muscle-related temporomandibular disorders

Muscle-Related Temporomandibular Disorders

Christian S. Stohler. DDS,Dr med dent

William R. Mann Professor and CbairDepartment of Biologic and Materials

SciencesSchool of DentistryThe University of MichiganAnn Arbor, Michigan

Correspondence to:Dr Christian S. StoblerDepartment of Biologic and Matetials

SciencesSchool of DentistryThe University of Michigan1011 N. UniversityAnn Arbor. Ml 48109-1078E-mail: [email protected]

R apid developments in laboratory-based research in tbe pastdecade have provided important new insight into tbe cellu-lar and molecular mechanisms of nociception. However,

the integration of tbe new understanding into clinical practice ishampered by our inability to combine discrete and often disparatebodies of knowledge and to translate new facts into a perspectiveof disease-specific significance and case-specific relevance. Thisprocess is also inhibited by the current classification systems,which focus heavily on the peripheral anatomy and provide littleroom to incorporate new understanding of the central nervous sys-tem (CNS) in the pathogenesis of disease. If central targets becomethe ob|ect of treatment, crtide and often invalid measures of CNS,neuroendocrine, and autonomie processes are used as justification.With the widening gap between bench top-derived researcb dataand clinical practice, an effort needs to be made to translate thebasic science frontier into meaning for patienrs.

The muscle-related conditions constitute the most enigmaticsubset among the rempotomandibular disorders (TMD), Theseconditions aiso represent the most prevalent presentations amongthe TMD, with at least 50% of cases falling into this category.Intense research in rhe past 10 years has resulted in (1) animproved epidemiologic and clinical description of the phe-nomenon; (2) new understanding of the molecular, neurophysio-logic, and psychophysiologic mechanisms of nociception; and (3)the emergence of metabolic, neuroendocrinologic, and geneticfindings,

Ratber tban focusing on the dismissal of previous etiologic con-structs, this paper attempts to define what tbe muscle-relatedTMD are rather than what they are not. Special consideration isgiven to the large spectrum of case presentations and the fact thatrhe more severe and persistent forms occur in women more oftenthan in men. With this perspective in mind, the intent of this pro-ject was to develop a conceptual framework of the pathogenesisand clinical phenomenology of the muscle-related TMD,

Conceptual Framework

Although the initiating sequence of events that leads ro the devel-opment of muscle-related TMD remains unknown, key attributes.

Key words: allodynia, sensitization, neuroplasticity,neuroendocrine system, autonomie system,gender differences

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To thalamusDirect pain paliiway

Sensory Muscle groups Motor

Fig 1 Explanatory model of tbe patbogenesis of muscie-related T.VII) symptoms and signs.See text for details.

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such as tenderness to palpation of muscle, limita-tion in mandibuiar range of motion, perceivedalterarion in the dental occlusion, and changes inmood, are conceptuaUzed as consequences of pain.Mechanisms that underlie the generation of symp-toms and signs include the sensitization of periph-eral tissue, central neuroplasticity and sensitizationin pro-nociceptive atid anti-nociceptive systems,neuroendocrine and autonomie stress effecrs, andrhe consequences of pain on motor funcrion, emo-tional state, and cognition. The wide range of clin-ical presentations is explained by variations in theoverall response or irs components among individ-ual patients. Attributes encountered in the moreserious cases include sleep disturbances, weightloss or weight gain, loss of libido or drive, andmemory effects. Answers to explain the vulnerabil-ity of women to, on average, greater severity andpersistence of pain must be found in the modula-tory effect of female hormones in peripberal andcentral targets, such as neuroendocrine, auto-nomie, and emotional centers (Fig 1).

Clinical Phenomenology

Case Definition

The muscle-related TMD should not be under-stood as a single, discrete disease enrirv-. Instead, anumber of related and often overlapping condi-tions are included under this umbrella term, withpain being the main symptom. Most muscle-related pam conditions are identified on the basisof clinical attributes; there are no biomarkers ofexposure or effect rhar would permit both validand reliable case ascertainment. Prevalence figuresdepend to a large exrenr on the case definitionemployed. As a consequence, prevalence data varyconsiderably from invesrigation to investigation.This inconsistency frequently creates confusion,particularly in discussions of rrearment need.

To standardize diagnosis, the National Instituteof Dental and Craniofacial Research (NIDCR),assisted by the Pain Research Group at theUniversity of Washington, has sponsored thedevelopment of a diagnostic system for the TMD(RDCn"MD). This dual-axial system requires onAxis I a report of pain or ache in the jaw, temples,face, preauricular area, or inside the ear at rest orduring function, in combination wirh tenderness topalpation of 3 or more of 20 palpation sites, withat least 1 of the sites being on the same side as thecomplaint of pain. Applicable palpation sitesinclude the posterior temporalis, middle tempo-

ralis, anterior temporalis, origin of masserer, bodyof masseter, insertion point of masseter, posteriormandibular region, submandibular region, lateralpterygoid area, and tendon of the temporalis, withthe right side and left side counting as separatesites. Axis II criteria serve ro assess pain intensity,pain-related disability, and the presence of depres-sion and non-specific physical symptoms.'

Observational Setting

Information on rhe muscle-related TMD is con-texr-bound. To appreciare rhe breadth of the clini-cal spectrum, community cases and patients in pri-mary or even tertiary care settings need to bedistinguished. These broad categories of care set-tings would be irrelevant if tbere were no meaning-ful variation in case characteristics among subjectsencountered under these different conditions.However, the occurrence of pam; irs severity,spread, and impacr; and the presence of comorbidcondirions vary considerably among cases identi-fied in these settings. While infrequent masticatorymuscle pain, comparable to an occasional head-ache, represents a nuisance rather than a reason toseek care, longer-la s ting pains are less likely to beneglected. Previous treatment failure and the con-tinued persisrence of pain and dysfunction charac-terize terriary care cases. It is also important torecognize tbat the proportion of women amongcases increases from community-based observa-tions to primary and tertiary care settings, withwomen comprising 90% or more of patient popu-lations in academic researcb centers.

