associated with radiation therapy), anxiety or stress may induce hyposalivation or xerostomia and thus affect taste. Trait anxiety, state anxiety, depression, stress, and female gender have a significant association with subjective oral dryness (3).

Patients with cancer frequently report taste disorders. This may be a consequence of the pathology (example: tongue cancer) or as a result of treatment (surgery, radiation therapy and chemotherapy). Surgery for tumors in the head and neck especially the tongue may damage the nerves supplying taste. Radiation therapy and chemotherapeutic agents may damage the taste buds, nerves and mucosal epithelium. Radiation therapy for head and neck cancer may damage the salivary glands and induce xerostomia or hyposalivation which in turn may affect taste. Xerostomia/hyposalivation may cause candidiasis, lack of solute for dissolution of food molecules, and protective effect on taste buds. Nutritional deficiency (e.g., zinc, vitamin B, iron) secondary to the inability to eat may compound the problem. Following chemotherapy, electro gustatory testing has reported that hypogeusia and hypergeusia may develop in the chorda tympani and greater petrosal nerve area respectively. Hypogeusia for bitter was proportional to number of chemotherapy cycles. Filter paper testing in the same population revealed hypogeusia of the chorda tympani and glossopharyngeal nerve for sweet, salt, sour and greater petrosal nerve for sweet, salt, bitter (91).

Deficiency of iron (anemia), vitamin B12, folate, zinc, vitamin B complex (B1, B2, B6), iron, hemoglobin have been found to have significant association with atrophic glossitis (92). Threshold for sour is slightly higher in patients with iron and zinc deficiency. A study has also suggested that Vitamin E may play a role in development and growth of stem cells in olfactory epithelium and taste buds (93) and thus have a role in taste disorders. Tobacco and its constituents, and alcohol have a bitter taste. It has been previously suggested that PTC tasters are less likely to smoke/consume alcohol and it may have a protective role in certain populations (94,95).

Bacterial (leprosy), viral (Bell’s palsy, HIV, herpes simplex, herpes zoster, COVID-19, dengue, Ramsey hunt, influenza, common cold, Hepatitis C) and fungal infections (candidiasis) are associated with changes in taste (46-54). In several instances, often there is no real-world taste loss even though there is objective loss of taste on anterior 2/3. Taste disturbances in patients with leprosy has been suggested to be secondary to damage to taste buds and nerve fibers carrying taste by leprosy bacillus (96). Hepatitis C patients report higher taste thresholds for sweet and umami (53). Bacterial and viral infection can induce inflammation which activates interferon (IFN) pathways in the taste bud cells and affects mechanisms involved in taste transduction. IFN also plays a role in taste bud cell apoptosis leading to variations in the cell type turnover and proportion of different taste bud cells (97). These mechanisms may result in taste changes.

Endocrine disorders such as hypothyroidism and their effects on taste and burning have been studied. Hypothyroidism may induce dysgeusia for bitter and acid taste and the patients report increased sensitivity to tactile, pain temperature, and tabasco/pepper sauce/spicy food. Hypothyroidism may have inhibitory effect on development and maturation of fungiform papillae. This results in reduced taste perception and disinhibition of the trigeminal system (98,99). Patients with type 2 diabetes are frequently non-tasters to PROP with lesser number of fungiform papillae and also have a low ability to detect sour and bitter (100).

Parkinson’s, seizure disorders, ALS multiple sclerosis, and neurodegenerative diseases such as Alzheimer disease, dementia, are associated with changes in taste and smell (101). Taste changes may precede development of these disorders and may be predictive of progression of Alzheimer dementia and cognitive disturbances (101). Patients undergoing dialysis are likely to have deficiencies of water soluble vitamins B, C due to dialysate and possible dietary restrictions (102).These may lead to taste changes. Taste changes have also been reported in chronic kidney disease (55,56) transplant patients (103), gastro esophageal reflux disease. A case series investigating patients with pontine hemorrhage reported taste deficits in all the patients on the ipsilateral side but all were unaware of the taste loss (104).

Taste changes and COVID-19

Taste loss may be an important predictor symptom in COVID-19. The pooled prevalence of taste changes was estimated to be 41.47% and combined loss of taste and smell was present in 30.04% (105). Taste loss in COVID-19 patients has been proposed to be due to damage of the intra oral mucosal epithelium and secondary to damage to the olfactory epithelium. The SARS-CoV-2 binds and penetrates cells utilizing angiotensin-converting enzyme 2 receptor, which is predominantly expressed on the intra oral epithelial cells (106) and respiratory epithelium. In addition, the virus may induce an inflammatory response and create a barrier to the odor molecules or affect the peripheral and central components of the olfactory pathway. Owing to the contribution of smell to taste perception, COVID-19 patients may exhibit secondary loss of taste (105).

