Neuromodulation to prevent the chronification of phantom limb pain: A theoretical neural circuit model

J Pain. 2026 Jul;44:106309. doi: 10.1016/j.jpain.2026.106309. Epub 2026 May 5.

ABSTRACT

The central mechanisms of chronic phantom limb pain (PLP) are widely investigated, yet those underlying the transition from acute to chronic PLP (PLP chronification) are overlooked. Using insights from neuroscience of phantoms and pain phenomena, we propose a new, theoretical neural circuit model for PLP and its chronification. In this focus article, we suggest that maladaptive connectivity within and between specific neural circuits (multisensory integration, salience, and prefrontal modulatory) underlies PLP and its chronification. This conceptual theoretical model is supported by findings that a combination of neuromodulatory techniques (mirror therapy and transcranial direct current stimulation) prevented PLP chronification. Current literature suggests that mirror therapy modulates the multisensory integration circuit and that transcranial motor cortex stimulation may modulate the salience and prefrontal modulatory neural circuits. According to our proposed conceptual theoretical model, the combined therapy applied at the acute stage of PLP might prevent chronic PLP, suggesting the importance of these neural circuits in PLP chronification and its persistence. This framework aims to generate testable hypotheses, and its validity depends on future empirical studies. PERSPECTIVE: This paper offers a perspective on phantom limb pain (PLP), highlighting the often-overlooked shift from acute to chronic PLP. It introduces a theoretical neural circuit model connecting multisensory, salience, and prefrontal circuits, while emphasizing early combined neuromodulation as a promising approach to preventing PLP from becoming chronic.

PMID:42097471 | DOI:10.1016/j.jpain.2026.106309