Influence of Gender on pain: In Temporomandibular Disorders

Jeffry Rowland Shaefer, Paula Furlan Bavia, Shehryar N. Khawaja


Most patients with TMD disorders will respond to non-operative therapy involving; control of parafunctional behaviors, exercises to restore good jaw function, and use of analgesics and muscle relaxers during episodes of acute pain and dysfunction. But up to 20% of TMD patients will not respond to these conventional treatments and multiple factors influenced by gender can be responsible for this poor response.Prolonged nociception in such patients can lead to the peripheral and central nervous system sensitization, as evidenced by low pain thresholds and temporal summation, routinely encountered in patients with chronic TMD symptoms, but also female patients in general. Tailoring treatment to address these gender –based contributing factors is the challenge that providers must meet for successful management of chronic TMD patients. This chapter evaluates gender as an initiating, predisposing, or  perpetuating factor for TMD via the role of sex hormones, muscle activity and parafunctional behaviors, pain perception, and genetics.




gender, TMD, parasomnias, pain

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Greene CS. Diagnosis and treatment of temporomandibular disorders: emergence of a new care guidelines statement. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. Aug 2010;110(2):137-139.

Shinal RM, Fillingim RB. Overview of orofacial pain: epidemiology and gender differences in orofacial pain. Dental clinics of North America. Jan 2007;51(1):1-18, v.

Schiffman EL, Ohrbach R, Truelove E, et al. Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for Clinical and Research Applications: Recommendations of the International RDC/TMD Consortium Network and Orofacial Pain Special Interest Group. Journal of orofacial pain. 2013;In Press.

LeResche L. Epidemiology of temporomandibular disorders: implications for the investigation of etiologic factors. Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists. 1997;8(3):291-305.

Slade GD, Bair E, By K, et al. Study methods, recruitment, sociodemographic findings, and demographic representativeness in the OPPERA study. The journal of pain : official journal of the American Pain Society. Nov 2011;12(11 Suppl):T12-26.

Sanders AE, Slade GD, Bair E, et al. General health status and incidence of first-onset temporomandibular disorder: the OPPERA prospective cohort study. The journal of pain : official journal of the American Pain Society. Dec 2013;14(12 Suppl):T51-62.

Dworkin SF, Huggins KH, LeResche L, et al. Epidemiology of signs and symptoms in temporomandibular disorders: clinical signs in cases and controls. Journal of the American Dental Association. Mar 1990;120(3):273-281.

Slade GD, Bair E, Greenspan JD, et al. Signs and symptoms of first-onset TMD and sociodemographic predictors of its development: the OPPERA prospective cohort study. The journal of pain : official journal of the American Pain Society. Dec 2013;14(12 Suppl):T20-32 e21-23.

National Institute of Dental and Craniofacial Research. Facial Pain. . Accessed 03/03/2014.

Shaefer JR, Holland N, Whelan JS, Velly AM. Pain and temporomandibular disorders: a pharmaco-gender dilemma. Dental clinics of North America. Apr 2013;57(2):233-262.

LeResche L, Mancl LA, Drangsholt MT, Saunders K, Von Korff M. Relationship of pain and symptoms to pubertal development in adolescents. Pain. Nov 2005;118(1-2):201-209.

Bulls HW, Freeman EL, Anderson AJ, Robbins MT, Ness TJ, Goodin BR. Sex differences in experimental measures of pain sensitivity and endogenous pain inhibition. J Pain Res. 2015;8:311-320.

Ida Silva LA, Lin SM, Teixeira MJ, de Siqueira JT, Jacob Filho W, de Siqueira S. Sensorial differences according to sex and ages. Oral Dis. Apr 2014;20:103-110.

Petrini L, Matthiesen ST, Arendt-Nielsen L. The effect of age and gender on pressure pain thresholds and suprathreshold stimuli. Perception. 2015;44(5):587-596.

Racine M, Tousignant-Laflamme Y, Kloda LA, Dion D, Dupuis G, Choiniere M. A systematic literature review of 10 years of research on sex/gender and experimental pain perception - part 1: are there really differences between women and men? Pain. Mar 2012;153:602-618.

Nosotti M, Rosso L, Tosi D, et al. Preventive analgesia in thoracic surgery: controlled, randomized, double-blinded study. Eur J Cardiothorac Surg. Sep 2015;48(3):428-433; discussion 434.