Taste changes and nerve injury

Approximately 31.5% of the patients with upper and middle third facial fractures may present with hypogeusia/ageusia with or without accompanying anosmia/hyposmia (107). Majority of these patients present with the complaints immediately after the trauma and rarely few weeks later. Spontaneous resolution of the complaint is rare and often incomplete even after several years (107). Taste changes are frequently reported after middle ear surgery, tonsillectomy, third molar surgery.

Damage to any component of the taste pathway may result in inability to taste. Taste function is rarely completely lost as it would require damage to multiple nerve, taste receptors and taste pathways. Thus, real world taste loss may be intact even in persons with extensive damage to the tongue or nerves supplying the tongue in spite of clear cut (clear evidence/demonstration) of localized taste loss (108). In a study of anesthesia of the tongue and palate, patients could still perceive taste if they were allowed to swallow (109).

In cases of chorda tympani transection, very few patients report taste loss, few report reduced taste and some patients report taste phantoms. In cases of complete unilateral chorda tympani nerve transection, capsaicin burn was increased on the contralateral side (62) more prominently in supertasters. In cases of bilateral sectioning of the chorda tympani during middle ear surgery, there was loss of taste on anterior 2/3 but no change in whole mouth taste ratings (110).

Ascending taste pathways are predominantly ipsilateral with few contralateral and bilateral representation (10). However, descending taste pathways (gustatory cortex to NTS in medulla) has ipsilateral and greater contralateral projection and this may be partly responsible for the disinhibition of glossopharyngeal by chorda tympani.

Taste changes may also occur subsequent to iatrogenic injuries during dental procedures such as local anesthesia and third molar extractions. Following third molar extraction especially distoangular and vertical impactions; gustatory and sensory changes (especially to salt and bitter) may be observed (111,112). There are variations in subjective and objective recovery patterns for somatosensory and gustatory sensations. Following lingual nerve injury and bitter and sour are the last to recover (113).

Assessment

Damage to any component in the taste pathway may induce taste changes. Subjective and objective testing may be accomplished to detect taste loss. However, a majority of the patients fail to perceive the changes. Real world taste loss may be intact even in persons with extensive damage to the tongue or nerves supplying the tongue (114), in spite of clear cut (clear evidence/demonstration) of localized taste loss (108). Localized taste loss occur in specific regions or to particular tastes (115) and may be partial or complete.

Objective assessment may include whole mouth threshold, quality identification, electro gustatory tests, direct scaling tests, spatial test using cotton tipped applicators, filter disc and psychophysical testing.

Additional laboratory and serological testing may be required to diagnose local and systemic factors, autoimmune conditions. QST may be helpful in instances of iatrogenic nerve injury/ trauma. Imaging modalities like MRI may be helpful in cases of suspected lesions in the CNS (e.g., tegmentum lesion in midbrain or pons, lesions in thalamus, pontine hemorrhage, stroke, pontine hemorrhage) causing taste changes.

QST and BMS

Based on QST profile BMS is further subclassified into BMS with somatosensory changes and BMS without somatosensory changes (116). Electrophysiologic studies in patient with BMS have demonstrated that these patients exhibit elevated taste threshold, electro gustatory threshold (43,45,73) whole mouth threshold (117) to sweet and sour (118) in the regions that contain highest density of fungiform papillae which are innervated by chord tympani.

Management of taste disorders

A detailed history and comprehensive clinical evaluation are essential prior to initiation of treatment. A detailed history may help in identification of precipitating factors such as trauma, allergens, local irritants, medical history, habits (smoking, alcohol). A detailed review of systems should be conducted to identify systemic conditions, offending medications, infections which are likely to induce taste changes. Prodromal symptoms are common in viral infections. A screening cranial nerve examination may identify conditions. Comprehensive extra oral, intra oral, salivary gland, lymph node examination, clinical examination should be conducted to look for intraoral sources such as mucosal lesions, allergens like dental restorations or dental materials in dentures, salivary gland disorders. Diagnosis of contributing local and systemic factors of paramount importance and addressing these is the first step for management of taste disorders. A systematic multidisciplinary approach should be followed to enhance success rate in management of taste disorders. This includes correction of micronutrient deficiencies, identifying and removing medications, allergens that are known to interfere with taste (7), identifying and treating underlying systemic disorders. Several conditions are self-limiting and resolve following acute phase of the disease, e.g., COVID-19, Bells palsy. In case of viral conditions such as COVID-19 it may be part of the presentation and recovery of taste generally occurs within 3 weeks of recovery (106). Treatment with thyroid hormones largely reversed both the taste and smell defects. In one case, taste and smell abnormalities were completely corrected after 16 days of treatment with thyroxine (119).

