1. Mineralocorticoid Receptor Antagonism Reduces Inflammatory Pain Measures in Mice Independent of the Receptors on Sensory Neurons.
- Author
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Qualls, Katherine A., Xie, Wenrui, Zhang, Jietong, Lückemeyer, Debora Denardin, Lackey, Sierra V., Strong, Judith A., and Zhang, Jun-Ming
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MINERALOCORTICOID receptors , *SENSORY receptors , *SENSORY neurons , *PAIN measurement , *DORSAL root ganglia , *LUMBAR pain - Abstract
• The mineralocorticoid receptor, expressed in DRG, may have a pro-inflammatory role. • Local MR blockade improves pain behaviors in a mouse radiculopathy model. • Sensory neuron specific MR knockout does not affect pain behaviors. • Unexpectedly, sensory neuron MR knockout increases nociceptor excitability. • These complexities may be relevant to understanding epidural steroid treatments. Corticosteroids are commonly used in the treatment of inflammatory low back pain, and their nominal target is the glucocorticoid receptor (GR) to relieve inflammation. They can also have similar potency at the mineralocorticoid receptor (MR). The MR has been shown to be widespread in rodent and human dorsal root ganglia (DRG) neurons and non-neuronal cells, and when MR antagonists are administered during a variety of inflammatory pain models in rats, pain measures are reduced. In this study we selectively knockout (KO) the MR in sensory neurons to determine the role of MR in sensory neurons of the mouse DRG in pain measures as MR antagonism during the local inflammation of the DRG (LID) pain model. We found that MR antagonism using eplerenone reduced evoked mechanical hypersensitivity during LID, but MR KO in paw-innervating sensory neurons only did not. This could be a result of differences between prolonged (MR KO) versus acute (drug) MR block or an indicator that non-neuronal cells in the DRG are driving the effect of MR antagonists. MR KO unmyelinated C neurons are more excitable under normal and inflamed conditions, while MR KO does not affect excitability of myelinated A cells. MR KO in sensory neurons causes a reduction in overall GR mRNA but is protective against reduction of the anti-inflammatory GRα isoform during LID. These effects of MR KO in sensory neurons expanded our understanding of MR's functional role in different neuronal subtypes (A and C neurons), and its interactions with the GR. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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