今日の臨床サポート

抗癌剤による味覚障害に対する治療

著者: 藤山理恵 長崎大学 総合歯科臨床教育学

監修: 佐治重衡 福島県立医科大学

著者校正/監修レビュー済:2021/04/07
参考ガイドライン:
  1. 日本臨床栄養学会亜鉛欠乏症の診療指針2018
  1. 厚生労働省:重篤副作用疾患別対応マニュアル 薬物性味覚障害
患者向け説明資料

概要・推奨   

  1. 診断には味覚機能検査・血清亜鉛値測定・唾液量測定を行うことも試みる価値がある(推奨度2)
  1. 味覚は温度感受性もあることから口腔内で氷による冷刺激をすることは試みる価値がある(推奨度2)
  1. サクソンテストにより口腔乾燥症の診断がある場合 唾液腺のマッサージを行うことも試みる価値がある(推奨度2)
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
藤山理恵 : 研究費・助成金など(独立行政法人日本学術振興会基盤研究(C))[2021年]
監修:佐治重衡 : 講演料(イーライリリー,中外製薬,第一三共,ファイザー,協和キリン,アストラゼネカ),研究費・助成金など(中外製薬,第一三共),奨学(奨励)寄付など(中外製薬)[2021年]

改訂のポイント:
  1. 参考ガイドラインに「亜鉛欠乏症の診療指針2018」「重篤副作用疾患別対応マニュアル 薬物性味覚障害」を加えた。
  1. 味覚障害の症状による分類に関する表を加えた。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 味覚障害は癌治療(放射線療法・化学療法・併用)に共通する口腔内の合併症の1つであり、QOL低下につながる。(参考文献:[1][2][3][4][5][6][7][8]
  1. 化学療法のみによる味覚障害の有病率は56%である。(参考文献:[1]
  1. 化学療法開始後、数日から1週間程度で発症することが多い。
  1. 味覚障害と嗅覚障害は密接な関係がある。
  1. 味覚障害の症状は、味覚感度の低下または上昇や自発性の不快な金属味・苦味など多様である。
  1. 味覚障害のほか、口腔乾燥症・口腔内の炎症(舌炎・口内炎)を伴うことも多い。
  1. 抗癌剤による味覚障害には、特異的な効果的治療法がないのが現状である。血清亜鉛値低下(80μg/dl未満)の場合は、亜鉛内服治療を行う。(参考文献:[1][2][3][4][5][6][7][8][9]
  1. 化学療法終了後3~4週で味覚の改善がみられることもあり、1年ほどで味覚障害は自然治癒する可能性がある。
 
  1. 診断には味覚機能検査・血清亜鉛値測定・唾液量測定を行うことも試みる価値がある(推奨度2S)
  1. 化学療法による味覚障害の有病率は56%である。味覚障害の症状は、味覚感度の低下や自発性の不快な金属味・苦味など多様である。味覚障害のほか口腔乾燥症・口腔内の炎症(舌炎・口内炎)を伴うことも多い。嗅覚障害とは密接な関係があり、味覚は正常でも嗅覚障害により自覚的味覚障害を訴えることもある。また精神的ストレスによる味覚障害など原因も多様である。化学療法終了後3~4週で味覚の改善がみられることもあり、1年ほどで味覚障害は自然治癒する可能性があるが、抗癌剤による味覚障害は患者のQOL低下や食欲不振による栄養状態の悪化、さらにはADLの低下を招くこともあり、味覚障害の改善は大切である。
  1. 味覚障害の病態には不明な点が多く、そのため確立された治療法がないのが現状である(参考文献:[8])。例えば治療の1つと考えられている亜鉛製剤内服の有効性について、有効でないという結果もある。しかし抗癌剤治療中に栄養状態を良好に保つうえで、味覚障害を訴える患者の抗癌剤治療を少しでも有効にするために、必要に応じて行うことも試みる価値がある。
  1. 味覚機能検査結果に問題がある場合には、以下の治療法も試みる価値がある。
  1. 亜鉛製剤の内服(血清亜鉛値が低い場合(80μg/dl未満))
    ただし銅欠乏(血清銅低値)に注意する必要がある。
  1. 末梢神経治療薬の内服
  1. 嗅覚に問題がない場合、好みの香りの食事をすることも、味覚障害による食欲不振の改善につながる。
問診・診察のポイント  
  1. 発症時期と状況の確認:問診――化学療法開始時期との関連、全身疾患(腎障害・肝障害・糖尿病・消化器疾患・ビタミン欠乏症・甲状腺機能障害)・歯科治療(金属などの補綴物の装着など)・心理的ストレスのエピソードなど
  1. 口腔合併症の確認:問診――口腔内の疼痛の有無、食物の刺激による疼痛の有無、診察――口内炎・舌炎・口腔乾燥・舌苔の視診
  1. 嗅覚障害の有無:問診――食事中などの匂いの変化の有無
  1. 食欲低下の有無:問診――体重減少・食欲不振の有無、食事量減少の有無

