The Stochastic Entanglement and Phantom Motor Execution Hypotheses: A Theoretical Framework for the Origin and Treatment of Phantom Limb Pain

Phantom limb pain (PLP) is a debilitating condition common after amputation that can considerably hinder patients' quality of life. Several treatments have reported promising results in alleviating PLP. However, clinical evaluations are usually performed in small cohorts and rigorous clinical trials are scarce. In addition, the underlying mechanisms by which novel interventions alleviate PLP are often unclear, potentially because the condition itself is poorly understood. This article presents a theoretical framework of PLP that can be used as groundwork for hypotheses of novel treatments. Current hypotheses on the origins of PLP are discussed in relation to available clinical findings. Stochastic entanglement of the pain neurosignature, or connectome, with impaired sensorimotor circuitry is proposed as an alternative hypothesis for the genesis of PLP, and the implications and predictions this hypothesis entails are examined. In addition, I present a hypothesis for the working mechanism of Phantom Motor Execution (PME) as a treatment of PLP, along with its relation to the aforementioned stochastic entanglement hypothesis, which deals with PLP's incipience. PME aims to reactivate the original central and peripheral circuitry involved in motor control of the missing limb, along with increasing dexterity of stump muscles. The PME hypothesis entails that training of phantom movements induces gradual neural changes similar to those of perfecting a motor skill, and these purposefully induced neural changes disentangle pain processing circuitry by competitive plasticity. This is a testable hypothesis that can be examined by brain imaging and behavioral studies on subjects undergoing PME treatment. The proposed stochastic entanglement hypothesis of PLP can be generalized to neuropathic pain due to sensorimotor impairment, and can be used to design suitable therapeutic treatments.