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.