A systematic review on prophylaxis and management of dysgeusia in cancer patients receiving treatment has suggested that zinc sulfate and amifostine have a limited value in prevention and prophylaxis of taste changes (120). Nutritional counseling may be of benefit in these cases.

Management of oral pain in BMS patients with the use of clonazepam, tri cyclic antidepressants, gabapentinoids, alpha lipoic acid, zinc supplements may help in subjective improvement of taste disorders (38).

Management of taste disturbances secondary to trauma or iatrogenic injury depends on the degree of injury. QST may be of value in diagnosing whether it is purely inflammatory pain or there is actual nerve damage. Iatrogenic nerve injuries accompanied by pure inflammatory neuritis as diagnosed with QST may be treated with steroids in early stages (121). Instances of nerve transection secondary to third molar surgery, middle ear surgeries may benefit from micro neurosurgical repair. There is significant somatosensory and chemosensory/gustatory recovery following micro neurosurgical repair although there is variation in subjective and objective results (122,123). Chorda tympani nerve transections in ENT surgeries treated with surgical repair has led to the regeneration of papilla (124) and improvement in taste (Figure 1).

Figure 1 A paradigm for the evaluation and management of patients with taste alterations.

Effective management is still elusive in idiopathic hypogeusia and dysgeusia. Nutritional counseling may be of benefit. A recent systematic review has concluded that there is very low evidence for use of zinc/to treat taste disturbances in idiopathic taste disorders/zinc deficiencies/chronic renal failure very low evidence for acupuncture in idiopathic dysgeusia and hypogeusia (125,126). Pilocarpine, alpha lipoic acid, transcranial magnetic stimulation, ginkgo biloba has been suggested. However well controlled studies are lacking to allow definitive conclusion (125). Intranasal theophylline methyl propyl paraben has shown promising results in a pilot study with hypogeusia (127). Well conducted RCT’s are required in future to enable us to draw definitive conclusions.

Conclusions

Taste disorders may be the result of normal physiological changes or may be secondary to pathology. A variety of local, systemic factors, BMS and chorda tympani nerve injury may induce taste changes. A detailed clinical history, medical history, review of systems and comprehensive clinical examination are vital/paramount for identification of underlying pathophysiological mechanisms. Multidisciplinary management enhances the rates of success in treatment.

Acknowledgments

Funding: None.

