# Steroids and Steroid Receptors in Low Back Pain

> **NIH NIH R01** · UNIVERSITY OF CINCINNATI · 2020 · $347,600

## Abstract

Low back pain is a common ailment which can be debilitating and which becomes chronic in 30% of cases.
Many patients fail to achieve adequate relief for such chronic pain conditions with current therapies.
Inflammation of the lumbar dorsal root ganglia (DRG), e.g. secondary to an immune response to a ruptured
disc, may contribute to some forms of low back pain. Because inflammation plays an important role in back
pain, a common treatment involves local injections of anti-inflammatory corticosteroids. However, this
treatment has been controversial. Randomized clinical trials of these treatments have had mixed results, and
not all patients obtain relief from steroids. The nominal target of corticosteroid drugs is the glucocorticoid
receptor (GR). However, recent in vitro studies show that many steroids clinically used for back pain injections
(including 6-α methylprednisolone and triamcinolone) can also activate the mineralocorticoid receptor (MR)
with similar potency. The MR is best known as the target of aldosterone, promoting sodium reabsorption in the
kidney. However, this receptor is expressed in other cell types including cardiomyocytes, brain neurons, and
DRG neurons. In many tissues MR plays a pro-inflammatory role which would be expected to counteract the
anti-inflammatory effects of GR activation. Our hypothesis is that avoiding MR activation will increase the
efficacy of steroids used in treatment of low back pain. We will test this hypothesis with three specific aims
(SA), using two established preclinical models of low back pain. SA1. To further characterize effects of local
MR activation in contributing to back pain and molecular correlates of inflammation. We will determine the
effects of local mineralocorticoid blockade or activation, and MR receptor knockdown, in rat models of low back
pain, examining pain behaviors, sensory neuron excitability, cytokine profile, and histochemical measures of
inflammation and receptor activation. SA2. To test the hypothesis that clinically used glucocorticoids (GR
agonists) also activate the mineralocorticoid receptor, reducing their ability to improve back pain and molecular
correlates of inflammation. We will examine the effects of several steroids commonly used in low back pain
injections (all of which activate the MR in vitro), a highly glucocorticoid selective steroid used in in other clinical
settings, and the endogenous glucocorticoid corticosterone. SA3. To assess a novel therapeutic approach for
back pain by combining GR agonists with MR antagonists to improve back pain and molecular correlates of
inflammation. The steroids examined in SA2 will be tested in combination with mineralocorticoid antagonists or
knockdown. Our long term goal is to establish the preclinical basis for clinical trials testing our hypothesis that
mineralocorticoid antagonists may improve the response to locally injected steroids commonly used for low
back pain treatment. Such trials are made more feasible by the fac...

## Key facts

- **NIH application ID:** 9976979
- **Project number:** 5R01AR068989-05
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Jun-Ming Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $347,600
- **Award type:** 5
- **Project period:** 2016-07-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976979

## Citation

> US National Institutes of Health, RePORTER application 9976979, Steroids and Steroid Receptors in Low Back Pain (5R01AR068989-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9976979. Licensed CC0.

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