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

著者: Allan J Hovan, P Michele Williams, Peter Stevenson-Moore, Yula B Wahlin, Kirsten E O Ohrn, Linda S Elting, Fred K L Spijkervet, Michael T Brennan, Dysgeusia Section, Oral Care Study Group, Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO)
雑誌名: Support Care Cancer. 2010 Aug;18(8):1081-7. doi: 10.1007/s00520-010-0902-1. Epub 2010 May 22.
Abstract/Text PURPOSE: The purpose was to review relevant scientific papers written since 1989 which focused on the prevalence and management of dysgeusia as an oral side effect of cancer treatment.
METHODS: Our literature search was limited to English language papers published between 1990 and 2008. A total of 30 papers were reviewed; the results of 26 of these papers were included in the present systematic review. A structured assessment form was used by two reviewers for each paper. Studies were weighted as to the quality of the study design, and treatment recommendations were based on the relative strength of each paper.
RESULTS: A wide range in reported prevalence of dysgeusia was identified with the weighted prevalence from 56-76%, depending on the type of cancer treatment. Attempts to prevent dysgeusia through the prophylactic use of zinc sulfate or amifostine have been of limited benefit. Nutritional counseling may be helpful to some patients in minimizing the symptoms of dysgeusia.
CONCLUSIONS: Dysgeusia is a common oral side effect of cancer therapy (radiotherapy, chemotherapy, or combined modality therapy) and often impacts negatively on quality of life. From the current literature, there does not appear to be a predictable way of preventing or treating dysgeusia.

PMID 20495984  Support Care Cancer. 2010 Aug;18(8):1081-7. doi: 10.100・・・
著者: Jae Hee Hong, Pinar Omur-Ozbek, Brian T Stanek, Andrea M Dietrich, Susan E Duncan, Yong Woo Lee, Glenn Lesser
雑誌名: J Support Oncol. 2009 Mar-Apr;7(2):58-65.
Abstract/Text Taste and odor abnormalities are major daily concerns for patients with cancer. This review summarizes the common taste and odor disorders of cancer patients and provides insight into their possible causes. Cancer and its therapy, including chemotherapy and radiotherapy, may directly alter and damage taste and odor perception.These alterations affect the daily quality of life of these patients and may lead to patient malnutrition and, in severe cases, significant morbidity. Cancer patients experience decreases in sensitivity to taste and odor, as well as unpleasant metallic and bitter sensations. Complaints relating to taste and odor are not usually addressed, as few, if any, effective interventions are available for these problems. Understanding the types and causes of taste and odor dysfunctions will enable researchers and physicians to develop treatments for these conditions and thereby improve patient quality of life.

PMID 19408458  J Support Oncol. 2009 Mar-Apr;7(2):58-65.
著者: P Beale, I Judson, A O'Donnell, J Trigo, C Rees, F Raynaud, A Turner, L Simmons, L Etterley
雑誌名: Br J Cancer. 2003 Apr 7;88(7):1128-34. doi: 10.1038/sj.bjc.6600854.
Abstract/Text AMD473 is a novel sterically hindered platinum cytotoxic with demonstrated ability to overcome acquired resistance to cisplatin in vitro and in human tumour xenografts. A single-agent dose escalating Phase I study was performed. AMD473 was initially administered intravenously as a 1 h infusion every 21 days to patients with advanced solid tumours. In total, 42 patients received a total of 147 cycles (median 3, range 1-8) of treatment at doses of 12, 24, 48, 96, 110, 120, 130, and 150 mg m(-2). Dosing intervals of 21 and 28 days were explored at the recommended dose. Neutropenia and thrombocytopenia proved dose limiting. Other toxicities included moderate nausea, vomiting, anorexia, and a transient metallic taste. There was no significant alopecia. The maximum tolerated dose was 150 mg m(-2). Plasma pharmacokinetics were linear. Two patients with heavily pretreated ovarian cancer showed partial response. Five patients (mesothelioma, ovary, nonsmall cell lung, and melanoma) showed prolonged stable disease. AMD473 demonstrates encouraging activity in patients, including those with prior platinum exposure. Toxicity is predictable with linear pharmacokinetics, as was predicted by preclinical studies. A dose of 120 mg m(-2) every 21 days is recommended for Phase II evaluation although there is evidence that chemo-naive patients and those of good performance status may tolerate a higher dose.