Time-Varying Characteristics

Data on tbe time-varying nature of muscle-relatedTMD are limired. Only a small percentage of casescontinue to be labeled as muscle conditions accord-ing to the RDC/TxMD at rhe 1-year (23%), 3-year(13.3%), and 5-year (6.7%) follow-up examina-tions. Aside from tbe fact that more than half thecases resolve with time, only rarely do muscle-related TMD seem to persist over a period of 5years without clinical indicators being suggestive ofrhe involvement of the temporomandibular joint.^

Pain Involvement

Muscle pain conditions are often not limited to asingle topographic domain. Subjects who seekadvice in a dental setting may experience pain inparts of the body other than the trigeminal system;however, they are not likely to report pain outside


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Fig 2 Pain drawing of a patient with muscle-relatedTMD,

the head and face to a dentist. In their chief com-plaint, only 29% of adult TMD patients acknowl-edged the presence of pain outside the head/faceregion.^ Among cases encountered in academicresearch centers, widespread pain involvement isanything but rare. In a series of 200 consecutivefemale patients, only 18,5% of subjects exhibitedpain that was limited to the trigeminal system.Between 55 and 60% of cases showed involvementof any or all of the cervical dermatomes C2 to C6.As far as thoracic dermatomes are concerned,spontaneous pain was noted in as many as 15 to34% of cases. In the overwhelming majority ofcases, pain was bilateral,''

Overlapping Pain Conditions

Because patients with 2 diseases have a greater like-lihood of being referred than subjects with only 1disease, the resulting bias produced by such differ-ential referral ro research centers could result in anoverestiniation of the problem of disease overlap.

Pain conditions that are often observed in com-bination with muscle-related TMD include head-ache, regional myofascial pain involving the neckand shoulders, and fibromyalgia syndrome (FMS).Myofascial pain is understood as a local-regionalpain disorder, with the muscJe-reiated TMD beinga form of myofascial pain that is focused on themuscles of mastication (Fig 2), Regional paininvolvement extends to the muscles of the neckand shoulder.'' The classic text on myofa.scial painassociates the condition with so-called triggerpoints, which when "active" have been describedto refer pain to specific body locations.^

Unfortunately, most observations on the subject oftrigger points are uncontrolled and subject to clim-cian bias. Consequently, tbe phenomenon ormyofascial pain, despite its high prevalence andclinical significance, remains insufficiently under-stood.

In contrast to this local-regional muscle pain dis-order, FMS is a clinical disorder that is character-ized by persistent widespread pain and tendernessto 4 kg of pressure at 11 of 18 predefinedanatomic sites. Pain is considered widespreadwhen all of the following criteria are met: (1) leftside body pain, (2) right side body pain, (3) painabove the waist, and (4) pain below the waist.Widespread pain must have been present for atleast 3 months.^ Emotional distress; fatigue; sleepdisturbance (restlessness, insomnia, and earlyawakening); beadache; and irritable bowel syn-drome often occur in combination with thewidespread pain and tenderness. About 2% of thegeneral population, 3.5% of females (often aroundthe onset of menopause), and 0,5% of males fulfillthe criteria of FMS of the American College ofRheumatology.'

As in the case of TMD, community FMSpatients distinguish themselves from those whoseek care. Treatment-seeking FMS patients aremore likely to exhibit elevated rates of psychiatricillness when compared with non-treatment-seek-ing subjects," In fact, the disabling nature of FMSis responsible for 9% of all long-term disabilityclaims of a major Canadian life insurance com-pany, with annual payments of about $200 million(Canadian) about 10 years ago,' As far as tbe rela-tionship of FMS to muscle-related TMD is con-cerned, recent studies performed in academicresearch centers have shown significant overlap ofthe 2 conditions,'""'^ According to Plesh andcoworkers,"' 75% of FMS patients had TMD,while on the other hand, 18% of cases with TMDmet the diagnostic criteria for FMS.

The diagnostic system of the InternationalHeadache Society classifies headaches based on theclinical features of individual episodes,'^ To beclassified as a tension-type headache, a minimumof 10 headaches of mild to moderate intensity andbilateral pain distribution, la.sting from 30 minutesto 7 days, is required. The key diagnostic featureof migraine consists of the experience of at least 5unilateral headache attacks that last between 4 and72 hours. Population-based and clinic-based stud-ies indicate that women are more often affecredthan men for these types of headache in terms offrequency, duration, and severity (for review, seeUnruhi").

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Many epidemiologic studies report a high asso-ciation betweeti the TMD and the 2 most commontypes of headache, tension-type and migraine."Because of this association, some authors go as faras considering headache part of the symptom cotn-plex of TMD.'* As far as overlapping signsbetween the TMD and these types of headache areconcerned, there is a greater chance for a subjectto exhibit perictanial muscle tenderness whenaffected by tension-type headache than bymigrame headache.' -' With tenderness to palpa-tion being another essential diagnostic feature ofthe muscle-related TMD, it becomes obvious thatthe boundary between these types of headache andthe muscle-related TMD is indistinct.

Susceptibility Risk

Variations in prevalence rates of muscle-relatedTMD among different populations often provideinsight into their etiopathogenesis. Unlike mostchronic pain conditions, for which the relativeimportance of chronic illnesses and their impact onfunctional limitation increases as subjects age, themuscle-related TMD represent an exception.Prevalence rates are lower among older subjects,and the initial onset in both males and females ismore likely to occur before age 50 than later inlife. However, this does not mean that severesymptoms cannot occur later in life."

More recent studies that focus on TNÍD typesrather than individual signs and symptoms indicatethat more women than men are affected by facialpain. Among women, prevalence rates are higherfor subjects of reproductive age than subjects inpostmenopausal years.'•*•-' Chances of seekingtreatment increase by 77% with the use of supple-mental estrogen in the postmenopausal years, orby 19% in subjects using oral contraceptives.-'Pain on palpation of masticatory muscles is signifi-cantly more prevalent among women than men.-In children and young adults, gender differencesare not clear.-''•^^ With respect to gender effectsobserved in persistent pain conditions mvolvingtissues adjacent to the face, women also havehigher prevalence rates for chronic tension head-ache and neck pain {fot review, see Unruh'*^).

