Posted on 14-10-2021

Baseline functional connectivity of key nodes in pain processing and modulation determine subsequent pain ratings of an ecologically valid model of orofacial pain

Neuroimaging studies have identified that individual differences in pain sensitivity are related to structural gray matter differences and functional connectivity between brain regions involved in pain processing. However, experimental pain models in these laboratory studies are limited in ecological validity, as they do not mimic the persistent pain that typically occurs in real-life experiences. UTCSP members Dr. Iacopo Cioffi and Dr. Massieh Moayedi and colleagues investigated whether baseline structure and function of key brain regions involved in ascending and descending pain pathways correlate with subsequent peak pain intensity ratings induced by an ecologically and clinically relevant orofacial pain model.

Baseline structure and functional connections of the periaqueductal gray (PAG), which modulates descending pain, and the thalamus, which is the primary relay site of nociceptive input, were measured in 26 healthy individuals using magnetic resonance imaging. In an orthodontic procedure, an elastomeric separator is inserted and kept between two molars for five days to induce orofacial pain that is mediated by the trigeminal nociceptive system. Participants recorded their pain intensity each day, which peaked within 48 hours and resolved within a week. The authors identified no structural correlates of peak pain intensity, however the resting state functional connectivity (rsFC) of the PAG and thalamus significantly correlated with peak pain ratings: participants with greater baseline thalamo-insular connectivity reported higher subsequent peak pain, whereas participants with greater baseline rsFC between the PAG and default mode network reported lower subsequent peak pain.

The results of this study, published in Pain, suggest that individual differences in functional connectivity in ascending and descending nociceptive networks in the brain can determine the intensity of a subsequent realistic orofacial pain stimulus. These findings provide insight to the role of the PAG and thalamic nodes in pain perception and can be used clinically to predict individual responses to treatments.

To read more about this work, please see:

Ayoub, L.J., McAndrews, M.P., Barnett, A., Ho, J.K.C., Cioffi, I., & Moayedi, M. (2021). Baseline resting state functional connectivity predicts individual pain ratings to a tonic orofacial pain stimulus. Pain, 162.