Peripherally Induced Reconditioning of the Central Nervous System: A Proposed Mechanistic Theory for Sustained Relief of Chronic Pain with Percutaneous Peripheral Nerve Stimulation

Timothy R Deer,¹ Sam Eldabe,² Steven M Falowski,³ Marc A Huntoon,⁴ Peter S Staats,⁵ Isaac R Cassar,⁶ Nathan D Crosby,⁶ Joseph W Boggs<sup>6

1</sup>The Spine and Nerve Center of the Virginias, Charleston, WV, USA; ²Department of Pain Medicine, The James Cook University Hospital, Middlesbrough, UK; ³Department of Neurosurgery, Neurosurgical Associates of Lancaster, Lancaster, PA, USA; ⁴Anesthesiology, Virginia Commonwealth University Medical Center, Richmond, VA, USA; ⁵Premier Pain Centers, Shrewsbury, NJ, USA; ⁶SPR Therapeutics, Cleveland, OH, USA

Correspondence: Timothy R Deer
The Spine and Nerve Center of the Virginias, 400 Court Street, Suite 100, Charleston, WV, 25301, USA
Tel +1 304/347-6141
Fax +1 304/347-6855
Email [email protected]

Abstract: Peripheral nerve stimulation (PNS) is an effective tool for the treatment of chronic pain, although its efficacy and utilization have previously been significantly limited by technology. In recent years, purpose-built percutaneous PNS devices have been developed to overcome the limitations of conventional permanently implanted neurostimulation devices. Recent clinical evidence suggests clinically significant and sustained reductions in pain can persist well beyond the PNS treatment period, outcomes that have not previously been observed with conventional permanently implanted neurostimulation devices. This narrative review summarizes mechanistic processes that contribute to chronic pain, and the potential mechanisms by which selective large diameter afferent fiber activation may reverse these changes to induce a prolonged reduction in pain. The interplay of these mechanisms, supported by data in chronic pain states that have been effectively treated with percutaneous PNS, will also be discussed in support of a new theory of pain management in neuromodulation: Peripherally Induced Reconditioning of the Central Nervous System (CNS).

Keywords: chronic pain, neuromodulation, peripheral nerve stimulation, cortical plasticity, peripherally induced reconditioning, mechanism of action