Aside from age, sex, and the use of estrogen sup-plements there are no other factors consistentlyreported as increasing the susceptibility risk for themuscle-related TMD and any of the related painconditions. Cross-culturally, no differences appearto exist: the muscle-related TMD represent about50% of both United States and Swedish TMDcases.^* Thus far, race and socioeconomic status

do not appear to be an issue. According to the1989 National Health Interview Survey in theUnited States, prevalence rates for facial and jawpain were 7% for whites and 5% for blacks (notof Hispanic origin].-''

Increasing awareness of the genetic contributionto disease has stimulated discussion about thepotential role of genes. The underlying conceptstates that in a genetically predisposed individual,(1) susceptibility to the disease itself, (2) suscepti-bility to follow a particular clinical course, or (3)susceptibiht}' to a varying response to treatment isdetermined by polymorphism affecting DNAsequences of (mostly several) genes. It is estimatedthat about 30% of enzyme loci exhibit polymor-phism, with subtle differences forming the basis ofaltered enzymatic activity when compared to thestandard enzyme. However, the genetic contribu-tion to susceptibility to muscle-related TMD hasnot been subject to systematic research by geneticepidemiologists, and data on the related pain con-ditions are limited as well. Whether the observedfamilial aggregation in FMS patients is due togenetic influence or a common family environmentcannot be resolved with certainty at this time. ^

Although the role of genetic factors is in ques-tion, one recent finding is worth mentioningbecause it points to the possibility of genetic sus-ceptibility at the target site of a variety of drugsthat exhibit modest pain relief in conditions of per-sistent muscle pain. Polymorphism in the serotonintransporter gene regulatory promoter region hasbeen linked to anxiery-related traits.-' The sero-tonin transporter is responsible for the inactivationof the serotonin release in the synaptic cleft. Drug-induced enhancement of the serotonergic transmis-sion, on the other hand, has been associated withthe amelioration of depression, anxiety, and pain.Whether this finding has any relevance in the mus-cle-related TMD remains to be seen.

Causation and Pathogenesis

Causation Models

Biologic, familial, chemical, physical, occupa-tional, and psychosocial factors have been consid-ered as potential causes of muscle-related TMD;however, no necessary or sufficient cause has beenidentified. The possibility that muscle-relatedTMD are composed of subtypes that are etiologi-cally distinct cannot be excluded. There is also noreason to assume a common etiology for muscle-related TMD and other related pain conditions,

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even though these conditions may share commondownstream effecrs.

Proposed causation models range from simpleunifactoria! to complex biopsychosocial models ofStressors and predisposition. Popular unifacrotialmodels assume that serotonin deficiency is pivotalto these muscle pain conditions, or that musclehyperactlvity due to structural or psychologicabnormality iniriates a vicious circle of persistentpain and dysfunction. Many assumptions underly-ing popular causal models are missing either rhekey evidence in their support or oversimplify therole of the CNS to an extent that rhe construct nolonger gives justice to rhe biologic substrate. Morerealistic constructs tbar are based on rhe deficientmodulation of nociceprive and anti-nociceptiveinformation or the dysfunction of the bypothala-mic-pituitary-adrenal system (HPA) are based oncircumstantial evidence in support of tbe assump-tion of cause and effect. No single model of tbecausation of muscle-related TMD has emerged asbeing tbe most valid at this time.

Peripheral Sensitization

There is a lowered response threshold of nocicep-tors to mechanical and thermal stimuli in the stateof inflammation or tissue damage. This so-calledperipheral sensitization of nociceprive afférents *' isin contrast to the adaptive changes that occur inother somatosensory systems wirh continued stim-ulus presentation. The altered response character-istic is attributed to a range of chemical mediatorsthat are released from damaged tissue cells, mastcells, platelets, or rhe nociceptors themselves, andcan either activate (eg, histamine, hradykinin, sero-tonin, potassium) or sensirize (eg, substance P,prostaglandins, leukotrienes) free nerve end-ings. " ' ^ Nociceprors can also be activated bysympathetic stimulation following sensitization byan injury or inflammation.•*- Increasing the com-plexity of possible interactions, newer data suggestthat endogenous opioid peptides are synthesizedby inflammatory cells, which may be a mechanismby which anri-nociception is exerted in peripheral

In the context of peripheral sensitization,increasing interest focuses on nerve growth factor{NGF) as a mediator in persisrenr muscle pain,^-'Besides the role of NGF as a target-derived trophicfactor in early ontogeny, ir was shown that smalladult primary sensory neurons, particularly thosethat contain calcitonin gene-related peptide,express the high-affinity NGF receptor trkA.Systemic application of NGF causes hyperalgesia

in both neonatal and adult rats.^* Pretreatmentwith NGF antibody reduces or prevents car-rageenan-induced arthritis in rats. ' Becausehealthy volunteers developed pain in the bulbar,jaw, and truncal musculature following intra-venous injection of NGF, tbis secretory protemappears to be important in the patbogenesis ofmuscle-related TMD, Human volunteers injectedwitb NGF described the experience as "muscleoveruse pain," and women seemed to experiencepain for a longer time than men. ^ Indeed, estro-gen has been shown to up-regulate trkA messengerRNA and thereby ro affect the efficiency of NGFbinding.^' This could be one of a number of rea-sons for the increased persistence and severity ofmuscle pain conditions among women.

Nerve growth facror has also been shown tostimulate the production of substance P, somato-statin, and vasoactive intestinal polypeptide in sen-sory neurons and affects inflammatory cells thatexpress the trkA receptor, such as mast cells.Because mast cells are known to exist in the peri-mysium of muscle, and mast cell degranulation hasbeen shown to occur in muscle soreness followingstrenuous muscle work, there is a real possibilitythat NGF-related peripheral effects contribute roclinical muscle pain conditions.

