Effect of intrathecal glucocorticoids on the central glucocorticoid receptor in a rat nerve ligation model

Rijsdijk, Mienke; Agalave, Nilesh M.; Wijck, Albert J. M. van; Kalkman, Cornelis J.; Ramachandran, Roshni; Baharpoor, Azar; Svensson, Camilla I.; Yaksh, Tony L.

doi:10.1016/j.sjpain.2016.12.008

Cited by 5 publications

(3 citation statements)

References 29 publications

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“…Strikingly, however, none of the contralateral knee joints showed significant synovitis post mortem , indicating that systemic reactivation induces some signs of inflammation (dolor, tumor) but not a full-blown synovitis. Another possibility is that the unilateral inflammation generated contralateral hypersensitivity due to plasticity of the central nervous system, including the spinal cord (Rijsdijk et al., 2017). However, pain symptoms are often observed before signs of inflammation are present in a joint developing RA, and increased pain sensitivity of non-inflamed sites has been observed in RA patients (Lee et al., 2009), while synovitis and pain do not always correlate (Forslind & Svensson, 2016).…”

Section: Discussionmentioning

confidence: 99%

Intra-articular injection of triamcinolone acetonide releasing biomaterial microspheres inhibits pain and inflammation in an acute arthritis model

et al. 2019

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Inflammation of the synovium and joint capsule is a main driver of pain in an osteoarthritic (OA) joint. Triamcinolone acetonide (TAA) is a classical corticosteroid that reduces synovitis and alleviates pain, albeit transiently. Biomaterial-based local TAA release may prolong the suppression of pain without the need for multiple injections. Polylactic-co-glycolic acid (PLGA) formulations of TAA prolong OA pain relief to a limited extent. A novel polyesteramide (PEA) microsphere platform allows for extended release in the OA joint for over 3 months. To evaluate their effect on pain and inflammation, TAA-loaded microspheres were intra-articularly delivered to the knee joint in a rat model of acute arthritis induced by intra-articular injection of streptococcal cell wall peptidoglycan-polysaccharide (PGPS) and subsequent flare-ups by intravenous PGPS injections. PEA-loaded microspheres were benchmarked with TAA-loaded PLGA microspheres and bolus TAA injection. TAA treatments were injected intra-articularly before the first induced flare-up. TAA-loaded PEA and PLGA microspheres reduced joint swelling and signs of pain-like behavior over the entire study period, as assessed by weight bearing and referred mechanical hypersensitivity, whereas bolus suspension was effective for a shorter time period. TAA-loaded PEA microspheres reduced lameness to a greater extent than TAA-loaded PLGA microspheres. In conclusion, a single intra-articular injection of TAA-loaded PEA microspheres reduced joint swelling and induced longer pain relief compared to bolus injection. Hence relief of inflammation and pain by PEA-based delivery of TAA may prove to be effective and durable.

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Section: Discussionmentioning

confidence: 99%

Intra-articular injection of triamcinolone acetonide releasing biomaterial microspheres inhibits pain and inflammation in an acute arthritis model

et al. 2019

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“…Our immunohistochemical experiments demonstrated that the GR was present most notably in neurons and also in some non-neuronal cells in the DRG, and was primarily observed in the nucleus with the antibody we used. Expression of the GR in the rodent DRG has been previously described (DeLeón et al, 1994 ; Lerch et al, 2017 ; Rijsdijk et al, 2017 ; Li et al, 2018 ), though there are some discrepancies between studies about the details of receptor distribution. GR expression in satellite glial cells has also been previously observed (Rijsdijk et al, 2017 ); as in our study, it appeared only a subset was GR-positive.…”

Section: Discussionmentioning

confidence: 99%

“…Expression of the GR in the rodent DRG has been previously described (DeLeón et al, 1994 ; Lerch et al, 2017 ; Rijsdijk et al, 2017 ; Li et al, 2018 ), though there are some discrepancies between studies about the details of receptor distribution. GR expression in satellite glial cells has also been previously observed (Rijsdijk et al, 2017 ); as in our study, it appeared only a subset was GR-positive. Our previous study showed that many DRG neurons also express the MR (Dong et al, 2012 ), and others have directly demonstrated co-localization of GR and MR within DRG neurons (Li et al, 2018 ), as well as within GR-rich regions of the brain such as hippocampus (Gomez-Sanchez and Gomez-Sanchez, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

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

Ibrahim

Xie

Strong

et al. 2018

Front. Cell. Neurosci.

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Low back pain, a leading cause of disability, is commonly treated by epidural steroid injections that target the anti-inflammatory glucocorticoid receptor (GR). However, their efficacy has been controversial. All currently used epidural steroids also activate the pro-inflammatory mineralocorticoid receptor (MR) with significant potency. Local inflammation of the dorsal root ganglia (DRG), a rat model of low back pain, was used. This model causes static and dynamic mechanical allodynia, cold allodynia and guarding behavior (a measure of spontaneous pain), and activates the MR, with pro-nociceptive effects. In this study, effects of local Dexamethasone (DEX; a glucocorticoid used in epidural injections), and eplerenone (EPL; a second generation, more selective MR antagonist) applied to the DRG at the time of inflammation were examined. Mechanical and spontaneous pain behaviors were more effectively reduced by the combination of DEX and EPL than by either alone. The combination of steroids was particularly more effective than DEX alone or the model alone (3-fold improvement for mechanical allodynia) at later times (day 14). Immunohistochemical analysis of the GR in the DRG showed that the receptor was expressed in neurons of all size classes, and in non-neuronal cells including satellite glia. The GR immunoreactivity was downregulated by DRG inflammation (48%) starting on day 1, consistent with the reduction of GR (57%) observed by Western blot, when compared to control animals. On day 14, the combination of DEX and EPL resulted in rescue of GR immunoreactivity that was not seen with DEX alone, and was more effective in reducing a marker for satellite glia activation/neuroinflammation. The results suggest that EPL may enhance the effectiveness of clinically used epidural steroid injections, in part by enhancing the availability of the GR. Thus, the glucocorticoid-mineralocorticoid interactions may limit the effectiveness of epidural steroids through the regulation of the GR in the DRG.

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Effects of Glucocorticoid Hormones on Pain Sensitivity: Involvement of Glucocorticoid and Mineralocorticoid Receptors

Yarushkina

Filaretova

2023

Neurosci Behav Physi

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Effect of intrathecal glucocorticoids on the central glucocorticoid receptor in a rat nerve ligation model

Abstract: Intrathecal MPA treatment after SNL did not result in lower tGR and pGR levels within the SDH and DRG compared to saline controls. In present study we did not differentiate between the various isoforms of the GR which might clarify this finding.

Cited by 5 publications

References 29 publications

Intra-articular injection of triamcinolone acetonide releasing biomaterial microspheres inhibits pain and inflammation in an acute arthritis model

Intra-articular injection of triamcinolone acetonide releasing biomaterial microspheres inhibits pain and inflammation in an acute arthritis model

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

Effects of Glucocorticoid Hormones on Pain Sensitivity: Involvement of Glucocorticoid and Mineralocorticoid Receptors

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