Pathophysiology of Pain and Mechanisms of Neuromodulation: A Narrative Review (A Neuron Project)
Marcin Karcz, Alaa Abd‐Elsayed, Krishnan Chakravarthy, Mansoor Aman, Natalie Strand, Mark N. Malinowski, Usman Latif, David Dickerson, Tolga Suvar, Timothy R. Lubenow, Evan Peskin, Ryan S. D’Souza, Eric Cornidez, Andrew Dudas, Christopher Lam, Michael Farrell, Geum Yeon Sim, Mohamad E. Sebai, Rosa Garcia, Lucas Bracero, Yussr Ibrahim, S. Mahmood, Marco Lawandy, Daniel E. Jimenez, Leili Shahgholi, Kamil Sochacki, Mohamed Ehab Ramadan, Vinicius Tieppo Francio, Dawood Sayed, Timothy R. Deer
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.