Central Neuroplasticity and Sensitization

There is great benefit to be gained from conceptu-alizing the clinical muscle pain conditions in thecontext of neuroplasticity and central sensiti-zation, *' Regarding neuroplasticity, a distinction ismade between neural and bebavioral plasticity.Neuroplasticity refers to tbe reorganization of thenervous system based on mechanisms that influ-ence synaptic efficacy and connectivity at all levelsof the brain. Borh short-term ¡lasting minutes) andlong-rerm (lasting for hours and longer) changesare distinguished. Fxamples of behavioral plastic-ity include sensitizarion, habituation, and rehabili-tation, Sensirization describes rhe phenomenon ofan enhanced behavioral response; liabituation, onthe other hand, refers to the decrease in the behav-ioral response with repeated stimulus applications.At the level of cellular networks, a decrease in thesynaptic strength forms the basis of habituation,whereas sensitization involves rhe greater availahil-ity of excitatory neurotransmittcr in the synapriccleft. Neuroplasticity and sensitization provide thebasis for matching the response to the local condi-tion in terms of injury detection, pain avoidance,pain escape, and the need for rest of the injuredbody parr to promote recuperation.'"' Airhough


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neuroplasticity and sensitization have a sense ofpurpose iti the context of survival function, thevery same mechanisms seem to be involved in thegeneration of symptoms and signs that dominatethe clinical picture of muscle-related TMD,

With their first synapse, nociceptive afférentsarising from che jaw and neck musculature connecrto projection neurons and inhibitory or excitatoryinterneurons. The significant convergence of affer-ent input at this level explains the spread andreferral of pain.^"-'" In addition to nociceptiveinput, non-nociceptive afférents and descendinganti-nociceptive systems may influence theexcitability- of these neurons as well. Differenr neu-rotransmitters (eg, glutamate, aspartate, and sub-stance P) are implicated in evoking both fast andslow synaptic potentials by acting on NMDA,AMPA, and neurokinin-1 receptors.^" Among theexcitatory neurotransminers, suhsrance P, an 11-amino-acid neuropeptide, has been reeeiving mostattention because of its perceived relevance in con-ditions of persistent muscle pain. Studies inhumans have shown rhat substance P levels in thecerebrospinal fluid are elevated in FMS patientswhen compared with controls.''- Allodynia (seebelow), which is a key feature of muscle-relaredTMD, is associated with increased excitability ofrat dorsal horn neurons during spinal cord super-fusion with substance P,"* The increased excitabil-ity that is paralleled by enlargement of meehanore-ceprive fields of the second-order neurons is anexpression of the inflammation-induced neuropias-

Pro-Nociceptive Pathways

Nociceptive information arising from the musclesof the head and neck is relayed via che spinai cordand corresponding structures of the trigeminalbrain stem complex to subcortical and corticalcenters. '* A direct parhway, which connecrs withnuclei in the lateral part of the thaiamus, is pri-marily made up of ascending inpur from spinal ortrigeminai laminae I and V. Deeper layers (laminaeVI, VII, and VIII) contribute to an indirect painpathway, which targets the rericular formationbefore establishing a connection with nuclei in themedial porrion of the thalamus. The iatter systemis implicated in influencing hormone release fromthe hypothalamus and pituitary gland and isknown to affecr supraspinal autonomie reflexes. ItIS increasingly clear that the neurosecrerory func-tion of a particular cell type is not regulated by asingle neurotransmitter. Instead, the response ofhypothalamic neurosecretory cells is dependent on

a comhination of neurotransmitters, with hor-mones acring as modularors. Evidence further sug-gests that the lateral or direct parhway carries pre-dominanrly rhe sensory-discriminative informationof pain, while the indirect or medial pain pathwayis associated with more affective-motivationalaspects of pain. At the cortical level, the primarysomatosensory cortex is the target of che sensory-discriminacive information content of pain, andthere is evidence rhat the frontal lobe is linked topain and unpleasantness. All this is relevanrbecause certain therapies have been shown to exertdifferential effects in these 2 systems.*'

Ant i-Nociceptive Pathways

Descending inhibitory influences are exerted fromrhe cortex, diencephalon, areas such as the peri-aqueductal gray and periventricular gray in themidhrain, and the medulla on nociceptive neuronsin che subnueleus caudahs or spinal dorsal horn,'**Kociceptive neurons with input predominantlyfrom deep tissues appear to he especially influ-enced by such descending control, with the evi-dence further suggesting that the anti-nociceptiveinfluences are greater in tonic pain than in acutepain.''^'*' Endogenous opioid peptides and sero-tonin are impHcated in mediating these inhibitory,anti-nociceptive effects. High ievels of substance Pin che spinal cord are associated with low brainserotonin levels in rats,*"-^' In humans, low con-centrations of endogenous opioids in the cerebro-spinal fluid have been reporced in persistentpainful neuropathy,^' Antidepressanrs that demon-strate an analgésie effect when compared withplacebo are believed to exert this influence byfacilitating pam-inhibiting pathways.

Neuroendocrine and Autonomie Stress Response

Because abnormality in neuroendocrine functionexists in depressed persons, it has been suggestedthar stress-induced dysfunction of the HPA systemIS a factor in FMS and possibly orher related painconditions in which depressive symptoms areprevalent. As far as stress is concerned, 2 majorresponse patterns are distinguished. The acutetesponse supports the defense reaction; the chronicresponse pattern elicits a vigilance reaction.Complex neuroendocrine and autonomie mecha-nisms are in effect to influence any stress-induceddeviación from homeoscasis, with the hypothala-mus forming the major link between the CNS, theHPA axis, and the supraspinal autonomie reflexcenters.

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Environmental stimuli and emotional and cogni-tive factors influence the hypothalamic neurosecre-tory cells that regulate the release of neurohor-mones (eg, corticotropin-releasing hormone),which in turn affect the synthesis of hormones bythe pituitary gland. Synthesis of peripheral hor-mones, such as Cortisol from the adrenal cortex, isunder pituitary control by way of adrenocorti-cotropin. To increase complexity, hypothalamicand pituitary neurohormones have not only periph-eral but also central targets, which include alteringthe expression of neurotransmitter receptors andthereby affecting the neural regulation of auto-nomie reflexes, behavior, and emotional states. Forexample, corricotropin-releasing hormone is impli-cated in increasing arousal and emotionality, andadrenocorricotropin facilitates attention. On theotber hand, inputs from the cerebrospinal fluid andcirculatory system (hormones, neuropeptides, etc)function as feedback signals that affect the releaseof neurotransmitters and adjust the hypothalamicrelease of neurohormones.