Peng Z, Li H, Zhang C, Qian X, Feng Z, Zhu S. A retrospective study of chronic post-surgical pain following thoracic surgery: prevalence, risk factors, incidence of neuropathic component, and impact on qualify of life. PLoS One. 2014;9(2):e90014.

Oksholm T, Rustoen T, Cooper B, et al. Trajectories of Symptom Occurrence and Severity From Before Through Five Months After Lung Cancer Surgery. J Pain Symptom Manage. Jun 2015;49(6):995-1015.

Bjornnes AK, Rustoen T, Lie I, Watt-Watson J, Leegaard M. Pain characteristics and analgesic intake before and following cardiac surgery. Eur J Cardiovasc Nurs. Feb 2016;15(1):47-54.

Totonchi Z, Seifi S, Chitsazan M, Alizadeh Ghavidel A, Baazm F, Faritus SZ. Pain location and intensity during the first week following coronary artery bypass graft surgery. Anesth Pain Med. Feb 2014;4(1):e10386.

Morze CJ, Johnson NR, Williams G, Moroney M, Lamberton T, McAuliffe M. Knee pain during the first three months after unilateral total knee arthroplasty: a multi-centre prospective cohort study. J Arthroplasty. Oct 2013;28(9):1565-1570.

Sumitani M, Yasunaga H, Uchida K, et al. Perioperative factors affecting the occurrence of acute complex regional pain syndrome following limb bone fracture surgery: data from the Japanese Diagnosis Procedure Combination database. Rheumatology (Oxford). Jul 2014;53(7):1186-1193.

Valencia C, Fillingim RB, Bishop M, et al. Investigation of central pain processing in postoperative shoulder pain and disability. Clin J Pain. Sep 2014;30(9):775-786.

Bouman EA, Theunissen M, Bons SA, et al. Reduced incidence of chronic postsurgical pain after epidural analgesia for abdominal surgery. Pain Pract. Feb 2014;14(2):E76-84.

Theodoraki K, Staikou C, Fassoulaki A. Postoperative pain after major abdominal surgery: is it gender related? An observational prospective study. Pain Pract. Sep 2014;14(7):613-619.

Law AS, Nixdorf DR, Aguirre AM, et al. Predicting severe pain after root canal therapy in the National Dental PBRN. J Dent Res. Mar 2015;94(3 Suppl):37S-43S.

Mantovani E, Arduino PG, Schierano G, et al. A split-mouth randomized clinical trial to evaluate the performance of piezosurgery compared with traditional technique in lower wisdom tooth removal. J Oral Maxillofac Surg. Oct 2014;72(10):1890-1897.

Osunde OD, Saheeb BD. Effect of age, sex and level of surgical difficulty on inflammatory complications after third molar surgery. J Maxillofac Oral Surg. Mar 2015;14(1):7-12.

Sadaf D, Ahmad MZ. Factors associated with postoperative pain in endodontic therapy. Int J Biomed Sci. Dec 2014;10(4):243-247.

Marchiori EC, Barber JS, Williams WB, Bui PQ, O'Ryan FS. Neuropathic pain following sagittal split ramus osteotomy of the mandible: prevalence, risk factors, and clinical course. J Oral Maxillofac Surg. Dec 2013;71(12):2115-2122.

Fillingim RB, King CD, Ribeiro-Dasilva MC, Rahim-Williams B, Riley JL, 3rd. Sex, gender, and pain: a review of recent clinical and experimental findings. J Pain. May 2009;10(5):447-485.

Ip HY, Abrishami A, Peng PW, Wong J, Chung F. Predictors of postoperative pain and analgesic consumption: a qualitative systematic review. Anesthesiology. Sep 2009;111(3):657-677.

Forsythe LP, Thorn B, Day M, Shelby G. Race and sex differences in primary appraisals, catastrophizing, and experimental pain outcomes. J Pain. May 2011;12(5):563-572.

Huang GJ, LeResche L, Critchlow CW, Martin MD, Drangsholt MT. Risk factors for diagnostic subgroups of painful temporomandibular disorders (TMD). Journal of dental research. Apr 2002;81(4):284-288.

Blanco-Hungria A, Blanco-Aguilera A, Blanco-Aguilera E, et al. Prevalence of the different Axis I clinical subtypes in a sample of patients with orofacial pain and temporomandibular disorders in the Andalusian Healthcare Service. Medicina oral, patologia oral y cirugia bucal. Mar 2016;21(2):e169-177.

