Pulsed Radiofrequency in Interventional Pain Management: Cellular and Molecular Mechanisms of Action - An Update and Review.

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.

The duty to care in an influenza pandemic: a qualitative study of Canadian public perspectives.

Ever since the emergence of SARS, when we were reminded that the nature of health care practitioners' duty to care is greatly contested, it has remained a polarizing issue. Discussions on the nature and limits of health care practitioners' duty to care during disasters and public health emergencies abounds the literature, ripe with arguments seeking to ground its foundations. However, to date there has been little public engagement on this issue. This study involved three Townhall meetings held between February 2008 and May 2010 in three urban settings in Canada in order to probe lay citizens' views about ethical issues related to pandemic influenza, including issues surrounding the duty to care. Participants included Canadian residents aged 18 and over who were fluent in English. Data were collected through day-long facilitated group discussions using case scenarios and focus group guides. Participant's views were organized according to several themes, including the following main themes (and respective sub-themes): 1. Legitimate limits; a) competing obligations; and b) appeal to personal choice; and 2. Legitimate expectations; a) reciprocity; and b) enforcement and planning. Our findings show that participants moved away from categorical notions of the duty to care towards more equivocal and often normative views throughout deliberations. Our analysis contributes a better understanding of the constitutive nature of the duty to care, defined in part by taking account of public views. This broadened understanding can further inform the articulation of acceptable norms of duty to care and policy development efforts. What is more, it illustrates the urgent need for policy-makers and regulators to get clarity on obligations, responsibilities, and accountability in the execution of HCPs' duty to care during times of universal vulnerability.

Priority setting of ICU resources in an influenza pandemic: a qualitative study of the Canadian public's perspectives.

BACKGROUND: Pandemic influenza may exacerbate existing scarcity of life-saving medical resources. As a result, decision-makers may be faced with making tough choices about who will receive care and who will have to wait or go without. Although previous studies have explored ethical issues in priority setting from the perspective of clinicians and policymakers, there has been little investigation into how the public views priority setting during a pandemic influenza, in particular related to intensive care resources. METHODS: To bridge this gap, we conducted three public town hall meetings across Canada to explore Canadian's perspectives on this ethical challenge. Town hall discussions group discussions were digitally recorded, transcribed, and analyzed using thematic analysis. RESULTS: Six interrelated themes emerged from the town hall discussions related to: ethical and empirical starting points for deliberation; criteria for setting priorities; pre-crisis planning; in-crisis decision-making; the need for public deliberation and input; and participants' deliberative struggle with the ethical issues. CONCLUSIONS: Our findings underscore the importance of public consultation in pandemic planning for sustaining public trust in a public health emergency. Participants appreciated the empirical and ethical uncertainty of decision-making in an influenza pandemic and demonstrated nuanced ethical reasoning about priority setting of intensive care resources in an influenza pandemic. Policymakers may benefit from a better understanding the public's empirical and ethical 'starting points' in developing effective pandemic plans.

Restrictive measures in an influenza pandemic: a qualitative study of public perspectives.

OBJECTIVES: Recent experiences have demonstrated that restrictive measures remain a useful public health tool during infectious disease outbreaks. However, the use of restrictive measures is not without controversy, as there is no agreed-upon threshold for when and how to invoke restrictive measures. The objectives of this study are to solicit perspectives from Canadians on the ethical considerations of using restrictive measures in response to influenza pandemics, and in turn, to use public views to contribute to a better understanding of what is considered to be the justifiable use of restrictive measures. METHODS: A series of town hall focus groups with Canadian residents from June 2008 to May 2009, in three Canadian regions, in order to achieve broad public engagement (n=3 focus groups with a total of 17 participants). RESULTS: Two key themes emerged from all town hall focus groups: 1) create an environment for compliance through communication rather than enforcement, and 2) establish the delineation between individual rights, community values, and the greater good. CONCLUSION: While there is a need for a decision-making authority and even a mechanism for enforcement, our data suggest that a more tractable approach to restrictive measures is one that enables individuals to voluntarily comply by creating an environment to compel compliance based on communication. This approach requires restrictive measures to be a) proportional to the threat, b) implemented along with reciprocal arrangements provided to those affected, and c) accompanied by open and transparent communication throughout all stages so that citizens can both understand and participate in decision-making.

Contextualizing ethics: ventilators, H1N1 and marginalized populations.

If the H1N1 pandemic worsens, there may not be enough ventilated beds to care for all persons with respiratory failure. To date, researchers who explicitly discuss the ethics of intensive care unit admission and the allocation of ventilators during an influenza pandemic have based criteria predominantly on the principles of utility and efficiency, that is, promoting actions that maximize the greatest good for the greatest number of people. However, haphazardly applying utility and efficiency potentially disadvantages marginalized populations who might be at increased risk of severe reactions to H1N1. In Canada, Aboriginals represent 3% of Canadians, yet 11% of H1N1 cases requiring hospitalization involve Aboriginal persons. Aboriginal persons suffer from high rates of obesity due to socio-economic inequalities. Obesity is also a risk factor for severe H1N1 reactions. Yet, since obesity is found to increase the duration of stay in ventilated beds and a long stay is not considered an optimal use of ventilators, applying the principles of utility and efficiency may magnify existing social inequalities. Although promoting utility and efficiency is important, other ethical principles, such as equity and need, require thoughtful consideration and implementation. Furthermore, since public resources are being used to address a public health hazard, the viewpoints of the public, and specifically stakeholders who will be disproportionately affected, should inform decision-makers. Finally, giving attention to the needs and rights of marginalized populations means that ventilators should not be allocated based on criteria that exacerbate the social injustices faced by these groups of people.