Footnote

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://fomm.amegroups.org/article/view/10.21037/fomm-20-68/coif). JK serves as an unpaid editorial board member of Frontiers of Oral and Maxillofacial Medicine from Jun 2020 to May 2022. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Hoffman HJ, Ishii EK, MacTurk RH. Age-related changes in the prevalence of smell/taste problems among the United States adult population. Results of the 1994 disability supplement to the National Health Interview Survey (NHIS). Ann N Y Acad Sci 1998;855:716-22. [Crossref] [PubMed]
2. Thorstensson B, Hugoson A. Prevalence of some oral complaints and their relation to oral health variables in an adult Swedish population. Acta Odontol Scand 1996;54:257-62. [Crossref] [PubMed]
3. Bergdahl M, Bergdahl J. Perceived taste disturbance in adults: prevalence and association with oral and psychological factors and medication. Clin Oral Investig 2002;6:145-9. [Crossref] [PubMed]
4. Tarlarini C, Greco LC, Lizio A, et al. Taste changes in amyotrophic lateral sclerosis and effects on quality of life. Neurol Sci 2019;40:399-404. [Crossref] [PubMed]
5. Suter VG, Negoias S, Friedrich H, et al. Gustatory function and taste perception in patients with oral lichen planus and tongue involvement. Clin Oral Investig 2017;21:957-64. [Crossref] [PubMed]
6. Fark T, Hummel C, Hahner A, et al. Characteristics of taste disorders. Eur Arch Otorhinolaryngol 2013;270:1855-60. [Crossref] [PubMed]
7. Bromley SM. Neurolocalization of taste disorders. Handb Clin Neurol 2019;164:303-23. [Crossref] [PubMed]
8. Kinnamon SC, Finger TE. Recent advances in taste transduction and signaling. F1000Res 2019;8:F1000 Faculty Rev-2117.
9. Bartoshuk LM. Genetic and pathological taste variation: what can we learn from animal models and human disease? Ciba Found Symp 1993;179:251-62; discussion 262-7. [PubMed]
10. Kamath MG, Prakash J, Tripathy A, et al. Taste pathway: what do we teach? J Clin Diagn Res 2015;9:CL01. [PubMed]
11. Bartoshuk LM. The Functions of Taste and Olfaction. Ann N Y Acad Sci 1989;575:353-61; discussion 361-2. [Crossref] [PubMed]
12. Bartoshuk LM, Duffy VB, Miller IJ. PTC/PROP tasting: anatomy, psychophysics, and sex effects. Physiol Behav 1994;56:1165-71. [Crossref] [PubMed]
13. Whitehead MC, Beeman CS, Kinsella BA. Distribution of taste and general sensory nerve endings in fungiform papillae of the hamster. Am J Anat 1985;173:185-201. [Crossref] [PubMed]
14. Rozengurt E, Sternini C. Taste receptor signaling in the mammalian gut. Curr Opin Pharmacol 2007;7:557-62. [Crossref] [PubMed]
15. Finger TE, Kinnamon SC. Taste isn't just for taste buds anymore. F1000 Biol Rep 2011;3:20. [Crossref] [PubMed]
16. Trivedi BP. Neuroscience: hardwired for taste. Nature 2012;486:S7-9. [Crossref] [PubMed]
17. Principles of neural science. 5th ed. In: Kandel ER JT, Siegelbaum SA, Hudspeth AJ, editor. New York: McGraw-Hill, 2013.
18. Standring S. Gray's Anatomy The Anatomical Basis of Clinical Practice. 40th ed. Standring S. editor. UK: Churchill Livingstone/Elsevier, 2008.
19. Taste and smell: An update. In: Hummel T. Welge-Lussen. A, Bradley PJ. editors. Basel: Karger Medical and Scientific Publishers, 2006.
20. Kolkka-Palomaa M, Jaaskelainen SK, Laine MA, et al. Pathophysiology of primary burning mouth syndrome with special focus on taste dysfunction: a review. Oral Dis 2015;21:937-48. [Crossref] [PubMed]
21. Savic-Berglund I. Imaging of olfaction and gustation. Nutr Rev 2004;62:S205-7; discussion S24-41. [Crossref] [PubMed]
22. Winkler S, Garg AK, Mekayarajjananonth T, et al. Depressed taste and smell in geriatric patients. J Am Dent Assoc 1999;130:1759-65. [Crossref] [PubMed]
23. Frank ME, Hettinger TP, Mott AE. The sense of taste: neurobiology, aging, and medication effects. Crit Rev Oral Biol Med 1992;3:371-93. [Crossref] [PubMed]
24. Fukunaga A, Uematsu H, Sugimoto K. Influences of aging on taste perception and oral somatic sensation. J Gerontol A Biol Sci Med Sci 2005;60:109-13. [Crossref] [PubMed]
25. Sipiora ML, Murtaugh MA, Gregoire MB, et al. Bitter taste perception and severe vomiting in pregnancy. Physiol Behav 2000;69:259-67. [Crossref] [PubMed]