Johansson A, Unell L, Carlsson GE, Soderfeldt B, Halling A. Gender difference in symptoms related to temporomandibular disorders in a population of 50-year-old subjects. Journal of orofacial pain. Winter 2003;17(1):29-35.

Bagis B, Ayaz EA, Turgut S, Durkan R, Ozcan M. Gender difference in prevalence of signs and symptoms of temporomandibular joint disorders: a retrospective study on 243 consecutive patients. International journal of medical sciences. 2012;9(7):539-544.

Michelotti A, Cioffi I, Festa P, Scala G, Farella M. Oral parafunctions as risk factors for diagnostic TMD subgroups. Journal of oral rehabilitation. Mar 2010;37(3):157-162.

Kuttila M, Niemi PM, Kuttila S, Alanen P, Le Bell Y. TMD treatment need in relation to age, gender, stress, and diagnostic subgroup. Journal of orofacial pain. Winter 1998;12(1):67-74.

Fillingim RB, Slade GD, Diatchenko L, et al. Summary of findings from the OPPERA baseline case-control study: implications and future directions. The journal of pain : official journal of the American Pain Society. Nov 2011;12(11 Suppl):T102-107.

Fillingim RB, Ness TJ. Sex-related hormonal influences on pain and analgesic responses. Neuroscience and biobehavioral reviews. Jun 2000;24(4):485-501.

Levitt SR, McKinney MW. Validating the TMJ scale in a national sample of 10,000 patients: demographic and epidemiologic characteristics. Journal of orofacial pain. Winter 1994;8(1):25-35.

LeResche L, Sherman JJ, Huggins K, et al. Musculoskeletal orofacial pain and other signs and symptoms of temporomandibular disorders during pregnancy: a prospective study. Journal of orofacial pain. Summer 2005;19(3):193-201.

Isselee H, De Laat A, De Mot B, Lysens R. Pressure-pain threshold variation in temporomandibular disorder myalgia over the course of the menstrual cycle. Journal of orofacial pain. Spring 2002;16(2):105-117.

Abubaker AO, Raslan WF, Sotereanos GC. Estrogen and progesterone receptors in temporomandibular joint discs of symptomatic and asymptomatic persons: a preliminary study. Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. Oct 1993;51(10):1096-1100.

Abubaker AO, Hebda PC, Gunsolley JN. Effects of sex hormones on protein and collagen content of the temporomandibular joint disc of the rat. Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. Jun 1996;54(6):721-727; discussion 727-728.

Puri V, Cui L, Liverman CS, et al. Ovarian steroids regulate neuropeptides in the trigeminal ganglion. Neuropeptides. Aug 2005;39(4):409-417.

Flake NM, Bonebreak DB, Gold MS. Estrogen and inflammation increase the excitability of rat temporomandibular joint afferent neurons. Journal of neurophysiology. Mar 2005;93(3):1585-1597.

Flake NM, Hermanstyne TO, Gold MS. Testosterone and estrogen have opposing actions on inflammation-induced plasma extravasation in the rat temporomandibular joint. American journal of physiology. Regulatory, integrative and comparative physiology. Aug 2006;291(2):R343-348.

Dao TT, Knight K, Ton-That V. Modulation of myofascial pain by the reproductive hormones: a preliminary report. The Journal of Prosthetic Dentistry. Jun 1998;79(6):663-670.

LeResche L, Saunders K, Von Korff MR, Barlow W, Dworkin SF. Use of exogenous hormones and risk of temporomandibular disorder pain. Pain. Jan 1997;69(1-2):153-160.

Benoliel R, Sela G, Teich S, Sharav Y. Painful temporomandibular disorders and headaches in 359 dental and medical students. Quintessence international. Jan 2011;42(1):73-78.

Hatch JP, Rugh JD, Sakai S, Saunders MJ. Is use of exogenous estrogen associated with temporomandibular signs and symptoms? Journal of the American Dental Association. Mar 2001;132(3):319-326.

Reynolds AK, Nickel JC, Liu Y, et al. Sex differences in jaw muscle duty factors during exercise in two environments: A pilot study. Journal of electromyography and kinesiology : official journal of the International Society of Electrophysiological Kinesiology. May 18 2016;30:15-22.