In view of stress being a poorly defined con-struct and the highly interactive nature of the neu-roendocrine system, cause-effect questions are dif-ficult to resolve in clinical cases of muscle pain.Insight into the role of the HPA axis is furthercomplicared by the fact that cortisol is secreted ina circadian rhythm, with the lowest levels occur-ring at midnight and the highest levels at about 8in the morning, calling for hourly sampling totrack levels in serum. Because newer findings alsosuggest that the nature of the HPA systemresponse is specific for a particular type of Stressor,greater care is applicable in rhe synthesis of the lit-erature. If the current stress construct, which isbased on the assumption of non-specificity in theresponse to a wide range of Stressors, is no longervalid, many generalizations about catecholaminer-gic activation are no longer appropriate. Althoughneuroendocrine functions appear to be highly rele-vant in muscle-related TMD, detailed studies ofthe nature of tbeir contribution to the pathogenesisof symptoms and signs in the TMD are not yetavailable.

Diagnostic Criteria and Classification

Classification

Layzer'^ proposes a diagnostic system that isapplicable to the broad range of medical musclepain presentations and that divides the painfulmuscle conditions into focal and generalized man-

ifestations. Focal presentations of muscle pain arefurther divided into 2 categories, based onwhether muscle enlargement or induration is pres-ent. Focal muscle pain with swelling includes con-ditions such as neoplasm, trauma (hematoma),thrombophlebitis, infection (eg, streptococcalmyositis, painful leg in children witb influenza),inflammation (eg, eosinophilic fascitis), ischemia,toxic and metabolic disorders, and motor unithyperactivity states (eg, stiff-man syndrome,tetanus). These relatively rare conditions need tobe distinguished from myofascial pain in general,or specifically the muscle-related TMD tbat donot exbibit clear evidence of swelling. TheRDC/TMD, which deal witb the most commonpainful masticatory muscle conditions, require theuser to rule out muscle spasm, myositis, and con-tracture from conditions covered under theumbrella term of TMD.

Current classification systems categorize clinicalTMD entities and subtypes, sucb as muscle-relatedTMD, according to the presence or absence ofclinical features. Pain or ache in tbe jaw, temples,face, preauricular area, or inside the ear at rest orduring function, in combination witb tenderness topalpation of 3 or more of 20 palpation sites withat least 1 of the sites being on the same side as thecomplaint of pain, must be present to be diagnosedas TMD. Altbough a categorical classification sys-tem works well if discrete clinical features areavailable, limitations become apparent for symp-toms and signs that recur in more than 1 class orsubset.

The need for additional axes for the classifica-tion of muscle-relared TMD arises from the factthat pain is a multidimensional experience. In thisrespect, pain intensity, affect, and pain-related dis-ability are captured on a second axis in theRDC/TMD, which happens to be a controversialfeature because, based on the line of questions,patients often assume that the provider thinks thatthe problem is in the patient's head. However,information on the affective-motivational meaningof pain and its impact provides information on thecentral state and offers valuable data for the man-agement of selected features. It should also preventthe unsuccessfully managed case from beingtreated with methods that are more appropriatefor acute pain than persistent pain.

Muscle Pain

Terms such as analgesia, referred pain, allodynia,and hyperalgesia are often used in the context ofclinical descriptions of deep somatic and visceral

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pain states. Analgesia refers to the absence orreduced pain experience of a normally painfulstimulus. Referred pain represents pain that iseither adjacent to, or at a distance from, tbe site ofits cause. According to the International Associ-ation for the Study of Pain, byperalgesia refers tothe state of increased pain responsivity to a stimu-lus that is normally perceived as painful, whileallodynia describes the state in which pain is per-ceived in response to a stimulus that is normallynot painful,-•'•' Hyperalgesia and allodynia oftencoexist, and in the context of acute pain they areunderstood to have survival value by amplifyingprotective reflexes and promoting immobilizationafter injury," Pain referral, allodynia, and byperal-gesia also constitute the dominant clinical featuresof persistent muscle pain states; however, theirpurpose IS unclear.

With respect to muscle pain, temporal and spa-tial aspects of pain need to be distinguished.Persistent forms are more likely encountered in aclinical context because of their obvious impact onpatients. Chronic (muscle) pain contains an ele-ment of permanency, as reflected in rhe explana-tory expressions used by many authors, eg, "for along period," "prolonged period," "a long timecourse," or "ongoing/never-ending," In thisrespect, chronic muscle pain, by implication andby its very nature, is either extremely resistant totreatment or never completely relieved. Pain isoften described as "aching," "right," "throbbing,""tender," "exhausting," or "nagging" and isknown to fluctuate in intensity over time.However, the sensory and affective meaning ofpersistent muscle-related TMD pain does notrequire montbs to develop, E.xperimentallyinduced and maintained bilateral masseter musclepain exbibits indistinguisbable sensory and affec-tive properties from the clinical correlate ofchronic pain.^* With the unclear boundarieshetween acute and persistent pain and the under-standing that different treatment approaches arerequired for the 2 conditions, it is left to the clini-cian to make a guess without a validated approachm place that facilitates reliable and useful decision-making.

As far as the spatial distribution of pain is con-cerned, there is a wide range that satisfies theRDCyTMD. Local forms exhibit muscle pain lim-ited to trigeminal dermatomes, while regional pre-sentations demonstrate the additional involvementof cervical dermatomes. Patients with widespreadpain report additional muscle pain in locationsother than the head, neck, and shoulder, and aportion of these patients fulfill the diagnostic crite-

ria of FMS, Comparisons between groups ofpatients with FMS, widespread myalgia, orregional myalgia show that unspecific symptoms,such as sleep disturbance, subjective swelling,intolerance to cold and exercise, and self-report ofa worsening pbysical condition, are more prevalentin FMS than in the others,''

Regional pain distributions can be conceptual-ized by mechanisms responsible for the radiationand spread of pain, such as (Í) branching of pri-mary afferent neurons in the periphery, (2) theconvergence of superficial and deep inputs ontothe same projection neurons, and (3) central neu-roplastic changes that occur with continued noci-ceptive barrage. For beterotopic pam, mostauthors assume that dysregulation of anti-nocicep-tive systems is responsible for a generalized height-ened pain experience. However, the heterotopicpain presentations are not easily explained by thedistribution of terminations of the anti-nociceptivesystem at trigeminal and spinal levels. Peripheralsensitizing mechanisms must likely be contributoryto the pathogenesis of heterotopic pain distribu-tions, given the strong predilection of particularmuscle groups.

