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

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. Low back pain is a major health problem in United States and worldwide. In many cases, it can become chronic. Low back pain can be caused by many disorders such as lumbar herniated discs and compression of nerve roots. The clinical use of epidural steroid

Mineralocorticoid Antagonist Improves Glucocorticoid Receptor Signaling and Dexamethasone Analgesia in an Animal Model of Low Back Pain

“…Low back pain is a major health issue and common cause of chronic pain. It is prevalent in one third of the US population (Johannes et al, 2010 ; Ibrahim et al, 2016 ). It is the most common cause of chronic pain.…”

“…Dexamethasone (DEX), a high potency, long acting glucocorticoid has been increasingly used as an epidural steroid injection for low back pain management, in part because it is viewed as a safer, non-particulate steroid (Schneider et al, 2015 ). Other steroids commonly used for epidural injections include betamethasone, 6-α-methylprednisolone and triamcinolone (Ibrahim et al, 2016 ). These clinically used steroids activate the glucocorticoid receptor (GR).…”

“…MR is expressed in cells other than kidney such as cardiomyocytes (Messaoudi and Jaisser, 2011 ), brain neurons (Joels et al, 2008 ) and dorsal root ganglia (DRG) neurons (Dong et al, 2012 ). In other tissues, MR activation is pro-inflammatory and implicated in organ damage such as in heart, kidney and vasculature (Ibrahim et al, 2016 ; Belden et al, 2017 ). The pro-inflammatory effects of MR activation can counteract the desired GR anti-inflammatory effects of the epidural steroid injection.…”

High‐dose spironolactone lacks effectiveness in treatment of fibromyalgia (RCT)

“…Thus, it is not surprising that SPL has been investigated for its therapeutic potential in various neuropsychiatric disorders such as depression (Hinkelmann et al., 2016; Juruena et al., 2013; de Kloet et al., 2016), schizophrenia (Hasan et al., 2020; Wehr et al., 2017) or processing of stress responses (Schwabe, Höffken, et al., 2013; Schwabe, Tegenthoff, et al., 2013; Vogel et al., 2015, 2017). Furthermore and relevant for this study, MR has been shown to be involved in pain pathophysiology and MR antagonists including SPL reduce nociception and pain (Dong et al, 2012; Ibrahim et al., 2016; Li et al., 2018; Lilius et al., 2014; Tafelski et al., 2019).…”