Table 1:
Summary of OPPERA Prospective Cohort genetic findings and potential painful TMD aetiological mechanisms37
| Gene | Encodes | Function | Phenotype | Implications |
|---|---|---|---|---|
| SCN1A | Alpha subunit of voltage-gated sodium channel Nav 1.1 | Nav 1.1 is involved in the generation and propagation of action potentials in sensory nerves | Nonspecific orofacial symptoms† | SCN1A has also been associated with short-term memory performance in other studies and may alter somatic sensitivity |
| ACE2 | Angiotensin I–converting enzyme 2 | Angiotensin-related peptides have been suggested to function as neurotransmitters in the periaqueductal grey (PAG) and other brain regions involved in endogenous pain modulation. In addition to angiotensin I, pro and antinociceptive peptides (e.g. bradykinin, substance P, and opioids such as dynorphin and enkephalin) are substrates of ACE2 | Nonspecific orofacial symptoms† | Pharmacologic inhibition of ACE has been associated with increase in nociceptive thresholds and tolerance, and risk of complex regional pain syndrome (CRPS) |
| PTGS1 | Prostaglandin-endoperoxide synthase 1 (COX-1) enzyme | COX-1 catalyses the conversion of arachidonic acid into prostaglandins mediating inflammatory response and regulating neuronal sensitivity to pain | Global psychological symptoms‡ | Could alter somatic sensitivity, awareness of autonomic activity and nociception |
| APP | Amyloid-β precursor protein | APP is expressed by neurons and is involved in synapse formation and neuronal plasticity. May modulate cognitive ability and cognitive aging | Stress and negative affect§ | Increased expression of APP may underlie higher perception of stress |
| MPDZ | Multiple PDZ domain protein (MUPP1) | Scaffolding for G protein–coupled receptors involved in nociception and analgesia (e.g. serotonergic and GABAergic). May also regulate glutamate-related excitatory neurotransmission | Heat pain temporal summation¶ | May be associated with temporal summation of pain through neurotransmitter regulation |
Global psychological symptoms is a composite measure built via principal component analysis, characterized by high loadings from SCL-90R Somatization Scale, Pennebaker Inventory of Limbic Languidness (PILL), and the Lifetime Stressor List/PTSD Checklist–Civilian Version PTSD symptom scale.
Stress and negative affect is a composite measure built via principal component analysis, characterized by high loadings from State and Trait Anxiety, Perceived Stress Scale (PSS), Profile of Mood States–Bipolar (POMS) Negative Affect scale, and Eysenck Personality Questionnaire–Revised (EPQ-R) Neuroticism scale; negative loadings from POMS Positive Affect scale and EPQ-R Extraversion scale.
Nonspecific orofacial symptoms were measured as count of 6 aversive sensations of the face and jaw not described as pain: stiffness, cramping, fatigue, pressure, soreness, and ache.
Heat pain temporal summation is a quantitative sensory test measure of endogenous pain facilitation.