Appendix

"The Equivocal Results and Misleading Conclusions in Current Research addressing TMD / Orofacial Pain"

James L. Guinn, D.M.D.

March 3, 2009

 

In the forward to the new text “Orofacial Pain & Headache” edited by Sharav and Benoliel1, Dr. Barry Sessle states:  “A patient with orofacial pain can represent a significant challenge to the clinician, leading to repeated and usually unsuccessful interventions.”  He goes on:  “To further complicate matters, pain is a multidimensional experience involving physical, cognitive and emotional aspects and chronic pain in particular recruits active involvement of these dimensions…The trigeminal nerve innervates anatomically related but functionally diverse organs such as the meninges, the craniofacial vasculature, the eyes, the ears, the teeth, oral soft tissues, muscles and the temporomandibular joint.  In the brainstem, the trigeminal sensory nucleus overlaps with upper cervical dermatomes.  Taken together, these features account for the complex and extensive pain referral patters that often make clinical diagnosis so difficult.”

What is the reason for the “repeated and usually unsuccessful interventions” in this field?

Sessle’s observation that TMD/OFP patient treatment is characterized by “repeated and usually unsuccessful interventions,” goes hand in hand with the results of most clinical trials.  Specifically, there has, so far, been no robust treatment intervention demonstrated in RCT’s or their associated systematic reviews.  Given the equivocal results from research on potential treatment interventions in TMD/OFP, one has to ask the question: “Are the intervention results equivocal because the studied treatment lacks efficacy, or because of failure(s) in differential diagnostic methods and the resulting inappropriate inclusion/exclusion criteria employed in the trial?”  In other words, are the results of clinical trials on various treatment modalities an indictment against the treatment, or an indication of weak trial design and methodologies?

The Handicap of a Syndrome

A syndrome refers to the apparent association of several clinically recognized features (signs), symptoms, or characteristics that often occur together, so that the presence of one feature alerts the clinician to the presence of the others.  These signs or symptoms collectively indicate or characterize a disease or abnormal condition.  The term syndrome derives from the Greek, and means literally “runs together.” 

The corollary to the term syndrome is the implication that a standard treatment regimen or protocol exists which will resolve the condition(s).

The problem with labeling a collection of signs and symptoms a syndrome is that it can potentially impede sound scientific investigation, as well as mislead and frustrate clinicians and patients alike.

It is generally recognized that the term “TMJ Syndrome” is no longer appropriate.  However, the functional working hypothesis of most randomized controlled trials and systematic reviews in this field are, in fact, based on this naive premise.  Standard phrases utilized in a description of the “problem” to be studied include the following:  “In patients with temporomandibular disorder…”;  “In patients with myogenous orofacial pain…”;  “In patients with myofascial pain dysfunction syndrome…”.  This leads to inclusion criteria such as the following:  “80 consecutive patients seen in a university TMD clinic,” “mandibular dysfunction”, “TMJD”, “facial pain”, and “CMD”.

This “misdirection” in clinical trials is summarized in a systematic review authored by Forssell, et al.2:  “The actual definitions of the patient samples varied.  The study population was described to consist of TMD (or alike) patients, and patients with muscle pain and different types of joint problems were placed into a single group.  However, the distinct clinical entities that constitute TMD are likely to exhibit differences in treatment responses.  Trials using more detailed case definitions would probably be more sensitive and give more clinically useful information.”

This problem is compounded by some researchers who appear to lack a fundamental understanding of the subject they are studying.  One systematic review recently published on myofascial pain3 states:  “A diagnosis of myofascial pain can be made if the patient exhibits more than one of the following signs and/or symptoms in any combination:  Pain on palpation of the temporomandibular joint; Pain on palpation of associated mandibular muscles; Limitation and/or deviation of mandibular movement; Joint sounds and headache.”  Even the reference to mandibular muscles may not apply in this case, because in myofascial pain the site of the pain is not the source of the pain.

Headache is a common co-morbidity in the field of TMD/OFP.  It shares many of the same contributing factors and pathophysiology.  Like TMD/OFP, headache is a multifactorial condition.  Yet headache, in all its forms, has been systematically studied with great success, based on an internationally accepted classification system.  This system is published and continually updated by the International Headache Society (IHS), chaired by Dr. Jess Olesen.  In this classification system, each component of headache is described and defined with great specificity, using unequivocal terms4.  Unfortunately, no such system exists for TMD/OFP.

The Answer

The answer to equivocal TMD/OFP interventions for both clinicians and researchers is to abandon the mindset of a syndrome.  In the field of TMD/OFP, there is no substitute for making a thorough differential diagnosis, based on the following.

