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Review
. 2024 Sep 11:17:2951-3001.
doi: 10.2147/JPR.S480559. eCollection 2024.

Evidence-Based Clinical Practice Guidelines on Regenerative Medicine Treatment for Chronic Pain: A Consensus Report from a Multispecialty Working Group

Ryan S D'Souza  1 , Yeng F Her  1 , Nasir Hussain  2 , Jay Karri  3 , Michael E Schatman  4 , Aaron K Calodney  5 , Christopher Lam  6 , Thomas Buchheit  7 , Brennan J Boettcher  8 , George C Chang Chien  9 , Scott G Pritzlaff  10 , Christopher Centeno  11 , Shane A Shapiro  12 , Johana Klasova  1 , Jay S Grider  13 , Ryan Hubbard  14 , Eliana Ege  15 , Shelby Johnson  8 , Max H Epstein  16 , Eva Kubrova  8 , Mohamed Ehab Ramadan  17 , Alexandra Michelle Moreira  18 , Swarnima Vardhan  19 , Yashar Eshraghi  20 , Saba Javed  21 , Newaj M Abdullah  22 , Paul J Christo  17 , Sudhir Diwan  23 , Leslie C Hassett  24 , Dawood Sayed  6 , Timothy R Deer  25
Affiliations
Review

Evidence-Based Clinical Practice Guidelines on Regenerative Medicine Treatment for Chronic Pain: A Consensus Report from a Multispecialty Working Group

Ryan S D'Souza et al. J Pain Res. .

Abstract

Purpose: Injectable biologics have not only been described and developed to treat dermal wounds, cardiovascular disease, and cancer, but have also been reported to treat chronic pain conditions. Despite emerging evidence supporting regenerative medicine therapy for pain, many aspects remain controversial.

Methods: The American Society of Pain and Neuroscience (ASPN) identified the educational need for an evidence-based guideline on regenerative medicine therapy for chronic pain. The executive board nominated experts spanning multiple specialties including anesthesiology, physical medicine and rehabilitation, and sports medicine based on expertise, publications, research, and clinical practice. A steering committee selected preliminary questions, which were reviewed and refined. Evidence was appraised using the United States Preventive Services Task Force (USPSTF) criteria for evidence level and degree of recommendation. Using a modified Delphi approach, consensus points were distributed to all collaborators and each collaborator voted on each point. If collaborators provided a decision of "disagree" or "abstain", they were invited to provide a rationale in a non-blinded fashion to the committee chair, who incorporated the respective comments and distributed revised versions to the committee until consensus was achieved.

Results: Sixteen questions were selected for guideline development. Questions that were addressed included type of injectable biologics and mechanism, evidence in treating chronic pain indications (eg, tendinopathy, muscular pathology, osteoarthritis, intervertebral disc disease, neuropathic pain), role in surgical augmentation, dosing, comparative efficacy between injectable biologics, peri-procedural practices to optimize therapeutic response and quality of injectate, federal regulations, and complications with mitigating strategies.

Conclusion: In well-selected individuals with certain chronic pain indications, use of injectable biologics may provide superior analgesia, functionality, and/or quality of life compared to conventional medical management or placebo. Future high-quality randomized clinical trials are warranted with implementation of minimum reporting standards, standardization of preparation protocols, investigation of dose-response associations, and comparative analysis between different injectable biologics.

Keywords: bone marrow aspirate concentrate; injectable biologics; mesenchymal stem cell; pain medicine; platelet-rich plasma; regenerative medicine.

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Conflict of interest statement

RSD received investigator-initiated research grant funding from Nevro Corp and Saol Therapeutics paid to his institution. MES is a research consultant for Apurano, outside the submitted work. AKC is a consultant for Medtronic, Companion Spine, PainTeq, and Vertos; a speaker for Relievant; and receives research support from Medtronic, Nevro Corp, Stryker, Boston Scientific, Spine Biopharma, Biorestorative, Vivex, Vertos, DiscGenics, ReGelTec, Saol Therapeutics, PainTeq, Saluda, and Relievant. SGP is a consultant for Bioness, SPR Therapeutics, Nalu Medical, Medtronic; receives royalties from Oxford University Press and Wolters Kluwer; and receives research grant funding from Medtronic, Nevro Corp, Abbott, and Biotronik. CC is a shareholder and patent holder and chief medical officer of Regenexx LLC. SAS is on the board of directors for The Biologic Association (non-profit). YE is a research consultant for Autonomous Healthcare Inc, is on the advisory board for Saluda Medical Americas Inc and SPR Therapeutics. DS is a consultant to Abbott, Painteq, Saluda, Mainstay, Surgentec, Nevro, and holds stock options with Painteq, Neuralace, Mainstay, Vertos, and SPR Therapeutics. SD serves on the advisory board for CornerLoc. TRD is a consultant for Abbott, Vertos, SpineThera, Saluda Medical, Cornerloc, SPR Therapeutics, PainTeq, Spinal Simplicity, Aurora and Biotronik; he is an advisory board member for Abbott, Vertos, SPR Therapeutics, and Biotronik; he has a DRG Lead patent that is pending with Abbott; he has funded research with Abbott, Vertos, Saluda, Mainstay, SPR Therapeutic, Boston Scientific, and PainTeq. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Diagram displaying adult and perinatal sources of mesenchymal stem cells. Adapted with permission from Hoang DM et al. Stem cell-based therapy for human diseases. Signal Transduct Target Ther. 2022 Aug 6;7(1):272.
Figure 2
Figure 2
Diagram displaying bone marrow aspiration technique. Two approaches to bone marrow aspiration are displayed in this figure. We advise the approach from the posterior superior iliac spine to the anterior inferior iliac spine (novel approach) due to its safety margin away from the greater sciatic notch. Adapted with permission from D’Souza et al. A three-dimensional computed tomography study to determine the ideal method for fluoroscopically guided bone marrow aspiration from the iliac crest. Bosn J Basic Med Sci. 2021 Jun 1;21(3):370–377.
Figure 3
Figure 3
Diagram displaying bone marrow aspiration. Fluoroscopic imaging of the posterior iliac crest with the Jamshidi needle. A hammer is used to gently penetrate the cortex of the iliac crest prior to aspiration.
Figure 4
Figure 4
Processing of bone marrow aspirate to create bone marrow aspirate concentrate. Note the three fractions of the bone marrow aspirate after centrifugation. The fraction of interest is in the middle buffy coat directly above the dark red blood cells.
See this image and copyright information in PMC

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