Tenderness to Palpation

If pain on palpation is a key component in theassessment of muscle-related TMD and relatedmuscle pain conditions, it is essential to followprotocol to ensure reproducible and reliable mea-surement. The examiner should keep in mind thatdiagnostic assignment is probabilistic and based oncounts of pressure-pain reports at specified sites ofmeasurement. As far as the TMD are concerned,palpation sites are clearly specified in theRDC/TMD. For FMS, the American College ofRbeumatology criteria describe the examinationsites as well. Fxaminers are instructed in theRDCn'MD to use the fingertips of tbe index andthird fingers (or the spade-like pad of the distalphalanx of the index finger only) to press on spe-cific muscle sites with 2 lbs. of pressure and withthe muscle in a relaxed state. The patient isrequested to indicate whether the palpation hurtsor whether he or she simply feels pressure. If ithurts, he or she is asked to report whether thepressure-pain is mild, moderate, or severe. Duringpalpation, the opposite hand should brace thehead to provide stability.

The examiner should be reminded that a moregeneral lowering of thresholds at non-painful sitesparallels pressure allodynia observed at sites ofspontaneous pain in FMS.^^ Lowered pressure-


Stohler

pain thresholds do not seem to be limited to mus-cle, at least in FMS. Skin-fold tenderne.ss and pres-sure-pain thresholds over bone are lower in FMSpatients than in controls, and the phenomenon isobserved irrespective of whether or not sponta-neous pain is felt at the examination s i te ."Unfortunately, data on myofascial pain condi-tions, including the muscle-related TMD, areinconclusive on this subject. However, it appearsthat generalized pressure-pain sensitivity extend-ing beyond the site of painful involvement is notpresent.

Changes in Motor Function

Pain has general effects on motor function, includ-ing changes in facial expression and body postureand a tendency to avoid movements or to performthem more slowly. Pain also lowers the ability towork against heavy loads and makes it difficult tomove quickly. The biologic advantages are obvi-ous. The inability to contract muscles forcefullyand rapidly limits further damage to the body,while the typical facial expressions and gestures ofpain are signals to others that the person is inpain, is suffering, and is in need of help and sym-pathy.*"

The control of muscles of the painful body partis affected in specific ways that are probably notdependent on the type of tissue in which painarises. The activity of the agonist muscles is dimin-ished, while the antagonist become slightly moreactive.^" Heavy pressure on the periosteum of thezygoma reduces the frequency, amplitude, andvelocity of mastication caused by electrical stimu-lation of the corticobulbar tracts of decerebraterabbits.^' Pain-induced changes in mandibularposture form the basis for the patient's perceptionof being disturbed by teeth not fitting togetherproperly. ^

Changes in Mood

The sustained mood change constitutes the symp-tom; affect describes the observable sign associatedwith a particular state of mood. Cognitive andmotivational changes are reflected in the patient'sthoughts; a change in the overall emotional state isexpressed in the subject's mood. By the very natureof chronic conditions to he of long and continuousduration, and because current treatments leavemuch to be desired, interruption in lifestyle is oftenunavoidable." Changes in mood are not surpris-ing, given the fact that patietits with persistentpain recognize that their current quality of life is

much iower than it was. Anger, frustration, fear,sadness, tension, worry, and irritability constitutethe most prevalent negative mood types in persis-tent and severe pain. ''-^^ Symptoms of depressionare numerous and include changes in appetite,sleep disturbances, weight variations, decreasedsexual drive, anxiety, loss of interest, and/ordecreased ability to concentrate.

Women are much more vulnerable ro mood dis-orders and are twice as likely as men to developdepression. The significance of sex differences interms of emotionality and neuroendocrine andautonomie function becomes clear when examin-ing the distribution of estrogen receptors in thebrain. The highest densities of estrogen receptorsare observed in areas that are involved in shapingthe pain response, such as the amygdala, pituitarygland, and hippocampus.^^ The vulnerability ofwomen to greater severity and persistence of painneeds to be better understood in the context of themodulatory effect of female hormones exertingtheir effect at various levels of the CNS, as well asin peripheral tissues.

Conclusions

The clinical features of the muscle-related TMD,such as tenderness to pressure applied to muscle,limited range of mandibular motion, perceivedchanges in the dental occlusion, and mood alter-ations, can be explained as direct consequences ofpain. The mechanisms underlying the pathogenesisof these symptoms and signs include (1) sensitiza-tion of peripheral tissues, (2) neuropiasticity inpro-nociceptive and anti-nociceptive circuits, and(3) the behavioral sensitization associated withincreased emotionality and with pain-specific neu-roendocnne and autonomie responsivity. It is thedifferential contribution of these mechanisms thatcan explain the significant variation in individualcase presentations. The increased vulnerability ofwomen in terms of prevalence, and the severityand persistence of muscle-related TMD pain, couldbe accounted for by the modulatory effects offemale hormones acting on these pain responsesystems.

Acknowledgment

This work was supported by ROl N1DCR-DE1205Í"Pathogenesis of TMD Myalgia Symptoms."


Stohler

References

1. Dworkin SF, LeResche L. Research Diagnosiií Criteria forTemporomandibula r Disorders; Review. Cr i re r i j ,Examinations and Specifications, Critique, J Cranio-mandib Disord Facial Oral Pain 1992;6;301^3J.S,

2. Huggins KH. Dworkin SF, Saunders K, Von Korff M,Barlow W. Five-year course for temporomandibular disor-ders using RDC/TMD [abscracl|, J Dent Res i996;75:352,

3. Tgrp JC."Kowalski CJ. Scohler CS. Temporoniandibulardisorders—Pain outside the head and face is rarelyacknowledged in the cbief complaint, J Prosther Dent1997i 78^592-595,

4. Turp JC, Kowalski CJ. O'Leary TJ. Srohler CS. Pain mapsfrom facial pain patients indicate a broad pain geography.J Dent Res 1998;77:1465-1472,

5. Travell JG, Simons DG, Myofascial Pain and Dysfunction,The Trigger Point Manual, The Upper E\-iremities. vol 1,Baltimore; Williams & Wilkins. 1983,

6. Wolfe F. Smythe H.\. Ygnus MB. Bennett RM, Bombar-dier C. Coldenberg DL, er al. The American College oíRheumatology 1990 Criteria for the Classification ofFihromyalgia. Report of the Multicenter CriteriaCommitiee. Anhritis Rhenm 1990;33:160-172.

