Jordan Sam1, Michael Catapano2, Sachin Sahni3, Frederick Ma4, Alaa Abd-Elsayed5, Ognjen Visnjevac6. 1. Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada. 2. Dept. of Physical Medicine and Rehabilitation, University of Toronto, Toronto Rehabilitation Institute, Toronto, ON, Canada. 3. Dept. of Anesthesiology, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada. 4. Bloor Pain Specialists, Toronto, ON, Canada. 5. Department of Anesthesiology University of Wisconsin, School of Medicine and Public Health, Madison, WI. 6. Dept. of Anesthesiology, McMaster University Health, Hamilton, ON, Canada; Spine Pain Program, Bloor Pain Specialists, Toronto, ON, Canada; Cleveland Clinic Canada, Toronto, ON, Canada.
Abstract
BACKGROUND: Pulsed radiofrequency (PRF) treatment uses low energy, short pulsations to modulate tissue characteristics. PRF treatment has been effective as an interventional pain management technique to treat a variety of chronic neuropathic pain (neuralgia) disorders, but a comprehensive review of its biological mechanism has not been updated in a decade. OBJECTIVES: In this literature review, we performed a literature search in PubMed to identify publications describing the mechanisms of action of pulsed radiofrequency for pain indications. STUDY DESIGN: Narrative literature review. METHODS: A systematic search was performed through PubMed from database inception to December 31, 2019, to identify all articles addressing the cellular or molecular mechanisms of action of PRF on neuropathic pain. The search terms "pulsed radiofrequency" and "pulsed radiofrequency mechanisms" were used. Cellular and molecular mechanisms of PRF interventions were subdivided into 3 broad categories: nociceptive signalling, immune activity, and synaptic function. A total of 20 publications were identified for inclusion in this updated review. RESULTS: It was found that pulsed radiofrequency impacts many different biological pathways involved in the modulation of chronic neuropathic pain (neuralgia). With regards to nociceptive signalling, PRF treatment modulates ion channels (Na/K ATPase, HCN, P2X3), CGRP, neurotransmitters (aspartate, citrulline, M-ENK, glutamate), postsynaptic receptors (AMPA-R, GABA-B), and synaptic function (KCC2). PRF treatment also modulates immune activity, including microglial markers (CD3, CD56, Iba1), inflammatory cytokines (IL-6, IL-17, IRF8, IFN-g, TNFa), and intracellular proteins implicated in immune mediated neuropathic pain (BDNF, b-catenin, JNK, p38, ERK1/2). LIMITATIONS: This review is primarily limited by the diverse data sets that needed to be collated and correlated, as no study was comprehensive in addressing all markers, cytokines, pathways, neurotransmitters, ion channels, proteins, genes, and gene expression changes, along with their clinical outcomes concurrently. As such, the interplay of these individual pathways and mechanisms and their isolated effects on efficacy of PRF cannot be concluded. Rather, the large majority of findings can be seen as associations instead of definitive causal relationships to clinical outcomes. CONCLUSIONS: Herein describes a clinically relevant collated update describing the cellular and molecular mechanisms of action of PRF for pain management.
BACKGROUND: Pulsed radiofrequency (PRF) treatment uses low energy, short pulsations to modulate tissue characteristics. PRF treatment has been effective as an interventional pain management technique to treat a variety of chronic neuropathic pain (neuralgia) disorders, but a comprehensive review of its biological mechanism has not been updated in a decade. OBJECTIVES: In this literature review, we performed a literature search in PubMed to identify publications describing the mechanisms of action of pulsed radiofrequency for pain indications. STUDY DESIGN: Narrative literature review. METHODS: A systematic search was performed through PubMed from database inception to December 31, 2019, to identify all articles addressing the cellular or molecular mechanisms of action of PRF on neuropathic pain. The search terms "pulsed radiofrequency" and "pulsed radiofrequency mechanisms" were used. Cellular and molecular mechanisms of PRF interventions were subdivided into 3 broad categories: nociceptive signalling, immune activity, and synaptic function. A total of 20 publications were identified for inclusion in this updated review. RESULTS: It was found that pulsed radiofrequency impacts many different biological pathways involved in the modulation of chronic neuropathic pain (neuralgia). With regards to nociceptive signalling, PRF treatment modulates ion channels (Na/K ATPase, HCN, P2X3), CGRP, neurotransmitters (aspartate, citrulline, M-ENK, glutamate), postsynaptic receptors (AMPA-R, GABA-B), and synaptic function (KCC2). PRF treatment also modulates immune activity, including microglial markers (CD3, CD56, Iba1), inflammatory cytokines (IL-6, IL-17, IRF8, IFN-g, TNFa), and intracellular proteins implicated in immune mediated neuropathic pain (BDNF, b-catenin, JNK, p38, ERK1/2). LIMITATIONS: This review is primarily limited by the diverse data sets that needed to be collated and correlated, as no study was comprehensive in addressing all markers, cytokines, pathways, neurotransmitters, ion channels, proteins, genes, and gene expression changes, along with their clinical outcomes concurrently. As such, the interplay of these individual pathways and mechanisms and their isolated effects on efficacy of PRF cannot be concluded. Rather, the large majority of findings can be seen as associations instead of definitive causal relationships to clinical outcomes. CONCLUSIONS: Herein describes a clinically relevant collated update describing the cellular and molecular mechanisms of action of PRF for pain management.
Authors: Daniel de Moraes Ferreira Jorge; Stephany Cares Huber; Bruno Lima Rodrigues; Lucas Furtado Da Fonseca; Gabriel Ohana Marques Azzini; Carlos Amilcar Parada; Christian Paulus-Romero; José Fábio Santos Duarte Lana Journal: Int J Mol Sci Date: 2022-10-03 Impact factor: 6.208