Neuroimaging meta-analysis of brain mechanisms of the association between orofacial pain and mastication

Abstract

Background: Temporomandibular disorders (TMD) are characterized by pain and impaired masticatory functions. The Integrated Pain Adaptation Model (IPAM) predicts that alterations in motor activity may be associated with increased pain in some individuals. The IPAM highlights the diversity of patients' responses to orofacial pain and suggests that such diversity is related to the sensorimotor network of the brain. It remains unclear whether the pattern of brain activation reflects the diversity of patients' responses underlying the association between mastication and orofacial pain.

Objective: This meta-analysis aims to compare the spatial pattern of brain activation, as the primary outcome of neuroimaging studies, between studies of mastication (i.e. Study 1: mastication of healthy adults) and studies of orofacial pain (i.e. Study 2: muscle pain in healthy adults and Study 3: noxious stimulation of the masticatory system in TMD patients).

Methods: Neuroimaging meta-analyses were conducted for two groups of studies: (a) mastication of healthy adults (Study 1, 10 studies) and (b) orofacial pain (7 studies), including muscle pain in healthy adults (Study 2) and noxious stimulation of the masticatory system in TMD patients (Study 3). Consistent loci of brain activation were synthesized using Activation Likelihood Estimation (ALE) with an initial cluster-forming threshold (p < .05) and a threshold of cluster size (p < .05, familywise error-corrected).

Results: The orofacial pain studies have shown consistent activation in pain-related regions, including the anterior cingulate cortex and the anterior insula (AIns). A conjunctional analysis of mastication and orofacial pain studies showed joint activation at the left AIns, the left primary motor cortex and the right primary somatosensory cortex.

Conclusion: The meta-analytical evidence suggests that the AIns, as a key region in pain, interoception and salience processing, contributes to the pain-mastication association. These findings reveal an additional neural mechanism of the diversity of patients' responses underlying the association between mastication and orofacial pain.

Keywords: brain; mastication; meta-analysis; neuroimaging; pain; temporomandibular disorders.