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Fig. 2. Jaw muscle, TMJ disc and joint conditions are often not lim-
ited to the domain of the masticatory system and include regional
and widespread complaints not captured in a systematic fashion by
current taxonomies.
Fig. 3. TMJ conditions conceptualized as a complex disease.
A limitation is also the fact that besides pain and the
impairment of jaw motor function, including produce predictable effects on the stress-response
mechanical hindrance to freely gliding movement of system, including the launch of titrated sensory,
the articular components, symptoms, both relevant to affective, neuroendocrine and autonomic messages
patients and the understanding of TMJ diseases as a characteristic for a given subject. The resulting symp-
system response, are not systematically captured by toms should be understood as the person’s complex
any TMJ taxonomy today. Although varying from case- response trait with specific complaints being either
to-case in terms of the magnitude of their expression, amplified or attenuated by the unique genetic makeup
this includes swelling, numbness, sweating and flush- and/or prior experience. Hormonal milieus are
ing, sleep disturbances, cardiovascular and gastroin- believed to augment the inherent genetic vulnerability
testinal complaints, weight loss or weight gain, loss of to TMJ diseases, explaining the greater likelihood of the
libido and reproductive impairment. Unfortunately, condition among women in the childbearing age.
symptoms that fall within the anatomical region of a Whether or not stimulus specificity (e.g. specific insult)
clinician’s specialty continue to receive greater weight is required to cause a clinically distinct presentation, or
than case attributes outside the respective topograph- whether the exaggerated system response itself should
ical domain, reducing the capability to describe TMJ become the focus of clinical attention, remains to be
diseases as a complex systemic system response. seen.
There is some validity in support of this conceptual
framework. When exposed to sustained experimental
Chasing vulnerability alleles pain, applied to masseter muscles and matched in
terms of perceived pain intensity, human subjects’
Individuals are not equally susceptible to disease. For perceptions depends on the individual level of activa-
example, women in their reproductive years represent tion of the endogenous l-opioid system (5). On the
the majority of those seeking care and the extent to other hand, activation of the l-opioid system that
which genetic and epigenetic factors contribute to TMJ shapes the subject’s response is significantly influ-
diseases has become a hot research topic. Besides enced by the catechol-O-transferase (COMT) genotype
familial risks, different genotypes can involve suscep- and linked to distinct traits of pain perception and
tibility to a particular clinical course of the disease and/ brain activation (6).
or treatment response, including the development of The underlying genetic variance of COMT consists
complications (e.g. unfavorable response to environ- of valine-methionine (val/met) substitution at
mental challenge, material, etc.) (Fig. 3). amino acid 108/158 in the soluble or membrane
Following deviation from homeostasis, such as the bound COMT proteins that is linked to a difference
experience of pain, distinct genotypes are expected to in thermo-stability, causing a three- to fourfold
in adult rats in which neonatal tissue was exposed to 7. Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL,
Weinshilboum RM. Human catechol-O-methyltransferase phar-
experimentally induced persistent hind paw inflam-
macogenetics: description of a functional polymorphism and its
mation (20). potential application to neuropsychiatric disorders. Pharmaco-
genetics 1996;6(3):243–50.
8. Strous RD, Bark N, Parsia SS, Volavka J, Lachman HM. Analysis of
a functional catechol-O-methyltransferase gene polymorphism in
Conclusions schizophrenia: evidence for association with aggressive and
antisocial behavior. Psychiatry Res 1997;69(2–3):71–7.
Despite the inability to account for many observations, 9. Grace AA, Gerfen CR, Aston-Jones G. Catecholamines in the
popular theories regarding the etiopathogenesis of TMJ central nervous system. Overview. Adv Pharmacol (New York)
1998;42:655–70.
disease project a false sense of security to the profes- 10. Steiner H, Gerfen CR. Enkephalin regulates acute D2 dopamine
sion. It all boils down to the following quote: ‘It ain’t receptor antagonist-induced immediate-early gene expression in
what we don’t know that gets us into trouble. It’s what striatal neurons. Neuroscience 1999;88(3):795–810.
11. Steiner H, Gerfen CR. Role of dynorphin and enkephalin in the
we do know that ain’t so’ (21). Blessed are those dis-
regulation of striatal output pathways and behavior. Exp Brain
ciplines that embrace scientific discovery with an open Res 1998;123(1–2):60–76.
mind. In this respect, discipline representatives with a 12. Voorn P, Gerfen CR, Groenewegen HJ. Compartmental organ-
critical mind and powerful voice, such as Lysle John- ization of the ventral striatum of the rat: immunohistochemical
distribution of enkephalin, substance P, dopamine, and calcium-
ston for Orthodontics and TMJ, are crucial for the
binding protein. J Comp Neurol 1989;289(2):189–201.
integrity and respect of the dental profession in the 13. Fahndrich E, Coper H, Christ W, Helmchen H, Muller-Oerling-
community of science and health professionals. hausen B, Pietzcker A. Erythrocyte COMT-activity in patients with
affective disorders. Acta Psychiatr Scand 1980;61(5):427–37.
Acknowledgments: The Brotman Pain Center is supported 14. Floderus Y, Saaf J, Ross SB, Wetterberg L. Catechol-O-methyl-
through generous gifts from the families of Drs Don Brotman transferase activity in human erythrocytes: methodological
aspects. Upsala J Med Sci 1981;86(3):309–18.
and Sol Brotman, both great alumni of University of Maryland,
15. Floderus Y, Ross SB, Wetterberg L. Erythrocyte catechol-O-
Dental School. Supported by NIH-NIDCR R01-DE15036 (CSS).
methyltransferase activity in a Swedish population. Clin Genet
1981;19(5):389–92.
16. Boudikova B, Szumlanski C, Maidak B, Weinshilboum R. Human
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