Brain Research Bulletin, 2025/06, 226111375. doi: 10.1016/j.brainresbull.2025.111375, type of study: ,rct,

Free full text   (https://www.sciencedirect.com/science/article/pii/S036192302500187X)

Keywords:

brain [108]
chronic pain [323]
functional connectivity [6]
low back pain [523]
OMT [3924]
osteopathic manipulative treatment [3945]
opioid receptors [1]
randomized controlled trial [947]

Abstract:

BACKGROUND: Osteopathic Manipulative Treatment (OMT) has emerged as a therapeutic approach for chronic low back pain (cLBP). Previous Magnetic Resonance (MR) studies have demonstrated that four weeks of OMT alter resting-state functional connectivity (rs-FC) in the somatosensory cortex, prefrontal regions, and frontal operculum/insula. However, it remains unclear whether a single session of OMT can immediately affect brain rs-FC. METHODS: We combined a data-driven approach with a seed-based connectivity analysis to examine the pattern of whole-brain rs-FC in a cohort of thirty cLBP patients before and after a first acute session of OMT (N = 16) or a sham treatment (N = 14). Correlation analyses were performed to explore the relationship between the resulting rs-FC maps and receptor density/gene expression maps derived from in vivo brain atlases, focusing on the opioid and cannabinoid systems. RESULTS: Data-driven analysis revealed that, compared to the sham group, the OMT increased the intrinsic connectivity of the right dorsolateral prefrontal cortex. Seed-based connectivity analysis showed that this region increased coupling with the right frontal operculum/insula. Notably, no effect of immediate OMT was found in the somatosensory cortex. The topography of these rs-FC changes selectively overlapped with the distribution of mu-opioid receptors. CONCLUSIONS: Acute OMT in cLBP patients modulates rs-FC across cortical regions primarily involved in top-down cognitive control of pain, as well as in integrating pain intensity perception and related expectations. Spatial comparisons between rs-FC maps and receptor atlases suggest that these neural changes involve opioid, not cannabinoid, neurotransmission.