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      Mineralocorticoid Receptor, A Promising Target for Improving Management of Low Back Pain by Epidural Steroid Injections

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          Abstract

          Aim of review

          Low back pain is a major health problem in United States and worldwide. In this review, we aim to show that mineralocorticoid receptor (MR) activation has a critical role in the initiation of immune and inflammatory responses, which in turn can impact the effectiveness of the currently used steroids for epidural injections in low back pain management since most steroids activate MR in addition to the primary target, glucocorticoid receptor (GR). Moreover, we would like to determine some of the benefits of blocking the MR-induced negative effects. Overall, we propose a novel therapeutic approach for low back pain management by using a combination of a MR antagonist and a GR agonist in the epidural injections.

          Method

          We will first introduce the societal cost of low back pain and discuss how epidural steroid injections became a popular treatment for this condition. We will then describe several preclinical models used for the study of low back pain conditions and the findings with respect to the role of MR in the development of inflammatory low back pain.

          Recent findings

          MR has pro-inflammatory effects in many tissues which can counteract the anti-inflammatory effects induced by GR activation. Blocking MR using the selective MR antagonist eplerenone can reduce pain and sensory neuron excitability in experimental models of low back pain. Moreover, combining the MR antagonist with clinically used steroids is more effective in reducing pain behaviors than using the steroids alone.

          Summary

          MR antagonists are promising candidates to increase the effectiveness of currently used steroids. Since the activation of the MR is evident in preclinical models of low back pain, blocking its deleterious effects can be beneficial in managing inflammatory pain conditions.

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          Most cited references47

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          Classification of chronic pain. Descriptions of chronic pain syndromes and definitions of pain terms. Prepared by the International Association for the Study of Pain, Subcommittee on Taxonomy.

          (1986)
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            The coming out of the brain mineralocorticoid receptor.

            Corticosteroids - secreted after stress - have profound effects on brain and behavior. These effects are mediated by mineralocorticoid and glucocorticoid receptors, which are abundantly expressed in limbic neurons. The role of mineralocorticoid receptors in higher brain functions has never been well understood. Here we argue that the recently discovered low-affinity membrane version of the mineralocorticoid receptor contributes to the initial phase of the stress reaction; this is complemented by the glucocorticoid receptor which terminates the stress response. This concept may explain why human carriers of a mineralocorticoid receptor gene variant display enhanced neuroendocrine and autonomic responsiveness to a psychological stressor.
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              The IKK-NF-kappaB pathway: a source for novel molecular drug targets in pain therapy?

              Several studies indicate that the nuclear factor-kappa B (NF-kappaB) -activation cascade plays a crucial role not only in immune responses, inflammation, and apoptosis but also in the development and processing of pathological pain. Accordingly, a pharmacological intervention into this pathway may have antinociceptive effects and could provide novel treatment strategies for pain and inflammation. In this review we summarize the role of NF-kappaB in the nervous system, its impact on nociception, and several approaches that investigated the effects of various modulators of the classical I-kappaB-kinase-NF-kappaB signal transduction pathway in inflammatory nociception and neuropathic pain. The results indicate that NF-kappaB has an impact on nociceptive transmission and processing and that a number of substances that inhibit the NF-kappaB-activating cascade are capable of reducing the nociceptive response in different animal models. Therefore, a modulation of specific participants in the NF-kappaB signal transduction might exert a useful approach for the development of new painkillers.
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                Author and article information

                Journal
                101696487
                45921
                J Anesth Perioper Med
                J Anesth Perioper Med
                Journal of anesthesia and perioperative medicine
                2520-3002
                3 December 2016
                26 July 2016
                2016
                25 September 2017
                : 3
                : 4
                : 177-184
                Affiliations
                [1 ]Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, USA
                [2 ]Graduate Program in Molecular, Cellular, and Biochemical Pharmacology, University of Cincinnati, Cincinnati, USA
                Author notes
                Correspondence to Dr. Jun-Ming Zhang at jun-ming.zhang@ 123456uc.edu
                Article
                NIHMS831237
                10.24015/JAPM.2016.0023
                5611848
                549d05e5-a75a-4094-a434-96db01310f63

                This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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