Dysfunctional μ-opioid System in TMD is Modulated by COMT Genotype

Objectives: This study evaluated the brain mechanisms involved in chronic TMD pain by investigating the differences in the μ-opioid system between chronic TMD patients and healthy controls during clinical and experimental masseteric pain. The study also evaluated the relationship between the COMT val¹⁵⁸met genotype and μ-opioid receptor non-displaceable binding potential (μOR BP_ND) in TMD patients, as well as pain tolerance measured by a masseteric pain challenge.
Methods: Twelve chronic TMD patients (DC-TMD: Masticatory myofascial pain classification) and twelve age- and sex- matched healthy controls (HC) participated in this study. After clinical and psychophysical evaluation, participants underwent a MRI and a PET session with [¹¹C]carfentanil (CFN). The GeoPain (MoxyTech LLC), questionnaires, and quantitative sensory testing (QST) were also used to measure sensory and affective pain ratings. The first 45 minutes of the PET scan (early phase) measured baseline receptor binding potential. The last 45 minutes of the scan (late phase) consisted of a 20-minute sustained acute pain challenge induced by injecting 5% NaCl hypertonic saline into the masseter muscle. Moreover, blood samples were collected throughout each PET scan. The participants were genotyped for the different COMT alleles.
Results: There were no differences between chronic TMD patients and HC during baseline. However, TMD patients demonstrated significantly greater reductions in μOR BP_ND in the left parahippocampus during the sustained masseteric pain challenge compared to HC (MNI coordinates x=-16, y=-34, z=-8; p=0.002). The reduction in μOR BP_ND was negatively correlated with chronicity of pain in TMD patients (p-value = 0.03). Regarding COMT analyses, patients and HC with gene variations (val-met/met-met) demonstrated significantly lower μOR BP_ND during the sustained masseteric pain challenge compared to the val158 homozygotes (p-value < 0.05).
Conclusions: These findings suggest dysfunctional endogenous opioid function in the limbic system of chronic TMD patients that are modulated by the COMT 158 met substitution.