History

A detailed history from the patient, including:

Family history

Trauma history (including a history of hyperemesis and childhood injuries), Surgery history (including the total number of intubations)

Physical/sexual abuse

The chronicity of the symptoms, including the sequence in which they appeared

The quality of the pain

Exacerbating and attenuating features

Whether use of the jaw exacerbates the symptoms

Screening instruments to assess psychological factors

Previous treatment

Medication history, evidence of medication overuse and dependence

Sleep quality and quantity, as well as sleep posture

Diet and exercise history

Work/home environment

 

Clinical Exam

  • Pain on palpation throughout the head, neck, and jaw

  • Range of motion measurements, with deviation & deflection noted

  • Jaw provocation tests

  • Evaluation of potential trigger points in the head, neck, and jaw, with their pain referral patterns

  • Objective evidence of:

  • Crepitation

  • Subluxation

  • Capsulitis or joint effusion

  • Parafunction

  • Severe malocclusion (orthopedic instability)

  • Odontogenic etiology for the pain

  • Autonomic features

  • Coronoid tendonitis

  • Cervical myofascial referral to the jaw

  • Carotidynia or temporal arthritis

  • Facial migraine

  • Bulimia or GERD

 

Radiographic Examination

  • Condylar degeneration, resorption, or other morphologic changes

  • Developmental deformities

  • Previous fracture or orthognathic surgery

  • Sinus mucosal inflammation or sinusitis (for CT)

  • Coronoid hypertrophy or impingement

 

Structural contributing factors

  • Hypermobility syndrome or damaged joint ligaments

  • Marfans or Ehlers-Danlos syndrome

  • Evidence or history of collagen-vascular diseases

  • Disc displacement with or without locking

  • Developmental deformities

  • The use of certain CPAP Masks

  • Stylo-hyoid calcification

  • Coronoid adhesions

 

Neuromuscular Contributing Factors

  • Parafunction (clenching, bruxism, muscle bracing)

  • Adverse events from medications (SSRI’s, SNRI’s, amphetamines)

  • Obstructive sleep apnea

  • Tongue thrust

 

Neuropathic Contributing Factors

  • Static or dynamic allodynia, hyperalgesia

  • Quality of pain consistent with neuropathy

  • History of onset with failed dental treatment or nerve damage

  • Central sensitization or up-regulation

  • Complex regional pain syndrome

 

Psychological Contributing Factors

  • Anxiety

  • Depression

  • Somatization

  • Insomnia

  • OCD

  • Borderline personality disorder

  • Poor “coping” mechanisms

  • Demanding lifestyle (work, school, family)

  • Malingering

  • Secondary Gain

  • PTSD

 

Associated Co-Morbidities

  • Migraine

  • TT Headache

  • Cervicogenic Headache

  • Fibromyalgia

  • Cervicalgia

  • Osteochondritis Dessicans

  • Orofacial Dyskinesia

  • Chiari Malformation

  • Unresolved sinus disease

  • Ankylosing spondylitis

  • Systemic Arthritis

 

Because every patient will present with a different combination of history, clinical findings, contributing factors, and co-morbidities, trying to test the efficacy of any one treatment modality on this entire population is foreordained to equivocal results, whether it is employed in a clinical trial or by a treating clinician.  Failure to recognize all of these factors can have unintended consequences for research and for patients undergoing treatment.  Furthermore, even if the diverse combinations of contributing factors and co-morbidities are recognized by researchers, attempts to control for all these contributing factors have proven to be very challenging.

It is a disservice to patients and to scientific inquiry to continue to publish equivocal results and to draw conclusions from these results, based on the methods currently employed in trials and systematic reviews addressing TMD/OFP.  While such trials may appear to be “evidence-based”, a closer inspection of the subject being investigated, the inclusion and exclusion criteria, the lack of adequate controls, and the overall quality of the trial leads one to the conclusion that the results could have been predicted.

For too many years, clinicians have tried to make their patients fit the limited treatment modalities they are familiar with, often with little thought for the etiology and contributing factors for any particular patient.  Current research only perpetuates this application of a particular treatment to broad section of the general population labeled as having “TMJ.”  It is inevitable that the result will be the state of futility described so well by Dr. Sessle above.

In his book How Doctors Think5, Dr. Jerome Groopman states “Misdiagnosis is a window into the medical mind.  It reveals why doctors fail to question their assumptions, why their thinking is sometimes closed or skewed, why they overlook gaps in their knowledge.  Experts studying misguided care have recently concluded that the majority of errors are due to flaws in physician thinking, not technical mistakes.  In one study of misdiagnoses that caused serious harm to patients, some 80 percent could be accounted for by a cascade of cognitive errors, often putting the patient into a narrow frame and ignoring information that contradicted a fixed notion.”

In order to achieve predicable results with any TMD/OFP intervention, it is imperative to identify the key diagnoses, contributing factors, and co-morbidities.  Only then can a meaningful intervention be tested on a subset of patients with highly correlated, well-defined features in a clinical trial. 

For treatment of individual patients, a multidisciplinary approach is often necessary in order to effectively address that patient’s principle precipitating and perpetuating factors.  It should therefore not be surprising that a clinical trial, which lacks such an approach, will produce equivocal results.

 

References

1.         Yair S., Rafael B., eds, Orofacial Pain & Headache, Mosby, 2008

2.         Forssell, Heli, et al., Application of Principles of Evidence-Based Medicine to Occlusal Treatment for Temporomandibular Disorders, J. Orofacial Pain, Vol 18, No 1, 2004, pp 9-32

3.         Al-Ani, Ziad, et al., Stabilization Splint Therapy for the Treatment of Temporomandibular Myofascial Pain:  A Systematic Review, J Dental Education, Vol 69, No 11, 2005, pp 1242-1250

4.         http://ihs-classification.org/en/

5.         Groopman, J., MD, How Doctors Think, Houghton Mifflin, pg 24, 2007

 

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