Blocking the mineralocorticoid receptor improves effectiveness of steroid treatment for low back pain in rats.
BACKGROUND
Localized inflammation of lumbar dorsal root ganglia (DRG) may contribute to low back pain. Local injections of corticosteroids used for low back pain are sometimes ineffective. Many corticosteroids activate not only the target glucocorticoid receptor (GR) but also the mineralocorticoid receptor (MR), which may have proinflammatory effects countering the effects of GR activation.


METHODS
A low back pain model was implemented in rats (n = 6 to 10 per group) by locally inflaming the L5 DRG. Sensory neuron excitability and mechanical hypersensitivity of the hind paws were measured. Tested steroids were applied locally to the inflamed DRG or orally.


RESULTS
The selective MR blocker eplerenone reduced pain behaviors when given orally starting at the time of surgery, or starting 7 days later. The highly GR-selective agonist fluticasone, applied locally to the inflamed DRG, was much more effective in reducing mechanical hypersensitivity. The MR/GR agonist 6-α methylprednisolone, commonly injected for low back pain, reduced mechanical hypersensitivity when applied locally to the DRG but was less effective than fluticasone. Its effectiveness was improved by combining it with local eplerenone. All tested steroids reduced hyperexcitability of myelinated sensory neurons (n = 71 to 220 cells per group) after inflammation, particularly abnormal spontaneous activity.


CONCLUSIONS
This preclinical study indicates the MR may play an important role in low back pain involving inflammation. Some MR effects may occur at the level of the sensory neuron. It may be useful to consider the action of clinically used steroids at the MR as well as at the GR.
From the Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, Ohio. Current address: Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China (L.Y.).
Ling
L
Ye
Wenrui
W
Xie
Judith A
JA
Strong
Jun-Ming
JM
Zhang
D000730:Androstadienes / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D000077545:Eplerenone; D000068298:Fluticasone; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D007249:Inflammation / Q000150:complications; D017116:Low Back Pain / Q000188:drug therapy* / Q000209:etiology; D008775:Methylprednisolone / Q000627:therapeutic use; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D013148:Spironolactone / Q000031:analogs & derivatives / Q000627:therapeutic use
D000730:Androstadienes; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D000077545:Eplerenone; D000068298:Fluticasone; D008775:Methylprednisolone