PMID 12671715  Br J Cancer. 2003 Apr 7;88(7):1128-34. doi: 10.1038/sj.・・・
著者: G Macquart-Moulin, P Viens, T Palangié, M L Bouscary, T Delozier, H Roché, M Janvier, M Fabbro, J P Moatti
雑誌名: J Clin Oncol. 2000 Feb;18(4):754-64.
Abstract/Text PURPOSE: This study was designed to investigate the quality of life (QOL) of patients enrolled onto the High-Dose Chemotherapy for Breast Cancer Study Group trial (PEGASE 02), a French pilot multicenter trial of the treatment of inflammatory breast cancer (IBC) aimed at evaluating (1) toxicity and feasibility of sequential high-dose chemotherapy (HDC) with recombinant human granulocyte colony-stimulating factor (filgrastim) and stem-cell support and (2) response to HDC in terms of pathologic response and survival.
PATIENTS AND METHODS: QOL measures were performed at inclusion and four times subsequently up to 1 year using an ad hoc side-effect questionnaire (19 physical symptoms) and the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30).
RESULTS: Of the 95 patients entered, the overall QOL questionnaire completion compliance was 75.6%. During cycle 3 of HDC, the number of symptoms was high (mean +/- SD QOL score, 10 +/- 3), with fatigue, hair loss, appetite loss, nausea, change in taste, vomiting, fever, and weight loss reported by more than 60% of patients. Toxicity and distress associated with HDC were reflected in the decline of four EORTC QLQ-C30 scores: global QOL (P =.001), and physical, role, and social functioning (P <.001 for all statistics). However, QOL deterioration disappeared after treatment completion, except for physical functioning (P =.025). One year after inclusion, most QOL scores returned to baseline, and both emotional functioning and global QOL scores were even higher than baseline (P =.030 and P =.009, respectively).
CONCLUSION: If it is confirmed that improvements in pathologic response rates with HDC effectively translate into increased probabilities of survival for IBC patients, adoption of such treatment as PEGASE 02 will not involve crucial choices between length of life and QOL and should not be delayed for QOL arguments.

PMID 10673516  J Clin Oncol. 2000 Feb;18(4):754-64.
著者: Roberto Maisano, Marzia Mare, Maria Zavettieri, Nicola Caristi, Mario Mesiti, Claudio Scisca, Francesco La Torre
雑誌名: Anticancer Res. 2003 Mar-Apr;23(2C):1923-6.
Abstract/Text BACKGROUND: Docetaxel is a very active drug against breast cancer, but at the standard dose causes severe myelosuppression. In order to reduce the toxicity while maintaining the activity, weekly docetaxel administration was tested.
PATIENTS AND METHODS: We enrolled 30 patients with metastatic breast cancer, who had been treated with intravenous infusion of weekly docetaxel 35 mg/m2 in 100 ml of normal saline over 30 minutes for six weeks, followed by two weeks' rest from docetaxel therapy (one cycle).
RESULTS: The overall response rate was 33% (95% CI +/- 16.8%) and the estimated time to progression was 8 months. Acute toxicity was mild. Nail loss, excessive tearing and dysgeusia worsened the quality of life of the patients.
CONCLUSION: Weekly docetaxel is an active schedule for treating metastatic breast cancer patients, particularly the elderly and those unsuited to anthracycline-based regimens.

PMID 12820480  Anticancer Res. 2003 Mar-Apr;23(2C):1923-6.
著者: Laurel Lyckholm, Steven P Heddinger, Gwendolyn Parker, Patrick J Coyne, Viswanathan Ramakrishnan, Thomas J Smith, Robert I Henkin
雑誌名: J Pain Palliat Care Pharmacother. 2012 Jun;26(2):111-4. doi: 10.3109/15360288.2012.676618.
Abstract/Text Abnormalities in taste and smell are commonly reported in patients receiving chemotherapy and may hinder appetite, dietary intake, nutritional well-being, and quality of life. Oral zinc has been used to treat taste and smell abnormalities in several altered physiologic states, including renal failure, liver disease, head trauma, and pregnancy, with varying results. The authors conducted a double-blinded, placebo-controlled randomized clinic trial over 3 months. Eligible patients were those taking chemotherapy that had alterations in taste and/or smell. The measurement of the primary end point, improvement in altered taste and smell, was made using a 0-100 scale (100 describing no loss or distortion in taste and smell, and 0 describing the worst distortion or loss of taste and smell). Twenty-nine subjects were enrolled in each treatment group, of whom 31 were white, 26 African American, and 1 Native American. Forty-one patients were female. A wide range of cancer types was represented, with breast the most common (21 patients). The zinc dose was 220 mg orally twice daily (equivalent of 50 mg elemental zinc twice daily). There was no statistically significant improvement in loss or distortion of taste or smell with the addition of zinc. There was a trend toward improvement over time in all groups, except in the zinc group where there was a nonsignificant worsening in loss of smell over time. Zinc at standard doses did not provide significant benefit to taste or smell in patients receiving chemotherapy.

