Top

Published in:

Open Access 01-12-2013 | Research article

Headache and mechanical sensitization of human pericranial muscles after repeated intake of monosodium glutamate (MSG)

Authors: Akiko Shimada, Brian E Cairns, Nynne Vad, Kathrine Ulriksen, Anne Marie Lynge Pedersen, Peter Svensson, Lene Baad-Hansen

Published in: The Journal of Headache and Pain | Issue 1/2013

Abstract

Background

A single intake of monosodium glutamate (MSG) may cause headache and increased muscle sensitivity. We conducted a double-blinded, placebo-controlled, crossover study to examine the effect of repeated MSG intake on spontaneous pain, mechanical sensitivity of masticatory muscles, side effects, and blood pressure.

Methods

Fourteen healthy subjects participated in 5 daily sessions for one week of MSG intake (150 mg/kg) or placebo (24 mg/kg NaCl) (randomized, double-blinded). Spontaneous pain, pressure pain thresholds and tolerance levels for the masseter and temporalis muscles, side effects, and blood pressure were evaluated before and 15, 30, and 50 min after MSG intake. Whole saliva samples were taken before and 30 min after MSG intake to assess glutamate concentrations.

Results

Headache occurred in 8/14 subjects during MSG and 2/14 during placebo (P = 0.041). Salivary glutamate concentrations on Day 5 were elevated significantly (P < 0.05). Pressure pain thresholds in masseter muscle were reduced by MSG on Day 2 and 5 (P < 0.05). Blood pressure was significantly elevated after MSG (P < 0.040).

Conclusion

In conclusion, MSG induced mechanical sensitization in masseter muscle and adverse effects such as headache and short-lasting blood pressure elevation for which tolerance did not develop over 5 days of MSG intake.

Available only for authorised users

Cairns BE: Pathophysiology of TMD pain - basic mechanisms and their implications for pharmacotherapy. J Oral Rehabil 2010, 37: 391–410. 10.1111/j.1365-2842.2010.02074.xPubMedCrossRef

LeResche L, Drangsholt M: Epidemiology of orofacial pain: prevalence, incidence, and risk factors. In Orofacial pain: from basic science to clinical management. Edited by: Sessle BJ, Lavigne GJ, Lund JP, Dubner R. Quintessence Books, Illinois; 2008:13–18.

Lobbezoo F, Drangsholt MT, Peck C, Sato H, Kopp S, Svensson P: Topical review: new insights into the pathology and diagnosis of disorders of the temporomandibular joint. J Orofac Pain 2004, 18: 181–191.PubMed

Glaros AG: Temporomandibular disorders and facial pain: a psychophysiological perspective. Appl Psychophysiol Biofeedback 2008, 33: 161–171. 10.1007/s10484-008-9059-9PubMedCrossRef

Hutchins MO, Skjonsby HS: Microtrauma to rat superficial masseter muscles following lengthening contractions. J Dent Res 1990, 69: 1580–1585. 10.1177/00220345900690090901PubMedCrossRef

Suvinen TI, Reade PC, Kemppainen P, Könönen M, Dworkin SF: Review of aetiological concepts of temporomandibular pain disorders: towards a biopsychosocial model for integration of physical disorder factors with psychological and psychosocial illness impact factors. Eur J Pain 2005, 9: 613–633. 10.1016/j.ejpain.2005.01.012PubMedCrossRef

Manfredini D, Lobbezoo F: Relationship between bruxism and temporomandibular disorders: a systematic review of literature from 1998 to 2008. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010, 109: e26-e50. 10.1016/j.tripleo.2010.02.013PubMedCrossRef

Svensson P, Jadidi F, Arima T, Baad-Hansen L, Sessle BJ: Relationships between craniofacial pain and bruxism. J Oral Rehabil 2008, 35: 524–547. 10.1111/j.1365-2842.2008.01852.xPubMedCrossRef

Raphael KG, Marbach JJ, Touger-Decker R: Dietary fiber intake in patients with myofascial face pain. J Orofac Pain 2002, 16: 39–47.PubMed

10.

Freeman M: Reconsidering the effects of monosodium glutamate: a literature review. J Am Acad Nurse Pract 2006, 18: 482–486. 10.1111/j.1745-7599.2006.00160.xPubMedCrossRef

11.

Geha RS, Beiser A, Ren C, Patterson R, Greenberger PA, Grammer LC, Ditto AM, Harris KE, Shaughnessy MA, Yarnold PR, Corren J, Saxon A: Review of alleged reaction to monosodium glutamate and outcome of a multicenter double-blind placebo-controlled study. J Nutr 2000,130(4S Suppl):58S-62S.

12.

Nelson LM, Matkin C, Longstreth WTJ, McGuire V: Population-based case-control study of amyotrophic lateral sclerosis in western Washington State. II. Diet. Am J Epidemiol 2000, 151: 164–173. 10.1093/oxfordjournals.aje.a010184PubMedCrossRef

13.

