Pathophysiology of pain and mechanisms of neuromodulation: A narrative review (a neuron project)

Marcin Karcz, The Spine and Nerve Centers of the Virginias, Charleston, WV, USA.
Alaa Abd-Elsayed, Department of Anesthesiology, University of Wisconsin, Madison, WI, USA.
Krishnan Chakravarthy, Innovative Pain Treatment Solutions, San Diego, CA, USA.
Mansoor M. Aman, Aurora Pain Management, Aurora Health Care, Oshkosh, WI, USA.Follow
Natalie Strand, Anesthesiology and Perioperative Medicine, Mayo Clinic, Phoenix, AZ, USA.
Mark N. Malinowski, OhioHealth Neurological Physicians, OhioHealth Inc, Columbus, OH, USA.
Usman Latif, Department of Anesthesiology, University of Kansas Medical Center, Kansas City, KS, USA.
David Dickerson, Department of Pain Medicine, Northshore University Health System, Skokie, IL, USA.
Tolga Suvar, Department of Anesthesiology and Pain Medicine, Rush University Medical Center, Oak Park, IL, USA.
Timothy Lubenow, Department of Anesthesiology and Pain Medicine, Rush University Medical Center, Oak Park, IL, USA.
Evan Peskin, Department of Pain Management, Insight Institute of Neurosurgery & Neuroscience, Flint, MI, USA.
Ryan D'Souza, Anesthesiology and Perioperative Medicine, Mayo Clinic, Phoenix, AZ, USA.
Eric Cornidez, Pain Institute of Southern Arizona, Tucson, AZ, USA.
Andrew Dudas, Mays and Schnapp Neurospine and Pain, Memphis, TN, USA.
Christopher Lam, Department of Anesthesiology, University of Kansas Medical Center, Kansas City, KS, USA.
Michael Farrell Ii, Department of Pain Management, Erie County Medical Center, Buffalo, NY, USA.
Geum Yeon Sim, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Bayview Medical Center, Baltimore, MD, USA.
Mohamad Sebai, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rosa Garcia, Department of Physical Medicine & Rehabilitation, Larkin Hospital Health System, Miami, FL, USA.
Lucas Bracero, The Spine and Nerve Centers of the Virginias, Charleston, WV, USA.
Yussr Ibrahim, Department of Pain Management at Northern Light Health - Eastern Maine Medical Center, Bangor, ME, USA.
Syed Jafar Mahmood, Department of Pain Medicine, University of California Davis Health System, Sacramento, CA, USA.
Marco Lawandy, Department of Physical Medicine & Rehabilitation, Montefiore Medical Center, Bronx, NY, USA.
Daniel Jimenez, Department of Physical Medicine & Rehabilitation, Michigan State University, Lansing, MI, USA.
Leili Shahgholi, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kamil Sochacki, Department of Anesthesiology and Perioperative Medicine, Rutgers Robert Wood Johnson, New Brunswick, NJ, USA.
Mohamed Ehab Ramadan, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Vinicius Tieppo Francio, Division of Pain Medicine, Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
Dawood Sayed, Department of Anesthesiology, University of Kansas Medical Center, Kansas City, KS, USA.
Timothy Deer, The Spine and Nerve Centers of the Virginias, Charleston, WV, USA.

Affiliations

Aurora Health Care, Oshkosh

Abstract

Pain serves as a vital innate defense mechanism that can significantly impact an individual's quality of life. Understanding the physiological effects of pain well plays an important role in developing novel pain treatments. Nociceptor neurons play a key role in pain and inflammation. Interactions between nociceptors and the immune system occur both at the site of injury and within the central nervous system. Modulating chemical mediators and nociceptor activity offers promising new approaches to pain management. Essentially, the sensory nervous system is essential for modulating the body's protective response, making it critical to understand these interactions to discover new pain treatment strategies. New innovations in neuromodulation have led to alternatives to opioids individuals with chronic pain with consequent improvement in disease-based treatment and nerve targeting. New neural targets from cellular and structural perspectives have revolutionized the field of neuromodulation. This narrative review aims to elucidate the mechanisms of pain transmission and processing, examine the characteristics and properties of nociceptors, and explore how the immune system influences pain perception. It further provides an updated overview of the physiology of pain and neuromodulatory mechanisms essential for managing acute and chronic pain. We assess the current understanding of different pain types, focusing on key molecules involved in each type and their physiological effects. Additionally, we compare painful and painless neuropathies and discuss the neuroimmune interactions involved in pain manifestation.

Document Type

Article

PubMed ID

39583192

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