7. Wolfe F, Ross K, Anderson J, Russell IJ, Hehert L. Theprevalence and characterisrics of fibromyalgia in ¡he gen-eral population. Arthriris Rheum 1995;38;19-28.

S.Aaron LA. Bradley LA, Alarcon GS. Alexander RW,Triana-Alexander .M, Martin MY. Alberts KR, Psychiatricdiagnoses in patients with fibromyalgia are related tohealrh care-seeking behavior rather than to illness.Arthritis Rheumarism 1996i39:436^45.

9. Goldenberg DL, Management of fibromyalgia syndrome.Rheum Dis CIm North Am I989;15:499-512,

10, Plesh O. Wolfe F. Lane N. The relationship betweenfibromyalgia and [emporomandibular disorders:Prevalence and symptom severity. J Rheumatol1996^23:1948-1952.

11. He den berg-Magnusson B, Ernberg M, Kopp S. Symptomsand signs of temporomandibular disorders in parients withfibcomyalgia and local myalgia of thi temporomandibularsystem. A comparative study. Acta Odoncoi Scand1997:55:344-349.

il. Korsiun A, Papadopoulos E. Demitrack M, Engleberg C.Crofford L. The relarionship between temporomandibulardisorders and stress-associated syndromes. Oral Surg OralMed Oral Pathol Oral Radiol Endod 1998;86:416-^20.

13. Headache Classification Committee of the InternationalHeadache Society. Classification and diagnostic criteria ofheadache disorders, cranial neuralgias and facial pain,Cephalalgia 198S;Sd-96.

14. Unruh AM, Gender variations in clinical pain experience|review¡. Pain 1996;65:123-167,

15. Agerberg G, Carlsson GE, Functional disorders of rhemasticatory system, II, Symptoms in relation to impairedmobiliti' of the mandible as judged from investigation byquestionnaire. Acra Odonrol Scand 1973;31:337-347.

16. Magnusson T. Carlsson GE, Changes in recurrentheadaches and mandibular dysfunction after various typesof dental t reatment . Acta Odonto l Scand 1980;38;311-320,

17. Forssell H. Kangasniemi P, Mandibular dysfunction inpatients with migraine, Proc Finn Dent Soc 1984^80:217-222,

18. Forssell H. Kangasniemi P. Mandibular dysfunction inparients with muscle contraction headache. Proc FinnDent Soc 1984;80r211-216.

19. Hiltunen K. Schmid t-Kaunisaho K, Nevalainen J, Narhi T,Ainamo A, Prevalence of signs of remporomandibular dis-orders among elderly inhahitants of Helsinki. Finland.Acta Odontol Scand 1995^53:20-23.

20. Von Korff M, Dworkin SF. Le Resche L, Kriiger A, Anepidemiologic comparison of pain complaints. Pain19S8;32:173-183.

21, Von Korff M. Wagner EH, Dworkin SF. Saunders KW.Chronic pain and use of ambulatory health care.Psychosom Med 1991;53:61-79.

22, LeResche L. Saunders K, Von KM, Barlow W, DworkinSF, Use of exogenous hormones and risk of temporo-mandibular disorder pain. Pain 1997:69:153-160.

23, Solberg WK, Woo MW, Houston JB, Prevalence ofmandibular dysfunction in young aduits. J Am Dene Assoc

24 Riolo ML, Brandt D, Ten Have TR, Associations betweenocclusal characteristics and signs and symproms of TMJdysfunction in children and young adults. Am J OrthodDentofadal Orthop 1987;92:467--177.Pilley JR. Mohhn B. Shaw WC, Kingdon A. A survey ofcraniomandibniar disorders in 800 15-year-olds. A follow-up study of children with nialocclusion. Eur J Orthod1992;14:152-I6I.List T, Dworliin SF. Comparing TMD diagnoses and clini-cal findings at Swedish and US TMD centers usingresearch diagnostic criteria for temporomandibular disor-ders. J Orofac Pain 1996;10:240-253.Lipton J.^, Ship JA, Larach-Robinson D, Estimated preva-lence and distribution of reported orofacial pain in theUnited States. J Am Dent Assoc 1993;I24:115-121.Pellegrino MJ. Waylonis GW. Sommer A. Familial occur-rence of primary fibromyalgia. Arch Phys Med Rehabil1989;70:61-63.Lesch KP, Bengel D. Heils A. Sabol SZ. Creenberg BD,Petri S, et al. Association of anxiety-related traits with apolymorphism in the serotonin transporter gene regula-tory region. Science 1996;274; 1527-1531.Sessle BJ, The neural basis of temporomandibular joint andmasticatory muscle pam, J Orofat Pam 1999; 13:238-245.Schaible HG, On the role of tachykinins and calcitoningene-related peptide in the spinal mechanisms of nocicep-tion and in the induction and maintenance of mñamma-tion-evoked hyperexcitahility in spinal cord neurons (withspecial reference to nociception in ioinrs| (review!, P™gBrain Res 199ë;113:423-441.Kinnman E, Levine JD. Involvement of the sympatheticpostganglionic neuron in capsaicin-induced secondaryhyperalgesia in the rat, Neuroscience 1995;65:283-291,Schäfer M, Carter L, Stein C lnterleukin-1 beta and corti-cotropin-releasing factor inhibit pain by releasing opioidsfrom immune cells in inflamed tissue. Proc Nari Acad SeiUSA 1994;91:4219^223.Przewlocki R, Hassan AH, Lason W, Epplen C. Herz A.Stein C. Gene expression and localization of opioid pep-tides in immune cells of inflamed tissue: Functional role inantinociception. Neuroscience 1992;48:491-500.Andreev NY. Dimitricva N, Koltzenhurg M, McMahonSB, Peripheral administration of nerve growth factor inthe adult rat produces a thermal hyperalgesia that requiresthe presence of sympathetic post-gangl ionic neurons. Pain1995;63:109-115.


