A Dissociation Between Primary Motor Cortex Reorganization and Correlation with Pain Intensity in Phantom Limb Pain: A Systematic Review of fMRI Studies.

BACKGROUND

Phantom limb pain (PLP) constitutes a diagnostic and therapeutic challenge with an unknown pathophysiology that likely comprises a combination of cerebral, spinal, and peripheral nervous system pathways. A novel therapeutic field in chronic pain targets cortical areas as treatment foci for neuropathic pain. One studied target in phantom limb pain is the primary motor cortex (M1). Given some promising results of noninvasive brain stimulation to reduce PLP, understanding further the role of M1 in the mechanisms of PLP would provide important future insights to further develop this therapeutic target.

OBJECTIVE

To synthesize neuroimaging evidence on M1 reorganization in PLP and evaluate its association with pain intensity.

METHODS

Six databases (Ovid MEDLINE, Cochrane Library, CINAHL, Scopus, Web of Science and EMBASE) were searched.

RESULTS

Of the 2582 articles, 13 articles met our criteria and were included. Evidence demonstrated cortical reorganization in the contralateral M1, characterized by increased activation and maintained functional representation of the absent limb, lasting decades post-amputation. Patients with PLP showed significant activation in M1 and the somatosensory cortex during phantom limb movements, alongside reduced interhemispheric functional connectivity. However, results regarding the relationship between M1 reorganization and PLP intensity were inconsistent.

CONCLUSION

M1 cortical reorganization plays a substantial role in PLP mechanisms, making it a viable therapeutic target. The inconsistent correlation between M1 activity and PLP severity highlights the complexity of PLP pathophysiology. Future research should standardize imaging protocols, control for confounding variables, and investigate interactions between M1 and other brain regions to improve therapeutic approaches.