PMID 22764846  J Pain Palliat Care Pharmacother. 2012 Jun;26(2):111-4.・・・
著者: Shota Nishijima, Toru Yanase, Ikunosuke Tsuneki, Masaki Tamura, Takumi Kurabayashi
雑誌名: Gynecol Oncol. 2013 Dec;131(3):674-8. doi: 10.1016/j.ygyno.2013.09.015. Epub 2013 Sep 20.
Abstract/Text OBJECTIVE: Taste disturbance is known to occur as one of the adverse events associated with chemotherapy for gynecological cancer, but few studies have attempted to assess it in practical terms. Therefore, a range of taste tests was performed in gynecological cancer patients.
METHODS: The patients were 23 women with gynecological cancer being treated with anticancer agents. Subjective symptoms of altered taste were classified, and objective findings were obtained with the following four gustatory tests: serum trace element (zinc, copper, iron) levels, tongue cultures, electrogustometry, and the filter paper disc tests.
RESULTS: Of the 23 subjects, 11 perceived taste disturbances. The serum zinc level was consistently below the lower limit of normal. On tongue cultures, indigenous bacteria were seen in all patients during the entire treatment period. Electrogustometry revealed a tendency for the development of hypogeusia in the chorda tympani nerve field. Conversely, hypergeusia tended to develop gradually in the greater petrosal nerve field. The filter paper disc test revealed a tendency for the development of hypergeusia for sweetness, saltiness, and sourness in the chorda tympani nerve field. Hypogeusia for bitterness tended to develop with increasing number of chemotherapy cycles. The glossopharyngeal nerve field exhibited the same tendencies as observed in the chorda tympani nerve field. In the greater petrosal nerve field, there was a tendency for the development of hypergeusia for sweetness, sourness, and bitterness.
CONCLUSIONS: Abnormal test results were seen in half of patients after cancer chemotherapy.

© 2013.
PMID 24060414  Gynecol Oncol. 2013 Dec;131(3):674-8. doi: 10.1016/j.yg・・・
著者: Olga Sevryugin, Popi Kasvis, MariaLuisa Vigano, Antonio Vigano
雑誌名: Support Care Cancer. 2021 Jan;29(1):49-66. doi: 10.1007/s00520-020-05609-4. Epub 2020 Jul 30.
Abstract/Text PURPOSE: Taste and smell disturbances in patients affected by cancer are very common, but often under-recognized symptoms. If not addressed properly, they may impact nutritional status, food enjoyment, and quality of life. Treatment tools available for clinicians to manage chemosensory alterations are limited and are often based on personal clinical experiences. The aim of this study was to assess current oncological and palliative care literature through a scoping review, in order to identify available treatments for taste and smell alterations in cancer patients.
METHODS: Medline, Embase, CINAHL, ProQuest Dissertations and Theses, and Google Scholar were searched from inception until January 2020, with subject headings relevant to the domains of chemosensory alterations, palliative, and cancer care. A total of 10,718 English and French language publications were reviewed, yielding 43 articles on the researched topic.
RESULTS: The heterogeneity of selected articles led to difficulties in interpretation and analysis of the available evidence. Included publications differed in study design, population sample, anticancer treatments, and measures of assessment for taste and smell disturbances. A broad variety of treatment options were described including zinc and polaprezinc, radio-protectors, vitamins and supplements, anti-xerostomia agents, active swallowing exercises, nutritional interventions, delta-9-tetrahydrocannabinol, and photobiomodulation.
CONCLUSION: This scoping review identifies the current state of knowledge regarding chemosensory alterations within supportive cancer care. Despite not reaching firm conclusions, this article offers therapeutic venues to further explore in larger and more methodologically sound studies.