Baad-Hansen L, Cairns BE, Ernberg M, Svensson P: Effect of systemic monosodium glutamate (MSG) on headache and pericranial muscle sensitivity. Cephalalgia 2010, 30: 68–76. 10.1111/j.1468-2982.2009.01881.xPubMed

14.

Graham TE, Sgro V, Friars D, Gibala MJ: Glutamate ingestion: the plasma and muscle free amino acid pools of resting humans. Am J Physiol Endocrinol Metab 2000, 278: E83-E89.PubMed

15.

Cairns BE, Dong XD, Mann MK, Svensson P, Sessle BJ, Arendt-Nielsen L, McErlane KM: Systemic administration of monosodium glutamate elevates intramuscular glutamate levels and sensitizes rat masseter muscle afferent fibers. Pain 2007, 132: 33–41. 10.1016/j.pain.2007.01.023PubMedCentralPubMedCrossRef

16.

Castrillon EE, Ernberg M, Cairns BE, Wang K, Sessle BJ, Arendt-Nielsen L, Svensson P: Interstitial glutamate concentration is elevated in the masseter muscle of myofascial temporomandibular disorder patients. J Orofac Pain 2010, 24: 350–360.PubMed

17.

Pedersen AM, Reibel J, Nauntofte B: Primary Sjögren’s syndrome (pSS): subjective symptoms and salivary findings. J Oral Pathol Med 1999, 28: 303–311. 10.1111/j.1600-0714.1999.tb02045.xPubMedCrossRef

18.

Bardow A, Pedersen AM, Nauntofte B: Saliva. In Clinical oral physiology. Edited by: Miles TS, Nauntofte B, Svensson P. Quintessence Publishing Co. Ltd., Copenhagen; 2004:17–51.

19.

Svensson P, Cairns BE, Wang K, Arendt-Nielsen L: Injection of nerve growth factor into human masseter muscle evokes long-lasting mechanical allodynia and hyperalgesia. Pain 2003, 104: 241–247. 10.1016/S0304-3959(03)00012-5PubMedCrossRef

20.

Scinska-Bienkowska A, Wrobel E, Turzynska D, Bidzinski A, Jezewska E, Sienkiewicz-Jarosz H, Golembiowska K, Kostowski W, Kukwa A, Plaznik A, Bienkowski P: Glutamate concentration in whole saliva and taste responses to monosodium glutamate in humans. Nutr Neurosci 2006, 9: 25–31. 10.1080/10284150600621964PubMedCrossRef

21.

Gazerani P, Au S, Dong X, Kumar U, Arendt-Nielsen L, Cairns BE: Botulinum neurotoxin type A (BoNTA) decreases the mechanical sensitivity of nociceptors and inhibits neurogenic vasodilation in a craniofacial muscle targeted for migraine prophylaxis. Pain 2010, 151: 606–616. 10.1016/j.pain.2010.07.029PubMedCrossRef

22.

Dong XD, Mann M, Kumar U, Svensson P, Arendt-Nielsen L, Hu JW, Sessle BJ, Cairns BE: Sex-related differences in NMDA-evoked rat masseter muscle afferent discharge result from estrogen-mediated modulation of peripheral NMDA receptor activity. Neuroscience 2007, 146: 822–832. 10.1016/j.neuroscience.2007.01.051PubMedCentralPubMedCrossRef

23.

Dong XD, Mann MK, Sessle BJ, Arendt-Nielsen L, Svensson P, Cairns BE: Sensitivity of rat temporalis muscle afferent fibers to peripheral N-methyl-D-aspartate receptor activation. Neuroscience 2006, 141: 939–945. 10.1016/j.neuroscience.2006.04.024PubMedCrossRef

24.

Castrillon EE, Cairns BE, Wang K, Arendt-Nielsen L, Svensson P: Comparison of glutamate-evoked pain between the temporalis and masseter muscles in men and women. Pain 2012, 153: 823–829. 10.1016/j.pain.2012.01.003PubMedCrossRef

25.

Shi Z, Yuan B, Taylor AW, Dai Y, Pan X, Gill TK, Wittert GA: Monosodium glutamate is related to a higher increase in blood pressure over 5 years: findings from the Jiangsu Nutrition Study of Chinese adults. J Hypertens 2011, 29: 846–853. 10.1097/HJH.0b013e328344da8ePubMedCrossRef

26.

Bulpitt CJ, Dollery CT: Change in symptoms of hypertensive patients after referral to hospital clinic. Br Heart Journal 1976, 38: 121–128. 10.1136/hrt.38.2.121CrossRef

27.

Cooper WD, Glover DR, Hormbrey JM, Kimber GR: Headache and blood pressure: evidence of a close relationship. J Human Hypertension 1989, 3: 41–44.

28.

Waters WE: Headache and blood pressure in the community. Br Med J 1971, 1: 142–143. 10.1136/bmj.1.5741.142PubMedCentralPubMedCrossRef

29.

Gudmundsson LS, Thorgeirsson G, Sigfusson N, Sigvaldason H, Johannsson M: Migraine patients have lower systolic but higher diastolic blood pressure compared with controls in a population-based study of 21537 subjects. The Reykjavik Study Cephalalgia 2006, 26: 436–444. 10.1111/j.1468-2982.2005.01057.xPubMedCrossRef

30.