Stobler

36. Lewin GR, Rueff A, Mendell LM, Peripheral and tentralmechanisms of NGF-induced hyperalgesia. Hur J Neurosci

37, Aloe L, Skaper SD, Leon A, Levi-Montakini R. Nervegrowth fattor and au toi mm une diseases. An Co i m m unity.

.Î8, Perry BG, Cornblath DR, Adornaro BT, Cbaudbry V, 52,Fkxner C, Wacbsman M, cl al. The effect of systemicallyadministered recombinani human nerve growth factor inhealtby human subjects, Ann Neurol 1994;36:144-24É, 53.

39. Sohrabji F, Miranda RC, Toran-Allerand CD, Estrogendifferentially regulates esrrogen and nerve growth factorreceptor mRNAs in adult sensory neurons, J Neuruiti 54,1994;Í4:459-A7\.

40. Woolf CJ, Walters ET, Common patterns of plasticity 55,contributing to tiociceptive sensirization in mammals andaplysia. Trends Neurosci 1991;14:74-78,

41. Sessle BJ, Hu JW, Amano N, Zhong C, Convergence of 56,cutaneous, tootb pulp, visceral, neck and muscle afférentsonto nociceptive and non-nocicepiive neurones in trigemi-nal subnucleus caudaiis ¡medullary dorsal horn) and irs 57,implications for referred pain. Pain 1986;27:2I9-235,

42. Russell IJ, Orr MD, Litrman E, Vipraio GA, Alboukreli D,Michalek JE, er al. Elevated cerebrospinal fluid ievels ofsubstance P in parienrs ivirh the fibromyalgia syndrome, 58,Arthriris Rbeum 1994;37;1593-1601.

43. Mense S, Hobeisel U, Reinert A, The possible role of sub- 59,stante P in eliciting and modulating deep somatic pain[review]. Prog Brain Res 1996;110:125-135,

44. Ruda MA, Dubner R, Molecular and biochemical evenrsmediate neuronal plasticity following inflammation and 60.hyperalgesia. In: Willis WD Jr (ed), Hyperalgesia andAllodynia. New Yorki Raven Press, 1992;3] 1-325,

45. Hu JW, Yu XM, Vernon H, Sessle BJ, Excitatory effectson neck and jaw muBcle activity of inflammatory irritant 61.applied to cervical paraspinal tissues. Pain 1993;55:243-250,

46. Hobeisel U, Sander B, Mt:nse S, Myositis-induced func-tional reorganisation of the rar dorsal horn: Effects of 62,spinal superfusion witb antagonists ro neurokmin and glu-tamate receptors. Pain 1997;Ê9:219-230, 63,

47. Gracely RH, Dubner R, McGrath PA, Narcotic analgesia:Fentanyl reduces the intensity but not rhe unpleasantnessof painful rootb pulp sensations. Science 1979; 64,203:1261-1263,

4S. Levine JD, Gordon NC, Jones RT, Fields HI,, The nar-cotic antagonist naloxone enhances clinical pain. Nature 65,197S;272:826-827,

49, Gracely RH, Dubner R, Wolskee PJ, Deeter WR, Placebo 66,and naloNone can alter post-surgical pain by separatemechanisms. Nature i9S3;306:264-265,

Sbarma HS, Nyberg F, Olsson Y, Dey PK, Alteration ofsubstance P after trauma to rhe spinal cord: An experi-mental study in the rat. Neuroscience 1990;3B:205-212,Eide PK, Hole K, Interactions between serotonin and sub-stance P in tbe spinal regulation of nociception. Brain Res19i'l;550;225-230,Almay BG, Jobansson F, von Knorring L, Le Grèves P,Terenius L, Substance P in CSF of parients with cbronicpain syndromes. Pain 1988;33:3-9,Layzer RB, Muscle pain, cramps, and fatigue. In: EngelAG, Franzini-Armstrong C (eds). Myology: Basic Clinical,ed 2. New York : McGraw-Hill, 1994:1754-1768,Merskey H, Pain terms: A current list with definitions andnores on usage. Pain 1999;82iS216-S221,Casey KL, Nociceptors and tbeir sensitization. In: WillisWD (ed], Hyperalgesia and Allodynia. New York: RavenPress, 1992:13-15,Stohler CS, Kowalski CJ, Spatial and temporal summationof sensory and affective dimensions of deep somatic pain.Painl999;79tl65-173,Jacobsen S, Perersen IS, Danneskiold-Samsoe B, Clinicalfeatures in patients wirb chronic muscle pain—witb spe-cial reference to fibromyalgia. Scand J Rbeumarol1993;22:69-76,Tunks E, Crook J, Norman G, Kalaher S, Tender points infibromyalgia. Pain 1988;34:ll-]9,Mikkelsson M, Latikka P, Kauriainen H, Isomeri R,Isnmaki H, Muscle and bone pressure pain threshold andpain tolerance in fibromyalgia patients and controls. ArchPhys Med Rehübil 1 992;73:S14-S1S,Lund JP, Donga R, Widmer CG, Stobler CS. Tbe pain-adaptation model: A discussion of the relationshipberween chronic musculoskeleral pain and motor activity.Can J Physiol Pbarmacol 1991;69^683-694.Scbwartz G, Lund JP, Modification of rbytbmical jawmovements by noxious pressure applied to the periosteumof the zygoma in decerebrate rabbi ts . Pain 1995;63:153-161,Obrez A, Stohler CS. Jaw muscle pain and its effect ongothic artb tracings. J Prosther Dent 1996;75:393-398,Von Korff M, Ormel J, Katon W, Lin EH, Disability anddepression among higb utilizers of bealrb care, A longitu-dinal analysis. Arcb Gen Psych 1992;49:91-100,Fernandez E, Mil burn T ^ , Sensory and affective predic-tors of overall pain and emotions associated witb affectivepain, ClinJ Pain 1994;10:3^9,Sofaer B, Walker J, Mood assessment in chronic painpatients, Disabil Rehabil Í994;16:35-3S.Simerly RB, Chang C, Muramatsu M, Swanson LW,Distribution of androgen and estrogen receptor mRNA-conraining cells in rbe rat brain: An in sim bybridizationstudy, J Comp Neurol 1990;294t76-95,

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