Khawaja SN, McCall W, Jr., Dunford R, et al. Infield masticatory muscle activity in subjects with pain-related temporomandibular disorders diagnoses. Orthodontics & craniofacial research. Apr 2015;18 Suppl 1:137-145.

Frontera WR, Hughes VA, Lutz KJ, Evans WJ. A cross-sectional study of muscle strength and mass in 45- to 78-yr-old men and women. Journal of applied physiology. Aug 1991;71(2):644-650.

Farella M, Palla S, Erni S, Michelotti A, Gallo LM. Masticatory muscle activity during deliberately performed oral tasks. Physiological measurement. Dec 2008;29(12):1397-1410.

Ohrbach R, Bair E, Fillingim RB, et al. Clinical orofacial characteristics associated with risk of first-onset TMD: the OPPERA prospective cohort study. The journal of pain : official journal of the American Pain Society. Dec 2013;14(12 Suppl):T33-50.

Ohrbach R, Fillingim RB, Mulkey F, et al. Clinical findings and pain symptoms as potential risk factors for chronic TMD: descriptive data and empirically identified domains from the OPPERA case-control study. The journal of pain : official journal of the American Pain Society. Nov 2011;12(11 Suppl):T27-45.

Winocur E, Littner D, Adams I, Gavish A. Oral habits and their association with signs and symptoms of temporomandibular disorders in adolescents: a gender comparison. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. Oct 2006;102(4):482-487.

Cairns BE, Hu JW, Arendt-Nielsen L, Sessle BJ, Svensson P. Sex-related differences in human pain and rat afferent discharge evoked by injection of glutamate into the masseter muscle. Journal of neurophysiology. Aug 2001;86(2):782-791.

Cairns BE, Sessle BJ, Hu JW. Characteristics of glutamate-evoked temporomandibular joint afferent activity in the rat. Journal of neurophysiology. Jun 2001;85(6):2446-2454.

Cairns BE, Gambarota G, Svensson P, Arendt-Nielsen L, Berde CB. Glutamate-induced sensitization of rat masseter muscle fibers. Neuroscience. 2002;109(2):389-399.

Khawaja SN, Nickel JC, Iwasaki LR, Crow HC, Gonzalez Y. Association between waking-state oral parafunctional behaviours and bio-psychosocial characteristics. Journal of oral rehabilitation. Apr 16 2015.

Battie MC, Videman T, Levalahti E, Gill K, Kaprio J. Heritability of low back pain and the role of disc degeneration. Pain. Oct 2007;131(3):272-280.

MacGregor AJ, Andrew T, Sambrook PN, Spector TD. Structural, psychological, and genetic influences on low back and neck pain: a study of adult female twins. Arthritis Rheum. Apr 15 2004;51(2):160-167.

Raphael KG, Marbach JJ, Gallagher RM, Dohrenwend BP. Myofascial TMD does not run in families. Pain. Mar 1999;80(1-2):15-22.

Matsuka Y, Nagamatsu C, Itoh S, et al. Comparison of inter-twin concordance in symptoms of temporomandibular disorders: a preliminary investigation in an adolescent twin population. Cranio. Jan 2007;25(1):23-29.

Michalowicz BS, Pihlstrom BL, Hodges JS, Bouchard TJ, Jr. No heritability of temporomandibular joint signs and symptoms. J Dent Res. Aug 2000;79(8):1573-1578.

Plesh O, Noonan C, Buchwald DS, Goldberg J, Afari N. Temporomandibular disorder-type pain and migraine headache in women: a preliminary twin study. J Orofac Pain. Spring 2012;26(2):91-98.

Visscher CM, Lobbezoo F. TMD pain is partly heritable. A systematic review of family studies and genetic association studies. J Oral Rehabil. May 2015;42(5):386-399.

Mutlu N, Erdal ME, Herken H, Oz G, Bayazit YA. T102C polymorphism of the 5-HT2A receptor gene may be associated with temporomandibular dysfunction. Oral Dis. Nov 2004;10(6):349-352.

de Freitas LV, Lopes AC, Piatto VB, Maniglia JV. Association of temporomandibular dysfunction with the 102T-C polymorphism in the serotonin receptor gene in Brazilian patients. Arch Med Sci. Dec 30 2013;9(6):1013-1018.