26. Duffy VB, Bartoshuk LM, Striegel-Moore R, et al. Taste changes across pregnancy. Ann N Y Acad Sci 1998;855:805-9. [Crossref] [PubMed]
27. Williams JA, Bartoshuk LM, Fillingim RB, et al. Exploring Ethnic Differences in Taste Perception. Chem Senses 2016;41:449-56. [Crossref] [PubMed]
28. Anseloni VC, Weng HR, Terayama R, et al. Age-dependency of analgesia elicited by intraoral sucrose in acute and persistent pain models. Pain 2002;97:93-103. [Crossref] [PubMed]
29. Blass E, Fitzgerald E, Kehoe P. Interactions between sucrose, pain and isolation distress. Pharmacol Biochem Behav 1987;26:483-9. [Crossref] [PubMed]
30. Blass EM, Fitzgerald E. Milk-induced analgesia and comforting in 10-day-old rats: opioid mediation. Pharmacol Biochem Behav 1988;29:9-13. [Crossref] [PubMed]
31. Lewkowski MD, Young SN, Ghosh S, et al. Effects of opioid blockade on the modulation of pain and mood by sweet taste and blood pressure in young adults. Pain 2008;135:75-81. [Crossref] [PubMed]
32. Peciña S. Opioid reward ‘liking’ and ‘wanting’ in the nucleus accumbens. Physiol Behav 2008;94:675-80. [Crossref] [PubMed]
33. Gebhart GF. Descending modulation of pain. Neurosci Biobehav Rev 2004;27:729-37. [Crossref] [PubMed]
34. Heinricher MM, Tavares I, Leith JL, et al. Descending control of nociception: Specificity, recruitment and plasticity. Brain Res Rev 2009;60:214-25. [Crossref] [PubMed]
35. Anseloni VC, Ren K, Dubner R, et al. A brainstem substrate for analgesia elicited by intraoral sucrose. Neuroscience 2005;133:231-43. [Crossref] [PubMed]
36. International Classification of Orofacial Pain, 1st edition (ICOP). Cephalalgia 2020;40:129-221.
37. Burning mouth syndrome. Available online: http://www.orofacialpain.org.uk/downloads/Orofacial%20pain%20patient%20leaflets/Burning_Mouth_Syndrome%20IASP%20fact%20sheet.pdf
38. Su N, Poon R, Liu C, et al. Pain reduction in burning mouth syndrome (BMS) may be associated with selective improvement of taste: a retrospective study. Oral Surg Oral Med Oral Pathol Oral Radiol 2020;129:461-7. [Crossref] [PubMed]
39. Grushka M, Ching V, Epstein J. Burning mouth syndrome. Adv Otorhinolaryngol 2006;63:278-87. [Crossref] [PubMed]
40. Nasri-Heir C, Shigdar D, Alnaas D, et al. Primary burning mouth syndrome: Literature review and preliminary findings suggesting possible association with pain modulation. Quintessence Int 2017;49:49-60. [PubMed]
41. Ship JA, Grushka M, Lipton JA, et al. Burning mouth syndrome: an update. J Am Dent Assoc 1995;126:842-53. [Crossref] [PubMed]
42. Zakrzewska J, Buchanan JA. Burning mouth syndrome. BMJ Clin Evid 2016;2016:1301. [PubMed]
43. Braud A, Descroix V, Ungeheuer MN, et al. Taste function assessed by electrogustometry in burning mouth syndrome: a case-control study. Oral Dis 2017;23:395-402. [Crossref] [PubMed]
44. Klasser GD, Grushka M, Su N. Burning Mouth Syndrome. Oral Maxillofac Surg Clin North Am 2016;28:381-96. [Crossref] [PubMed]
45. Eliav E, Kamran B, Schaham R, et al. Evidence of chorda tympani dysfunction in patients with burning mouth syndrome. J Am Dent Assoc 2007;138:628-33. [Crossref] [PubMed]
46. Blass EM, Shide DJ. Some comparisons among the calming and pain-relieving effects of sucrose, glucose, fructose and lactose in infant rats. Chem Senses 1994;19:239-49. [Crossref] [PubMed]
47. Shide DJ, Blass EM. Opioid mediation of odor preferences induced by sugar and fat in 6-day-old rats. Physiol Behav 1991;50:961-6. [Crossref] [PubMed]
48. Blass EM, Shah A. Pain-reducing properties of sucrose in human newborns. Chem Senses 1995;20:29-35. [Crossref] [PubMed]
49. Overgaard C, Knudsen A. Pain-relieving effect of sucrose in newborns during heel prick. Biol Neonate 1999;75:279-84. [Crossref] [PubMed]
50. Taddio A, Shah V, Katz J. Reduced infant response to a routine care procedure after sucrose analgesia. Pediatrics 2009;123:e425-9. [Crossref] [PubMed]
51. Schöbel N, Kyereme J, Minovi A, et al. Sweet taste and chorda tympani transection alter capsaicin-induced lingual pain perception in adult human subjects. Physiol Behav 2012;107:368-73. [Crossref] [PubMed]
52. Khan J, Anwer M, Noboru N, et al. Topical application in burning mouth syndrome. J Dent Sci 2019;14:352-7. [Crossref] [PubMed]
