The American Society of Pain and Neuroscience (ASPN) Guidelines and Consensus on the Definition, Current Evidence, Clinical Use and Future Applications for Physiologic Closed-Loop Controlled Neuromodulation in Chronic Pain: A NEURON Group Project

Author: Jason E Pope1, Timothy Ray Deer2, Dawood Sayed3, Ajay B Antony4, Harjot Singh Bhandal1, Aaron K Calodney5, Krishnan Chakravarthy6, Shrif Costandi7, Jack Diep8, Shravani Durbhakula9, Michael A Fishman10, Christopher Gilligan11, Johnathan Heck Goree12, Maged Guirguis13, Jonathan Michael Hagedorn14, Corey William Hunter15,16, Jan Willem Kallewaard17,18, Leonardo Kapural19,20,21, Christopher M Lam3, Sean Li22, Brian Mayrsohn23,24, Harold Nijhuis25, Serge Nikolic26, Erika A Petersen27, Lawrence Raymond Poree28, Shawn K Puri29, David E Reece30, Steven Mark Rosen31, Marc A Russo32, Jay M Shah33, Peter Sean Staats34, Paul Verrills35, Chau M Vu1, Robert M Levy36, Nagy Mekhail37
Affiliation:
1 Evolve Restorative Center, Santa Rosa, CA, USA.
2 Pain Services, The Spine & Nerve Center of the Virginias, Charleston, WV, USA.
3 Department of Anesthesiology and Pain Medicine, The University of Kansas Medical Center, Kansas City, KS, USA.
4 The Orthopaedic Institute, Gainesville, FL, USA.
5 Clinical Research, Precision Spine Care, Tyler, TX, USA.
6 Anesthesiology and Pain Medicine, Solaris Research Institute, Wilmington, DE, USA.
7 Pain Medicine, Cleveland Clinic, Cleveland, OH, USA.
8 Nevada Pain Management, Las Vegas, NV, USA.
9 Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN, USA.
10 Michael Fishman MD PLLC, Lebanon, PA, USA.
11 Robert Wood Johnson University Hospital, New Brunswick, NJ, USA.
12 Department of Anesthesiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
13 Interventional Pain Management Department, Ochsner Health System, New Orleans, LA, USA.
14 Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA.
15 Ainsworth Institute of Pain Management, New York City, NY, USA.
16 Physical Medicine & Rehabilitation, Icahn School of Medicine at Mount Sinai Hospital, New York City, NY, USA.
17 Amsterdam University Medical Centre, Amsterdam, The Netherlands.
18 Rijnstate Hospital, Arnhem, The Netherlands.
19 Carolinas Pain Institute, Winston Salem, NC, USA.
20 Centers for Clinical Research, Winston Salem, NC, USA.
21 Chronic Pain Research Institute, Winston Salem, NC, USA.
22 National Spine and Pain Centers, Shrewsbury, NJ, USA.
23 Interventional Pain Management, Maywell Health, Plainview, NY, USA.
24 Interventional Pain Management, Maywell Health, New York City, NY, USA.
25 Anesthesiology, St Antonius Hospital, Nieuwegein, Utrecht, The Netherlands.
26 Pain Medicine and Neuromodulation, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.
27 Department of Neurosurgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
28 Anesthesia- Division of Pain Medicine, University of California, San Francisco, CA, USA.
29 Integrated Pain Associates, Killeen, TX, USA.
30 Absolute Pain Management, Rockville, MD, USA.
31 Delaware Valley Pain and Spine Institute, Trevose, PA, USA.
32 School of Biomedical Sciences, University of Newcastle, Newcastle, NSW, Australia.
33 Samwell Institute of Pain Management, Colonia, Livingston, and Englewood, NJ, USA.
34 National Spine and Pain Centers, Atlantic Beach, FL, USA.
35 Metropain, Melbourne, VIC, Australia.
36 Neuromodulation: Technology at the Neural Interface, International Neuromodulation Society, Boca Raton, FL, USA.
37 Evidence-Based Pain Management Research, Cleveland Clinic, Cleveland, OH, USA.
Conference/Journal: J Pain Res
Date published: 2025 Feb 3
Other: Volume ID: 18 , Pages: 531-551 , Special Notes: doi: 10.2147/JPR.S475527. , Word Count: 315


Introduction:
Neuromodulation has been a staple of treatment for moderate-to-severe chronic refractory pain since the introduction of the first spinal cord stimulator by Norman Shealy in 1967. Appreciating the dynamic nature of electrical modulation of the nervous system from the epidural space, the goal has been consistent, reliable, and therapeutic neural activation of the spinal cord. This has proven to be extremely difficult. Recently, the Food and Drug Administration (FDA) released a guidance on physiologic closed loop controlled (PCLC) devices, highlighting the potential for these therapies to deliver accurate, consistent, real-time therapy, enhancing medical care and reducing variability. Because of the growing neuromodulation market focus on PCLC strategies, the American Society of Pain and Neuroscience (ASPN) sought to develop guidance on safety and efficacy, along with a taxonomy surrounding PCLC systems (PCLCSs) and to develop an evidence-based best practice review.

Methods:
A librarian-assisted literature search was performed to identify manuscripts relevant to the topic of PCLC stimulation for management of chronic pain. Initial literature search was performed utilizing MEDLINE, EMBASE, Cochrane database, BioMed Central, and Web of Science. Included manuscripts encompassed meta-analyses, systematic reviews, randomized controlled trials (RCTs), prospective or retrospective studies with follow-up to 12 months, limited to the English language. MESH terms utilized included "closed-loop", "physiologic closed loop controlled", "spinal cord stimulation", "closed loop feedback", "feedback controlled", "neuromodulation", "pain", "persistent pain", "neuropathic pain", and "chronic pain". The modified USPSTF evidence and recommendation grading strategy previously utilized was again employed.

Results:
Four studies were identified for review, 2 prospective, one retrospective, and one randomized controlled study with at least 12-month follow-up.

Conclusion:
PCLC neuromodulation is an innovation that requires a responsible introduction. As commercial access grows, there is a responsibility that requires consistency with definition, evidence generation, focused on safety and efficacy.

Keywords: chronic pain; clinical evidence review; closed loop stimulation; neuromodulation; neuropathic pain; physiologic closed loop stimulation; spinal cord stimulation.

PMID: 39926188 PMCID: PMC11804234 DOI: 10.2147/JPR.S475527

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