PMID 32734392  Support Care Cancer. 2021 Jan;29(1):49-66. doi: 10.1007・・・
著者: C Ripamonti, F Fulfaro
雑誌名: J Pain Symptom Manage. 1998 Dec;16(6):349-51.
Abstract/Text
PMID 9879158  J Pain Symptom Manage. 1998 Dec;16(6):349-51.
著者: Chiyoko Hakuta, Chisato Mori, Masayuki Ueno, Kayoko Shinada, Yoko Kawaguchi
雑誌名: Gerodontology. 2009 Dec;26(4):250-8. doi: 10.1111/j.1741-2358.2008.00269.x. Epub 2009 Jun 25.
Abstract/Text OBJECTIVES: The purpose of this study was to provide an oral function promotion programme for the independent elderly and evaluate the changes in oral health status and oral function. Background: Few studies have scientifically analysed and evaluated the effectiveness of oral function promotion programmes provided for the independent elderly.
MATERIALS AND METHODS: The subjects were independent elderly females (mean age: 74.6 +/- 6.3) recruited from senior citizens' centres in Tokyo. The intervention group (n = 79) received a 3-month oral function promotion programme, which included facial muscle and tongue exercises and salivary gland massages. The control group (n = 62) did not receive this programme.
RESULTS: In the intervention group, the tongue coating scores decreased and the organoleptic score of oral malodour fell. The amount of food debris in the oral cavity decreased and the tongue dryness improved. Furthermore, the salivary flow rate increased. The length of time for maintaining the tongue in the forward position increased from 11.2 s to 18.7 s, and the number of times for moving the tip of the tongue in a clockwise circular motion, counter-clockwise circular motion and side-to-side motion within 30 s, increased from 14.5 to 20.6, 14.5 to 20.2, and 17.2 to 23.3 respectively. The number of times for movement of the lips significantly improved from 23.0 to 28.8 and the pronunciation of words was observed to be clearer.
CONCLUSION: An oral function promotion programme was effective in improving the oral health status and oral function of an independent elderly population.

PMID 19555360  Gerodontology. 2009 Dec;26(4):250-8. doi: 10.1111/j.174・・・
著者: Akira Shiozawa
雑誌名: Nihon Yakurigaku Zasshi. 2002 Oct;120(4):253-8.
Abstract/Text Cevimeline hydrochloride hydrate is a muscarinic receptor agonist with a chemical structure of a quinuclidine. Intraduodenal administration of cevimeline hydrochloride hydrate dose-dependently increased salivary secretion in normal mice and rats, two strains of autoimmune disease mice, and X-irradiated rats. The clinical efficacy of the cevimeline hydrochlide hydrate at 30 mg t.i.d. during 4 weeks has been demonstrated in double blind comparative study with placebo. In addition, its treatments in 52 weeks have increased salivary flow and improved subjective and objective symptoms of patients with xerostomia in Sjögren's syndrome.

PMID 12425151  Nihon Yakurigaku Zasshi. 2002 Oct;120(4):253-8.
著者: Rie Fujiyama, Shingo Ishitobi, Keiko Honda, Yukio Okada, Kumiko Oi, Kazuo Toda
雑誌名: Odontology. 2010 Feb;98(1):82-4. doi: 10.1007/s10266-009-0110-y. Epub 2010 Feb 16.
Abstract/Text Dysgeusia causes a decrease in appetite, and it is one of the major factors in undernutrition. Dysgeusia is elicited by numerous causes, and in many cases it is still difficult to treat the various symptoms complained of by patients. We herein report a case in which dysgeusia was improved by transient cooling of the mouth.

PMID 20155512  Odontology. 2010 Feb;98(1):82-4. doi: 10.1007/s10266-00・・・
著者: Rie Fujiyama, Kazuo Toda
雑誌名: Odontology. 2017 Jul;105(3):275-282. doi: 10.1007/s10266-016-0263-4. Epub 2016 Aug 22.
Abstract/Text Thermal modulation of signaling pathways leads to excitation of taste receptor cells, but the underlying mechanisms remain unclear. Furthermore, it has long been known that there are contrast effects in various senses. In this study, we investigated cold-taste contrast and the relationship between taste and somatosensation. We lowered intraoral temperature using cold stimulus as a pretreatment, then returned to normal temperature in 249 healthy subjects, before administering room temperature taste-stimulating solutions to investigate changes in sensitivity to the four basic tastes (Sweet, Salt, Sour, and Bitter). Statistical comparisons of taste recognition thresholds before and after cold stimulus showed increased taste sensitivity for all four basic tastes. After categorizing different levels of pre-cold stimulus taste sensitivity into groups and comparing changes in sensitivity to the four basic tastes before and after stimulus, we found that the lower the sensitivity to the four basic tastes, the greater the increase in sensitivity induced by cold stimulus. These findings suggest that taste and low temperature send afferent signals which cause interaction in the afferent pathways between the peripheral and central nervous systems. Cold stimulus may offer one possible treatment strategy for dysgeusia.

PMID 27550339  Odontology. 2017 Jul;105(3):275-282. doi: 10.1007/s1026・・・

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