Regenerative Medicine: Pharmacological Considerations & Clinical Role in Pain Management

Learning Objectives

As a result of participating in this activity, learners will be able/better able to:

• Apply a greater understanding of neuroimmune interactions to address neuropathic pain
• Influence disease process through neuroimmune modulation
• Select patients who are likely to benefit from regenerative medicine procedures
  

Accreditation & Designation

Neurovations Education is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Neurovations Education designates this live activity for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

This activity includes discussions of unlabeled or investigational uses of commercial and/or developmental products.

This activity includes discussions and explorations of new and evolving topics. Such inclusion includes adequate justifications of statements based upon current science, evidence and clinical reasoning.

Disclosure of Financial Relationships

Neither the presenters, reviewers nor any other person with control of, or responsibility for, the planning, delivery, or evaluation of accredited continuing education has, or has had within the past 24 months, any financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

Desirable Physician Attributes

• Patient Care [ACGME/ABMS] Provide care that is compassionate, appropriate and effective for the treatment of health problems and the promotion of health
• Medical Knowledge [ACGME/ABMS] about established and evolving biomedical, clinical, and cognate (e.g. epidemiological and social-behavioral) sciences and the application of this knowledge to patient care
• Employ Evidenced-based Practice [IOM] Integrate best research with clinical expertise and patient values for optimum care, and participate in learning and research activities to the extent feasible
• Professionalism [ACGME/ABMS] Carrying out professional responsibilities, ethics, sensitivity
• Interpersonal and Communication Skills [ACGME/ABMS] Effective information exchange, teaming with patients and families

Pain management domains and core competencies

• 1. Multidimensional nature of pain: What is pain?
  • Describes how cultural, institutional, societal, and regulatory influences affect assessment and management of pain
  • Demonstrates knowledge of the theories and science for understanding the physiology of pain and
    pain transmission

• 2. Pain assessment and measurement: How is pain assessed and measured?
  • Demonstrates empathic, compassionate, and professional communication during pain assessment

• 3. Treatment: How is pain safely and effectively treated?
  • Identifies appropriate multimodal pain treatment options as part of a comprehensive pain management plan
  • Identifies and describes potential pharmacological and nonpharmacological treatment options
  • Develops a pain treatment plan based on benefits and risks of available treatments

Additional Reading

• Buchheit, T., Huh, Y., Maixner, W., Cheng, J., & Ji, R. R. (2020). Neuroimmune modulation of pain and regenerative pain medicine. The Journal of Clinical Investigation, 130(5), 2164-2176.
• Benzon, H. M., Rathmell, J. P., Wu, C. L., Turk, D. C., Argoff, C. E., & Hurley, R. W. (2022). Practical Management of Pain E-Book. Elsevier Health Sciences.
• Spees, J. L., Lee, R. H., & Gregory, C. A. (2016). Mechanisms of mesenchymal stem/stromal cell function. Stem cell research & therapy, 7(1), 1-13.
• Toh, W. S., Lai, R. C., Hui, J. H. P., & Lim, S. K. (2017, July). MSC exosome as a cell-free MSC therapy for cartilage regeneration: implications for osteoarthritis treatment. In Seminars in cell & developmental biology (Vol. 67, pp. 56-64). Academic Press.
• Najar, M., Krayem, M., Merimi, M., Burny, A., Meuleman, N., Bron, D., ... & Lagneaux, L. (2018). Insights into inflammatory priming of mesenchymal stromal cells: functional biological impacts. Inflammation Research, 67(6), 467-477.
• Pittenger, M. F., Discher, D. E., Péault, B. M., Phinney, D. G., Hare, J. M., & Caplan, A. I. (2019). Mesenchymal stem cell perspective: cell biology to clinical progress. NPJ Regenerative medicine, 4(1), 1-15.
• Chen, G., Park, C. K., Xie, R. G., & Ji, R. R. (2015). Intrathecal bone marrow stromal cells inhibit neuropathic pain via TGF-β secretion. The Journal of clinical investigation, 125(8), 3226-3240.
• Choi, B. Y., Song, J. J., Chang, S. O., Kim, S. U., & Oh, S. H. (2012). Intravenous administration of human mesenchymal stem cells after noise-or drug-induced hearing loss in rats. Acta oto-laryngologica, 132(sup1), S94-S102.
• Hua, Z., Liu, L., Shen, J., Cheng, K., Liu, A., Yang, J., ... & Cheng, J. (2016). Mesenchymal stem cells reversed morphine tolerance and opioid-induced hyperalgesia. Scientific reports, 6(1), 1-13.
• Olmedo-Moreno L, et al. Heterogeneity of In Vitro Expanded Mesenchymal Stromal Cells and Strategies to Improve Their Therapeutic Actions. Pharmaceutics. 2022 May 23;14(5):1112.
• Almeria C, Kreß S, Weber V, Egger D, Kasper C. Heterogeneity of mesenchymal stem cell-derived extracellular vesicles is highly impacted by the tissue/cell source and culture conditions. Cell Biosci. 2022 May 2;12(1):51.
• Levy, O., Kuai, R., Siren, E. M., Bhere, D., Milton, Y., Nissar, N., ... & Karp, J. M. (2020). Shattering barriers toward clinically meaningful MSC therapies. Science Advances, 6(30), eaba6884.
• Schneider, B. J., Hunt, C., Conger, A., Qu, W., Maus, T. P., Vorobeychik, Y., ... & McCormick, Z. L. (2021). The effectiveness of intradiscal biologic treatments for discogenic low back pain: a systematic review. The Spine Journal.
• Vij, R., Stebbings, K. A., Kim, H., Park, H., & Chang, D. (2022). Safety and efficacy of autologous, adipose-derived mesenchymal stem cells in patients with rheumatoid arthritis: a phase I/IIa, open-label, non-randomized pilot trial. Stem Cell Research & Therapy, 13(1), 1-9.
• Lopez-Santalla, M., Fernandez-Perez, R., & Garin, M. I. (2020). Mesenchymal stem/stromal cells for rheumatoid arthritis treatment: an update on clinical applications. Cells, 9(8), 1852.
• Matas, J., Orrego, M., Amenabar, D., Infante, C., Tapia-Limonchi, R., Cadiz, M. I., ... & Espinoza, F. (2019). Umbilical cord-derived mesenchymal stromal cells (MSCs) for knee osteoarthritis: repeated MSC dosing is superior to a single MSC dose and to hyaluronic acid in a controlled randomized phase I/II trial. Stem cells translational medicine, 8(3), 215-224.
• Ma, W., Liu, C., Wang, S., Xu, H., Sun, H., & Fan, X. (2020). Efficacy and safety of intra-articular injection of mesenchymal stem cells in the treatment of knee osteoarthritis: A systematic review and meta-analysis. Medicine, 99(49).
• Song Y, Zhang J, Xu H, Lin Z, Chang H, Liu W, Kong L. Mesenchymal stem cells in knee osteoarthritis treatment: A systematic review and meta-analysis. J Orthop Translat. 2020;24:121-130.