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

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 Hunter^{15

16}, Jan Willem Kallewaard^{17

18}, Leonardo Kapural^{19

20

21}, Christopher M Lam³, Sean Li²², Brian Mayrsohn^{23

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

Affiliations

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.

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

Review

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

Jason E Pope et al. J Pain Res. 2025.

. 2025 Feb 3:18:531-551.

doi: 10.2147/JPR.S475527. eCollection 2025.

Authors

Affiliations

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.

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

Abstract

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.

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Conflict of interest statement

JEP is a consultant for Abbott, Medtronic, Saluda, Flowonix, SpineThera, PainTEQ, Vertos, Vertiflex, SPR Therapeutics, Tersera, Aurora, Spark, Ethos, Flowonix, Biotronik, Mainstay, WISE, Boston Scientific, Thermaquil, Stimgenics, and SpineThera; has received grant/research support from Abbott, Flowonix, Saluda, Aurora, PainTEQ, Ethos, Muse, Boston Scientific, SPR Therapeutics, Mainstay, Vertos, AIS, and Thermaquil; and is a shareholder for Vertos, SPR Therapeutics, PainTEQ, Aurora, Spark, Celeri Health, Neural Integrative Solutions, Pacific Research Institute, Thermaquil, Saluda, Abbott, SpineThera, and Axonics. TRD is a consultant for Abbott, Nervonik, Vertos, SpineThera, Saluda Medical, Cornerloc, SPR Therapeutics, PainTEQ, Spinal Simplicity, Aurora and Biotronik; an advisory board member for Abbott, Vertos, SPR Therapeutics, and Biotronik, has a DRG Lead patent that is pending with Abbott, and has funded research with Abbott, Vertos, Saluda, Mainstay, SPR Therapeutic, Boston Scientific, and PainTEQ. DS is a consultant to Abbott, PainTEQ, Saluda, Mainstay, Surgentec, Nevro, and holds stock options with PainTEQ, Neuralace, Mainstay, Vertos, and SPR. ABA is a consultant to Abbott, Boston Scientific, Saluda, Vertos, and PainTEQ, and has funded research with Abbott, Boston Scientific, Saluda, Nalu, PainTEQ, and Viadisc. HSB is a consultant for Saluda and Abbott. AKC is a consultant for Medtronic, Companion Spine, PainTEQ, and Vertos; a speaker for Relievant; and has received research support from Medtronic, Nevro, Stryker, Boston Scientific, Spine Biopharma, Biorestorative, Vivex, Vertos, DiscGenics, ReGelTec, Saol, PainTEQ, Saluda, and Relievant. KC is a consultant for Medtronic. SC has received research support from Saluda. JD is a consultant and on the medical advisory board for Boston Scientific. SD has no ongoing financial relationships, but has received former consulting payments from Averitas Pharma and Biotronik. MAF serves on advisory boards for Medtronic, Biotronik, Bridge Therapeutics, Wavegate, Wise Neuro, Biowave, and Thermaquil; has received clinical research funding from Medtronic and Biotronik; is faculty for Medtronic; is a speaker for Mainstay Medical and Collegium Pharmaceuticals; holds stock in Aurora Spine; is co-founder of Celeri Health; holds equity in Celeri Health Brixton Biosciences, and Thermaquil; and is employee and Chief Medical Officer of Brixton Biosciences. CG is a consultant for Saluda, Mainstay, Persica and Iliad Lifesciences; and has equity in Mainstay; on Board of Directors for International Neuromodulation Society; Editor in Chief for Pain Practice. JHG is a consultant for Abbott, Saluda Medical, and Stratus Medical; and has received research funding from SPR Therapeutics and Mainstay Medical. MG is a consultant for Saluda Medical, Boston Scientific, Avon Medical, Averitas Pharmaceutical, PainTEQ, Pacira Medical and Vivex Biologics. CH reports personal fees from Abbott, Saluda, Biotronik; stock options from Maintay and Nalu, outside the submitted work. JWK serves on advisory boards for Saluda, Medtronic and Boston Scientific. LK serves on advisory boards for Avanos, Neuralace, Neuros, PainTEQ, Presidio, and Biotronik; has received research funding from Nevro, Medtronic, Biotronik, Gimer, SAOL Therapeutics, Sollis, Man and Science, FUS, Saluda, Neuralace, Neuros, and Xalud; is a speaker for Nevro, Avanos, and Saluda; and holds stock options in Gamma Core. SL is a consultant for Avanos, Abbott, Averitas Pharmaceuticals, Biotronik, Nalu, NeuroOne, Nevro (ended), PainTEQ, Presidio, Saluda, SPR Therapeutics, and Vertos; has received research funding from Avanos, Averitas Pharmaceuticals, Biotronik, Ethos Laboratories (ended), Nalu, Neuralace, Nevro, PainTEQ, Saluda, and SPR Therapeutics; and holds equity in Nalu Medical and NeuroOne. HN is a consultant for Abbott and Saluda. SN is a consultant for Saluda, Nevro, and Stratus Medical. EAP has received research support from Mainstay, Medtronic, Nalu, Neuros Medical, Nevro Corp, ReNeuron, SPR, Surgical Information Systems, and Saluda, as well as personal fees from Abbott Neuromodulation, Biotronik, Medtronic Neuromodulation, Nalu, Neuros Medical, Nevro, Presidio Medical, Saluda, and Vertos; and holds stock options from SynerFuse and neuro42. LRP is a consultant for Medtronic and Saluda and holds stock options in Saluda and Nalu. SKP is a consultant for Abbott and received grant funding from Abbott. DER has no financial interest in any vendor and is a faculty educator for Saluda, Abbott, SPR Therapeutics, and Nevro. MAR holds stock options in Saluda and Presidio Medical and has minor equity holding in SPR Therapeutics. PSS has received research funding from Saluda and Nalu, is co-founder of electroCore, and is a research advisor for SPR, Biotronik, Nalu, and AIS Healthcare; in addition, Dr Peter Staats has a patent for High Dose Capsaicin with royalties paid to Averitas, and a patent for vagus nerve stimulation licensed to electroCore. PV is a consultant to for Saluda and Presidio and has received research funding from Saluda, Presidio, and Biotronik. CMV is a consultant for Saluda Medical and PainTEQ. RML is an unpaid consultant for Abbott, Biotronik, Nalu, and Saluda and holds stock options with Nalu and Saluda. NM functioned as the independent Medical Monitor of Saluda’s EVOKE study. JMH, CWH, CML, BM, SMR, and JMS report no competing interests.

Figures

**Figure 1**
Phases of an ECAP‐based spinal cord stimulation physiologic closed‐loop control system.

See this image and copyright information in PMC

References

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1. House WF, Urban J. Long term results of electrode implantation and electronic stimulation of the cochlea in man. Ann Otol Rhinol Laryngol. 1973;82(4):504–517. doi:10.1177/000348947308200408 - DOI - PubMed

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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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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