A meta-analytic study of experimental and chronic orofacial pain excluding headache disorders

Abstract

Chronic orofacial pain (COFP) disorders are prevalent and debilitating pain conditions affecting the head, neck and face areas. Neuroimaging studies have reported functional and grey matter abnormalities, but not all the studies have reported consistent findings. Identifying convergent abnormalities across COFPs provides a basis for future hypothesis-driven research aimed at elucidating common CNS mechanisms. Here, we perform three coordinate-based meta-analyses according to PRISMA guidelines to elucidate the central mechanisms of orofacial pain disorders. Specifically, we investigated consistent patterns of: (1) brain function to experimental orofacial pain in healthy subjects, (2) structural and (3) functional brain abnormalities in COFP. We computed our coordinate-based meta-analyses using GingerALE. The experimental pain meta-analysis revealed increased brain activity in bilateral thalami, posterior mid-cingulate cortices, and secondary somatosensory cortices, the right posterior parietal cortex extending to the orofacial region of the right primary somatosensory cortex and the right insula, and decreased activity in the right somatomotor regions. The structural COFP meta-analysis identified consistent higher grey matter volume/concentration in the right ventral thalamus and posterior putamen of COFP patients compared to healthy controls. The functional COFP meta-analysis identified a consistent increase in brain activity in the left medial and posterior thalamus and lesser activity in the left posterior insula in COFP, compared to healthy controls. Overall, these findings provide evidence of brain abnormalities in pain-related regions, namely the thalamus and insula, across different COFP disorders. The convergence of thalamic abnormalities in both structure and function suggest a key role for this region in COFP pathophysiology.

Keywords: Brain; Facial pain; Grey matter volume; MRI; Orofacial pain; Pain; Plasticity; Trigeminal; VBM; fMRI; sMRI.

Fig. 1

Article selection for functional studies. Flow diagram according to PRISMA guidelines for functional MRI article selection procedures.

Fig. 2

Article selection for structural studies. Flow diagram according to PRISMA guidelines for structural MRI (grey matter) article selection procedures.

Fig. 3

(A) Significant ALE effects of functional MRI studies of healthy subjects during experimental orofacial pain. The functional MRI meta-analysis in healthy subjects identified significant ALE effects in bilateral thalami, bilateral posterior mid-cingulate cortex (pMCC) and bilateral secondary somatosensory cortices (S2), the right PPC extending to the primary somatosensory cortex (S1), the right insula and the primary motor cortex (M1) in healthy subjects during experimental pain (Exp.) (cluster-corrected p < .05 and cluster-forming threshold of p < .005). (B) Axial slices of thalamic activity in healthy subjects during experimental orofacial pain. Thalamic activation cluster from the meta-analysis of experimental studies (cluster-corrected p < .05, cluster-forming threshold p < .005).

Fig. 4

(A) Significant ALE effects of structural COFP studies. The structural MRI (grey matter) COFP meta-analysis identifies structural GMV/GMC increase in the right thalamus and putamen in COFP patients compared to healthy subjects, significant at p < .05 (cluster-corrected, cluster-forming threshold of p < .005). (B) Axial slices of structural thalamic abnormalities in COFP patients. Representation of the thalamic activation cluster from the meta-analysis of structural chronic pain studies (cluster-corrected p < .05, cluster-forming threshold p < .005).

Fig. 5

(A) Significant ALE effects of functional COFP studies. The functional MRI COFP meta-analysis identified significant ALE effects in the left posterior thalamus and left posterior insula of COFP patients compared to healthy controls, significant at p < .05 (cluster-corrected, cluster-forming threshold of p < .005). (B) Axial slices of functional thalamic abnormalities in chronic orofacial pain patients. Thalamic cluster from the meta-analysis of functional MRI COFP studies (cluster-corrected p < .05, cluster-forming threshold p < .005).