53. Grushka M, Epstein JB, Gorsky M. Burning mouth syndrome and other oral sensory disorders: a unifying hypothesis. Pain Res Manag 2003;8:133-5. [Crossref] [PubMed]
54. Formaker BK, Mott AE, Frank ME. The effects of topical anesthesia on oral burning in burning mouth syndrome. Ann N Y Acad Sci 1998;855:776-80. [Crossref] [PubMed]
55. Lamey PJ, Hobson RS, Orchardson R. Perception of stimulus size in patients with burning mouth syndrome. J Oral Pathol Med 1996;25:420-3. [Crossref] [PubMed]
56. Grushka M BL. Burning mouth syndrome and oral dysesthesias Can J Diag 2000;17:99-109.
57. Blakeslee AFaF. A.L. Our different taste worlds. J Hered 1932;23:97-107. [Crossref]
58. Fischer R. Gustation and Olfaction. Ohloff GaT, AF, editor. New York: Academic Press, 1971.
59. Bartoshuk LM. Sweetness: history, preference and genetic variability. Food Technol 1991;45:108-13.
60. Drewnowski A, Henderson SA, Shore AB, et al. Nontasters, tasters, and supertasters of 6-n-propylthiouracil (PROP) and hedonic response to sweet. Physiol Behav 1997;62:649-55. [Crossref] [PubMed]
61. Miller IJ Jr, Reedy FE Jr. Variations in human taste bud density and taste intensity perception. Physiol Behav 1990;47:1213-9. [Crossref] [PubMed]
62. Nasri-Heir C, Gomes J, Heir GM, et al. The role of sensory input of the chorda tympani nerve and the number of fungiform papillae in burning mouth syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;112:65-72. [Crossref] [PubMed]
63. Reed DR, Nanthakumar E, North M, et al. Localization of a gene for bitter-taste perception to human chromosome 5p15. Am J Hum Genet 1999;64:1478-80. [Crossref] [PubMed]
64. Bartoshuk LM, Duffy VB, Reed D, et al. Supertasting, earaches and head injury: genetics and pathology alter our taste worlds. Neurosci Biobehav Rev 1996;20:79-87. [Crossref] [PubMed]
65. Smith DV, Li CS. GABA-mediated corticofugal inhibition of taste-responsive neurons in the nucleus of the solitary tract. Brain Res 2000;858:408-15. [Crossref] [PubMed]
66. Davydenko V, Starchenko I. The Impact of the Acrylic Monomer on the Morphological Structure of Rat Lingual Mucosa. Georgian Med News 2018;146-51. [PubMed]
67. Marinone MG, Savoldi E. Chlorhexidine and taste. Influence of mouthwashes concentration and of rinsing time. Minerva Stomatol 2000;49:221-6. [PubMed]
68. Bartoshuk LM, Catalanotto F, Hoffman H, et al. J. Taste damage (otitis media, tonsillectomy and head and neck cancer), oral sensations and BMI. Physiol Behav 2012;107:516-26. [Crossref] [PubMed]
69. Rydzewski B, Pruszewicz A, Sulkowski WJ. Assessment of smell and taste in patients with allergic rhinitis. Acta Otolaryngol 2000;120:323-6. [Crossref] [PubMed]
70. Budimir V, Richter I, Andabak-Rogulj A, et al. Oral lichen planus - retrospective study of 563 Croatian patients. Med Oral Patol Oral Cir Bucal 2014;19:e255-60. [Crossref] [PubMed]
71. Rademacher WMH, Aziz Y, Hielema A, et al. Oral adverse effects of drugs: Taste disorders. Oral Dis 2020;26:213-23. [Crossref] [PubMed]
72. Femiano F, Scully C. Burning mouth syndrome (BMS): double blind controlled study of alpha-lipoic acid (thioctic acid) therapy. J Oral Pathol Med 2002;31:267-9. [Crossref] [PubMed]
73. Boyd I. Captopril-induced taste disturbance. Lancet 1993;342:304. [Crossref] [PubMed]
74. Levenson JL, Kennedy K. Dysosmia, dysgeusia, and nifedipine. Ann Intern Med 1985;102:135-6. [Crossref] [PubMed]
75. Berman JL. Dysosmia, dysgeusia, and diltiazem. Ann Intern Med 1985;102:717. [Crossref] [PubMed]
76. Juhlin L. Loss of taste and terbinafine. Lancet 1992;339:1483. [Crossref] [PubMed]
77. Henkin RI. Drug-induced taste and smell disorders. Incidence, mechanisms and management related primarily to treatment of sensory receptor dysfunction. Drug Saf 1994;11:318-77. [Crossref] [PubMed]
78. Bandyopadhyay U, Biswas K, Banerjee RK. Extrathyroidal actions of antithyroid thionamides. Toxicol Lett 2002;128:117-27. [Crossref] [PubMed]
79. Dileo MD, Amedee RG. Disorders of taste and smell. J La State Med Soc 1994;146:433-7. [PubMed]
80. Nishijima S, Yanase T, Tsuneki I, et al. Examination of the taste disorder associated with gynecological cancer chemotherapy. Gynecol Oncol 2013;131:674-8. [Crossref] [PubMed]