Herken H, Erdal E, Mutlu N, et al. Possible association of temporomandibular joint pain and dysfunction with a polymorphism in the serotonin transporter gene. Am J Orthod Dentofacial Orthop. Sep 2001;120(3):308-313.

Ojima K, Watanabe N, Narita N, Narita M. Temporomandibular disorder is associated with a serotonin transporter gene polymorphism in the Japanese population. Biopsychosoc Med. 2007;1:3.

Bardin L, Tarayre JP, Malfetes N, Koek W, Colpaert FC. Profound, non-opioid analgesia produced by the high-efficacy 5-HT(1A) agonist F 13640 in the formalin model of tonic nociceptive pain. Pharmacology. Apr 2003;67(4):182-194.

Andersen S, Skorpen F. Variation in the COMT gene: implications for pain perception and pain treatment. Pharmacogenomics. Apr 2009;10(4):669-684.

Zubieta JK, Heitzeg MM, Smith YR, et al. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science. Feb 21 2003;299(5610):1240-1243.

Nackley AG, Tan KS, Fecho K, Flood P, Diatchenko L, Maixner W. Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both beta2- and beta3-adrenergic receptors. Pain. Apr 2007;128(3):199-208.

Diatchenko L, Slade GD, Nackley AG, et al. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet. Jan 1 2005;14(1):135-143.

Diatchenko L, Anderson AD, Slade GD, et al. Three major haplotypes of the beta2 adrenergic receptor define psychological profile, blood pressure, and the risk for development of a common musculoskeletal pain disorder. Am J Med Genet B Neuropsychiatr Genet. Jul 5 2006;141B(5):449-462.

Smith SB, Maixner DW, Greenspan JD, et al. Potential genetic risk factors for chronic TMD: genetic associations from the OPPERA case control study. J Pain. Nov 2011;12(11 Suppl):T92-101.

Meloto CB, Segall SK, Smith S, et al. COMT gene locus: new functional variants. Pain. Oct 2015;156(10):2072-2083.

Meloto CB, Bortsov AV, Bair E, et al. Modification of COMT-dependent pain sensitivity by psychological stress and sex. Pain. Apr 2016;157(4):858-867.

Scrivani SJ, Keith DA, Kaban LB. Temporomandibular disorders. N Engl J Med. Dec 18 2008;359(25):2693-2705.

Dym H, Bowler D, Zeidan J. Pharmacologic Treatment for Temporomandibular Disorders. Dent Clin North Am. Apr 2016;60(2):367-379.

Freire AC, Basit AW, Choudhary R, Piong CW, Merchant HA. Does sex matter? The influence of gender on gastrointestinal physiology and drug delivery. Int J Pharm. Aug 30 2011;415(1-2):15-28.

Anderson GD. Sex and racial differences in pharmacological response: where is the evidence? Pharmacogenetics, pharmacokinetics, and pharmacodynamics. J Womens Health (Larchmt). Jan-Feb 2005;14(1):19-29.

Gandhi M, Aweeka F, Greenblatt RM, Blaschke TF. Sex differences in pharmacokinetics and pharmacodynamics. Annu Rev Pharmacol Toxicol. 2004;44:499-523.

Tanaka E. Gender-related differences in pharmacokinetics and their clinical significance. J Clin Pharm Ther. Oct 1999;24(5):339-346.

Franconi F, Brunelleschi S, Steardo L, Cuomo V. Gender differences in drug responses. Pharmacol Res. Feb 2007;55(2):81-95.

Nicolson TJ, Mellor HR, Roberts RR. Gender differences in drug toxicity. Trends Pharmacol Sci. Mar 2010;31(3):108-114.

Anderson GD. Gender differences in pharmacological response. Int Rev Neurobiol. 2008;83:1-10.

Spaanderman ME, Van Beek E, Ekhart TH, et al. Changes in hemodynamic parameters and volume homeostasis with the menstrual cycle among women with a history of preeclampsia. Am J Obstet Gynecol. May 2000;182(5):1127-1134.

Waxman DJ, Holloway MG. Sex differences in the expression of hepatic drug metabolizing enzymes. Mol Pharmacol. Aug 2009;76(2):215-228.

Meibohm B, Beierle I, Derendorf H. How important are gender differences in pharmacokinetics? Clin Pharmacokinet. 2002;41(5):329-342.

Schwartz JB. The influence of sex on pharmacokinetics. Clin Pharmacokinet. 2003;42(2):107-121.



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