An ALE meta-analysis of activation patterns in phantom limb pain: Novel insights into multisensory integration across movement tasks, facial stimulation, and pain-reducing interventions

Background

Phantom limb pain (PLP) is a debilitating neuropathic pain syndrome characterized by the perception of pain in an amputated or deafferented limb. Maladaptive cortical reorganization is proposed as its primary mechanism, yet a comprehensive analysis of functional alterations is lacking due to methodological variability across studies.

Methods

We employed an activation likelihood estimation (ALE) meta-analysis of fMRI and [¹⁵O]H₂O-PET studies to compare brain activity in post-amputation PLP patients with that of healthy controls. A systematic search of PubMed, Embase, Scopus, Cochrane Library, and Web of Science identified relevant studies. Following exclusion of unsuitable studies, an ALE meta-analysis was conducted with sub-analyses for movement tasks, facial stimulation, and pain-reducing interventions.

Results

A total of 972 articles was identified, of which eleven met the inclusion criteria. ALE results of the sub-analysis for facial stimulation (four studies; 43 PLP patients) showed increased activation in medial pain network regions (e.g., anterior cingulate cortex and anterior insula). The movement analysis sub-analysis (seven studies, 66 PLP patients) revealed heightened activity in the same medial pain network regions, though also in multisensory integration areas, particularly the posterior parietal cortex (PPC). Intervention-related analyses (four studies, 46 PLP patients) demonstrated reduced activation in the PPC but not in the medial pain network regions.

Conclusion

The observed hyperactivity in multisensory integration regions supports the hypothesis that PLP arises from attempts to reconcile conflicting sensory inputs, leading to a dysregulated PPC that modulates pain intensity. Further research should elucidate the role of the PPC in PLP, guiding novel therapeutic interventions.