81. Sun A, Lin HP, Wang YP, et al. Significant association of deficiency of hemoglobin, iron and vitamin B12, high homocysteine level, and gastric parietal cell antibody positivity with atrophic glossitis. J Oral Pathol Med 2012;41:500-4. [Crossref] [PubMed]
82. Henkin RI, Hoetker JD. Deficient dietary intake of vitamin E in patients with taste and smell dysfunctions: is vitamin E a cofactor in taste bud and olfactory epithelium apoptosis and in stem cell maturation and development? Nutrition 2003;19:1013-21. [Crossref] [PubMed]
83. Risso DS, Kozlitina J, Sainz E, et al. Genetic Variation in the TAS2R38 Bitter Taste Receptor and Smoking Behaviors. PLoS One 2016;11:e0164157. [Crossref] [PubMed]
84. Thibodeau M, Pickering GJ. The role of taste in alcohol preference, consumption and risk behavior. Crit Rev Food Sci Nutr 2019;59:676-92. [Crossref] [PubMed]
85. Holland NJ, Bernstein JM. Bell's palsy. BMJ Clin Evid 2014;2014.
86. Vohra P, Rahman MSU, Subhada B, et al. Oral manifestation in leprosy: A cross-sectional study of 100 cases with literature review. J Family Med Prim Care 2019;8:3689-94. [Crossref] [PubMed]
87. Pedrosa MS, de Paiva M, Oliveira L, et al. Oral manifestations related to dengue fever: a systematic review of the literature. Aust Dent J 2017;62:404-11. [Crossref] [PubMed]
88. Abdullahi A, Candan SA, Abba MA, et al. Neurological and Musculoskeletal Features of COVID-19: A Systematic Review and Meta-Analysis. Front Neurol 2020;11:687. [Crossref] [PubMed]
89. Boscolo-Rizzo P, Polesel J, Spinato G, et al. Predominance of an altered sense of smell or taste among long-lasting symptoms in patients with mildly symptomatic COVID-19. Rhinology 2020;58:524-5. [PubMed]
90. Chen X, Laurent S, Onur OA, et al. A systematic review of neurological symptoms and complications of COVID-19. J Neurol 2021;268:392-402. [Crossref] [PubMed]
91. Reiter ER, Coelho DH, Kons ZA, et al. Subjective smell and taste changes during the COVID-19 pandemic: Short term recovery. Am J Otolaryngol 2020;41:102639. [Crossref] [PubMed]
92. Musialik J, Suchecka W, Klimacka-Nawrot E, et al. Taste and appetite disorders of chronic hepatitis C patients. Eur J Gastroenterol Hepatol 2012;24:1400-5. [Crossref] [PubMed]
93. Pavlidis P, Camara RJA, Kekes G, et al. Bilateral taste disorders in patients with Ramsay Hunt syndrome and Bell palsy. Ann Neurol 2018;83:807-15. [Crossref] [PubMed]
94. Soni NK, Chatterji P. Disturbance of taste in leprosy. J Laryngol Otol 1981;95:717-20. [Crossref] [PubMed]
95. Wang H, Zhou M, Brand J, et al. Inflammation and taste disorders: mechanisms in taste buds. Ann N Y Acad Sci 2009;1170:596-603. [Crossref] [PubMed]
96. Femiano F, Gombos F, Esposito V, et al. Burning mouth syndrome (BMS): evaluation of thyroid and taste. Med Oral Patol Oral Cir Bucal 2006;11:E22-5. [PubMed]
97. Mattes RD, Heller AD, Rivlin RS. Abnormalities in suprathreshold taste function in early hypothyroidism in humans. In: Meiselman HL, Rivlin RS. editors. Clinical Measurement of Taste and Smell. New York: Macmillan Publishing Co., 1986:467-86.
98. Mameli C, Cattaneo C, Lonoce L, et al. Associations Among Taste Perception, Food Neophobia and Preferences in Type 1 Diabetes Children and Adolescents: A Cross-Sectional Study. Nutrients 2019;11:3052. [Crossref] [PubMed]
99. DeVere R. Disorders of Taste and Smell. Continuum (Minneap Minn) 2017;23:421-46. [Crossref] [PubMed]
100. Clase CM, Ki V, Holden RM. Water-soluble vitamins in people with low glomerular filtration rate or on dialysis: a review. Semin Dial 2013;26:546-67. [Crossref] [PubMed]
101. Anuradha BR, Katta S, Kode VS, et al. Oral and salivary changes in patients with chronic kidney disease: A clinical and biochemical study. J Indian Soc Periodontol 2015;19:297-301. [Crossref] [PubMed]
102. Marinoski J, Bokor-Bratic M, Mitic I, et al. Oral mucosa and salivary findings in non-diabetic patients with chronic kidney disease. Arch Oral Biol 2019;102:205-11. [Crossref] [PubMed]
103. Loves R, Plenert E, Tomlinson V, et al. Changes in taste among pediatric patients with cancer and hematopoietic stem cell transplantation recipients. Qual Life Res 2019;28:2941-9. [Crossref] [PubMed]