Benseñor IJM, Lotufo PA, Mion D Jr, Martins MA: Blood pressure behaviour in chronic daily headache. Cephalalgia 2002, 22: 190–194. 10.1046/j.1468-2982.2002.00340.xPubMedCrossRef

31.

Busija DW, Leffler CW: Dilator effects of amino acid neurotransmitters on piglet pial arterioles. Am J Physiol 1989, 257: H1200-H1203.PubMed

32.

Cairns BE, Gambarota G, Dunning PS, Mulkern RV, Berde CB: Activation of peripheral excitatory amino acid receptors decreases the duration of local anesthesia. Anesthesiology 2003, 98: 521–529. 10.1097/00000542-200302000-00035PubMedCrossRef

33.

Fergus A, Lee KS: Regulation of cerebral microvessels by glutamatergic mechanisms. Brain Res 1997, 754: 35–45. 10.1016/S0006-8993(97)00040-1PubMedCrossRef

34.

Bagdy G, Riba P, Kecskeméti V, Chase D, Juhász G: Headache-type adverse effects of NO donors: vasodilation and beyond. Br J Pharmacol 2010, 160: 20–35. 10.1111/j.1476-5381.2010.00643.xPubMedCentralPubMedCrossRef

35.

Ashina M, Tfelt-Hansen P, Dalgaard P, Olesen J: Lack of correlation between vasodilatation and pharmacologically induced immediate headache in healthy subjects. Cephalalgia 2011, 31: 683–690. 10.1177/0333102410394672PubMedCrossRef

36.

Hansen JM, Pedersen D, Larsen VA, Sánchez-del-Rio M, Alvarez Linera JR, Olesen J, Ashina M: Magnetic resonance angiography shows dilatation of the middle cerebral artery after infusion of glyceryl trinitrate in healthy volunteers. Cephalalgia 2007, 27: 118–127. 10.1111/j.1468-2982.2006.01257.xPubMedCrossRef

37.

Asghar MS, Hansen AE, Amin FM, van der Geest RJ, Pv K, Larsson HB, Olesen J, Ashina M: Evidence for a vascular factor in migraine. Ann Neurol 2011, 69: 635–645. 10.1002/ana.22292PubMedCrossRef

38.

Burstein R, Jakubowski M, Rauch SD: The science of migraine. J Vestib Res 2011, 21: 305–314. 10.3233/VES-2012-0433PubMedCentralPubMed

39.

Chan KY, Gupta S, de Vries R, Danser AH, Villalón CM, Muñoz-Islas E, Maassenvandenbrink A: Effects of ionotropic glutamate receptor antagonists on rat dural artery diameter in an intravital microscopy model. Br J Pharmacol 2010, 160: 1316–1325. 10.1111/j.1476-5381.2010.00733.xPubMedCentralPubMedCrossRef

40.

Rutten EP, Engelen MP, Gosker H, Bast A, Cosemans K, Vissers YL, Wouters EF, Deutz NE, Schols AM: Metabolic and functional effects of glutamate intake in patients with chronic obstructive pulmonary disease (COPD). Clin Nutr 2008, 27: 408–415. 10.1016/j.clnu.2008.03.001PubMedCrossRef

41.

Yang WH, Drouin MA, Herbert M, Mao Y, Karsh J: The monosodium glutamate symptom complex: assessment in a double-blind, placebo-controlled, randomized study. J Allergy Clin Immunol 1997, 99: 757–762. 10.1016/S0091-6749(97)80008-5PubMedCrossRef

42.

Anderson GC, John MT, Ohrbach R, Nixdorf DR, Schiffman EL, Truelove ES, List T: Influence of headache frequency on clinical signs and symptoms of TMD in subjects with temple headache and TMD pain. Pain 2011, 152: 765–771. 10.1016/j.pain.2010.11.007PubMedCentralPubMedCrossRef

Title: Headache and mechanical sensitization of human pericranial muscles after repeated intake of monosodium glutamate (MSG)
Authors: Akiko Shimada
Brian E Cairns
Nynne Vad
Kathrine Ulriksen
Anne Marie Lynge Pedersen
Peter Svensson
Lene Baad-Hansen
Publication date: 01-12-2013
Publisher: Springer Milan
Published in: The Journal of Headache and Pain / Issue 1/2013
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI: https://doi.org/10.1186/1129-2377-14-2

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Headache and mechanical sensitization of human pericranial muscles after repeated intake of monosodium glutamate (MSG)

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2013

Cephalalgiaphobia as a feature of high-frequency migraine: a pilot study

Health-care utilization for primary headache disorders in China: a population-based door-to-door survey

Carotid dissection mimicking a new attack of cluster headache

Management of secondary chronic headache in the general population: the Akershus study of chronic headache

Self-reported headache among the employees of a Swiss university hospital: prevalence, disability, current treatment, and economic impact

Sleep-related and non-sleep-related migraine: interictal sleep quality, arousals and pain thresholds