This month we present the last set of findings from “Act Two” of the Oral Pain: Prospective Evaluation and Risk Assessment (OPPERA) study. [The Journal of Pain, Volume 14, Issue 12, Supplement, December 2013, pp. T1-T124.] Recall that these investigators recruited some 3,000 men and women between 18 and 44 years old who agreed to be studied over several years at four academic sites: Chapel Hill, NC; Baltimore, MD; Gainesville, FL; and Buffalo, NY. All were TMD free at the beginning of the study. The researchers collected a wide range of physiological and psychological data, constituting different “domains,” at the start of the study, hoping they would be able to identify risk factors distinguishing those individuals who developed first-onset TMD from those who did not.
In the final analysis the team had prospective data on 2,737 subjects of whom 260 developed first-onset TMD over a five-year study period. This month we report on findings in two domains.
One domain concerns pain sensitivity and certain autonomic factors governed by the autonomic nervous system (the system that controls vital processes like heart rate and blood pressure). Essentially, do people who develop TMD have a heightened sensitivity to pain to begin with? And what about their heart rate or blood pressure?
The investigators noted that their findings with regard to first-onset TMD are in marked contrast to an earlier OPPERA case-control study comparing TMD-free individuals (the controls) to patients with chronic TMD (the cases). That study found 29 out of 36 measures of experimental pain sensitivity were associated with chronic TMD. The investigators suggest that these additional pain measures may be critical in the transition from acute to chronic TMD.
The second domain concerns genetics: are there genetic factors that predispose individuals to TMD?
In search of genetic answers, OPPERA researchers used DNA purified from blood samples collected from the volunteers. Their highly sophisticated techniques of analysis make use of the fact that there are many minor variations in the genomes of individuals that involve only a single letter change in the genetic code. These “single nucleotide polymorphisms” called “SNPs” (pronounced snips) number in the millions. They are scattered across the genome both within and between genes and can be used to distinguish one genome from another. For example, if individuals with a given disease have a particular SNP at some place in their genomes in contrast to a control group who lack that SNP and who are disease free, researchers can presume that that particular genetic variant is a marker associated with the disease and perhaps can provide a clue of what went wrong.
What the OPPERA investigators did was to narrow their search to look at a set of 3,295 SNPs found in the sequences of 358 genes known to be involved in pain systems to see if any of these SNPs occurred significantly more in people who developed TMD compared to those who did not. No such luck. This was not surprising given the complex causes of TMD, as well as the small size of the sample (the 260 genomes of people with first-onset TMD).
The investigators conclude that this approach, exploring the genomes of “intermediary phenotypes,” meaning individuals who do not have TMD but could be considered in a pre-TMD stage, can be very fruitful. It can point to genes of interest, help to define sub-populations of TMD patients, and provide new targets for drugs to treat these sub-populations.
The TMJA wishes to acknowledge the volunteers whose gracious consent to multiple physical examinations, tests and questionnaires over several years made this study possible. We must also compliment the investigators whose painstaking statistical analyses generated new and noteworthy findings and wish them success as they continue their work. As Dr. Samuel Dworkin wrote in his introduction to the collected papers, “The depth and breadth of the OPPERA project, with much more longitudinal data still to come, make it an important and unique milestone in chronic orofacial pain research, and indeed, in chronic pain research more generally.”
By Joan Wilentz, The TMJ Association
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