104. Goto N, Yamamoto T, Kaneko M, et al. Primary pontine hemorrhage and gustatory disturbance: clinicoanatomic study. Stroke 1983;14:507-11. [Crossref] [PubMed]
105. Ibekwe TS, Fasunla AJ, Orimadegun AE. Systematic Review and Meta-analysis of Smell and Taste Disorders in COVID-19. OTO Open 2020;4:2473974X20957975.
106. Lee Y, Min P, Lee S, et al. Prevalence and Duration of Acute Loss of Smell or Taste in COVID-19 Patients. J Korean Med Sci 2020;35:e174. [Crossref] [PubMed]
107. Renzi G, Carboni A, Gasparini G, et al. Taste and olfactory disturbances after upper and middle third facial fractures: a preliminary study. Ann Plast Surg 2002;48:355-8. [Crossref] [PubMed]
108. Lehman CD, Bartoshuk LM, Catalanotto FC, et al. Effect of anesthesia of the chorda tympani nerve on taste perception in humans. Physiol Behav 1995;57:943-51. [Crossref] [PubMed]
109. Henkin RI, Christiansen RL. Taste localization on the tongue, palate, and pharynx of normal man. J Appl Physiol 1967;22:316-20. [Crossref] [PubMed]
110. Tomita H, Ikeda M, Okuda Y. Basis and practice of clinical taste examinations. Auris Nasus Larynx 1986;13:S1-15. [Crossref] [PubMed]
111. Albuquerque AFM, Soares ECS, de Barros Silva PG, et al. Clinical investigation of gustatory and neurosensory alterations following mandibular third molar surgery: an observational prospective study. Clin Oral Investig 2019;23:2941-9. [Crossref] [PubMed]
112. Anand R, Shankar DP, Manodh P, et al. Short-Term Evaluation of Gustatory Changes After Surgical Removal of Mandibular Third Molar-A Prospective Randomized Control Trial. J Oral Maxillofac Surg 2018;76:258-66. [Crossref] [PubMed]
113. Morton RP, Hay KD, Goldsmith DB, et al. Patterns of sensory recovery in the lingual nerve after surgical trauma. N Z Dent J 2005;101:53-7. [PubMed]
114. Maas SM, Kadouch DJ, Masselink AC, et al. Taste and speech following surgical tongue reduction in children with Beckwith-Wiedemann syndrome. J Craniomaxillofac Surg 2016;44:659-63. [Crossref] [PubMed]
115. Bartoshuk LM, Gent J, Catalanotto FA, et al. Clinical evaluation of taste. Am J Otolaryngol 1983;4:257-60. [Crossref] [PubMed]
116. Benoliel R, Birman N, Eliav E, et al. The International Classification of Headache Disorders: accurate diagnosis of orofacial pain? Cephalalgia 2008;28:752-62. [Crossref] [PubMed]
117. Just T, Steiner S, Pau HW. Oral pain perception and taste in burning mouth syndrome. J Oral Pathol Med 2010;39:22-7. [Crossref] [PubMed]
118. Imura H, Shimada M, Yamazaki Y, et al. Characteristic changes of saliva and taste in burning mouth syndrome patients. J Oral Pathol Med 2016;45:231-6. [Crossref] [PubMed]
119. McConnell RJ, Menendez CE, Smith FR, et al. Defects of taste and smell in patients with hypothyroidism. Am J Med 1975;59:354-64. [Crossref] [PubMed]
120. Hovan AJ, Williams PM, Stevenson-Moore P, et al. A systematic review of dysgeusia induced by cancer therapies. Support Care Cancer 2010;18:1081-7. [Crossref] [PubMed]
121. Eliav E, Gracely RH, Nahlieli O, et al. Quantitative sensory testing in trigeminal nerve damage assessment. J Orofac Pain 2004;18:339-44. [PubMed]
122. Zuniga JR, Chen N, Phillips CL. Chemosensory and somatosensory regeneration after lingual nerve repair in humans. J Oral Maxillofac Surg 1997;55:2-13; discussion 14. [Crossref] [PubMed]
123. Hillerup S, Hjorting-Hansen E, Reumert T. Repair of the lingual nerve after iatrogenic injury: a follow-up study of return of sensation and taste. J Oral Maxillofac Surg 1994;52:1028-31. [Crossref] [PubMed]
124. Chen N, Zhao SF, Gu ZY, et al. Experimental study of the fungiform papilla and taste bud regeneration following microsurgical repair of lingual nerve in rat. Shanghai Kou Qiang Yi Xue 2004;13:519-22. [PubMed]
125. Kumbargere Nagraj S, George RP, Shetty N, et al. Interventions for managing taste disturbances. Cochrane Database Syst Rev 2017;12:CD010470. [PubMed]
126. Michelson M, Veitz-Keenan A. Taste disturbances - are there any effective treatments? Evid Based Dent 2018;19:60-1. [Crossref] [PubMed]
127. Henkin RI, Schultz M, Minnick-Poppe L. Intranasal theophylline treatment of hyposmia and hypogeusia: a pilot study. Arch Otolaryngol Head Neck Surg 2012;138:1064-70. [Crossref] [PubMed]