Systemic Inflammatory and Th17 Immune Activation among Patients Treated for Lumbar Radiculopathy Exceeds that of Patients Treated for Persistent Postoperative Neuropathic Pain

Shamji, Mohammed F.; Guha, Daipayan; Paul, Darcia; Shcharinsky, Alina

doi:10.1093/neuros/nyx052

Cited by 10 publications

(12 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accordingly, pain intensity was positively correlated with increased levels of Th17-cells and IL-17 expression. These research findings lead to the assumption that IL-17-producing T-helper cells trigger an inflammatory reaction and are responsible for the development and maintenance of pain [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the involvement of Th17-cells in the pathogenesis of canine spinal cord injury

et al. 2021

View full text Add to dashboard Cite

Intervertebral disc herniation (IVDH) is a frequently occurring neurological disease of dogs and the most common reason for spinal cord injury (SCI). Clinical signs are variable thus a reliable prognosis is crucial for further treatment decisions. Currently, the prognosis of IVDH primarily depends on presence or absence of deep pain perception. The purpose of this study was to investigate if Th17-cells could serve as a potential, prognostic biomarker for IVDH. We investigated a possible role of the adaptive immune system in the pathophysiology of IVDH in dogs. The investigation was performed by analyzing the influence of Th17-cells in blood and cerebrospinal fluid (CSF) of sixty-two dogs suffering from IVDH. In addition, we examined if Th17-cells might influence the course of this disease. As controls, paired blood and CSF samples of ten healthy clinic-owned dogs were examined and the values were compared to those of the IVDH group. Isolated lymphocytes were analyzed after stimulation by using multicolour flow cytometry to measure the number of Th17-cells. IL-17 levels were measured in paired serum and CSF samples by Enzyme‐linked Immunosorbent Assays (ELISA). Highly significant differences of stimulated Th17-cells in EDTA-blood samples could be determined between Th17-cell levels of dogs suffering from IVDH and the healthy control group and also between three sampling time points: preoperative, after clinical improvement and after six months. Preoperatively, Th17-cell levels were strongly decreased in contrast to the healthy controls. The decreased amount of Th17-cell levels recovered postoperatively so that Th17-cell levels of the last follow-up examinations were comparable to the control group after six months. At the same time IL-17 measured in serum preoperatively was significantly higher in dogs with IVDH than in healthy controls. However, there was no considerable difference of IL-17 measured in CSF between the groups. In conclusion, a high activity and consequent consumption of IL-17-producing Th17-cells is suspected in acute IVDH. These findings may indicate an involvement of Th17-cells in the pathogenesis of IVDH and emphasize that these cells might be involved in the interaction of pain, stress and immune reaction. However, based on the findings of this study the development of Th17-cells as a biomarker cannot be recommended, yet.

show abstract

Section: Discussionmentioning

confidence: 99%

Evaluation of the involvement of Th17-cells in the pathogenesis of canine spinal cord injury

et al. 2021

View full text Add to dashboard Cite

show abstract

“…23 In addition to repair cells that deposit granulation tissue, immune cells such as pro-inflammatory macrophages, T lymphocytes, and mast cells have been implicated in poor adult AF healing. 24,48–51 However, mechanistic studies testing the requirement of these cells in healing have not been carried out and the sources of fibrotic repair cells remain largely unidentified. Fibronectin is a fibrotic marker associated with IVD degeneration and has been previously identified via immunostaining in degenerated human IVD tissue.…”

Section: Discussionmentioning

confidence: 99%

Neonatal annulus fibrosus regeneration occurs via recruitment and proliferation of Scleraxis-lineage cells

et al. 2019

View full text Add to dashboard Cite

Intervertebral disc (IVD) injuries are a cause of degenerative changes in adults which can lead to back pain, a leading cause of disability. We developed a model of neonatal IVD regeneration with full functional restoration and investigate the cellular dynamics underlying this unique healing response. We employed genetic lineage tracing in mice using Scleraxis (Scx) and Sonic hedgehog (Shh) to fate-map annulus fibrosus (AF) and nucleus pulposus (NP) cells, respectively. Results indicate functional AF regeneration after severe herniation injury occurs in neonates and not adults. AF regeneration is mediated by Scx-lineage cells that lose ScxGFP expression and adopt a stem/progenitor phenotype (Sca-1, days 3–14), proliferate, and then redifferentiate towards type I collagen producing, ScxGFP+ annulocytes at day 56. Non Scx-lineage cells were also transiently observed during neonatal repair, including Shh-lineage cells, macrophages, and myofibroblasts; however, these populations were no longer detected by day 56 when annulocytes redifferentiate. Overall, repair did not occur in adults. These results identify an exciting cellular mechanism of neonatal AF regeneration that is predominantly driven by Scx-lineage annulocytes.

show abstract

“…In the present study, we found TNF-α was up-regulated in local nucleus cells and peripheral blood [ 28 , 39 ]. This finding is in line with previous studies.…”

Section: Discussionmentioning

confidence: 90%

“…Furthermore, evidence showed that TNF-α is the base of inflammation in IDD process [ 26 ]. Clinical study showed that the level of TNF-α was related to low back pain in patients [ 4 , 27 , 28 ]. Higher TNF-α level indicated suffering more pain.…”

Section: Discussionmentioning

confidence: 99%

Progranulin derived engineered protein Atsttrin suppresses TNF-α-mediated inflammation in intervertebral disc degenerative disease

et al. 2017

View full text Add to dashboard Cite

Atsttrin, an engineered molecule composed of three fragments of progranulin(PGRN), exerts comparable anti-inflammation ability. Intervertebral disc degeneration (IDD) is involved in inflammation in which TNF-α plays a key role. This study aims to examine the effect and the mechanism of Atsttrin in the pathogenesis of intervertebral disc degeneration. For this purpose, we took advantage of murine and human intervertebral disc (IVD) and examined the expression of TNF-α in IVD tissues using immunohistochemistry and TNF-α level in peripheral sera by ELISA assay. Moreover, murine IVD was taken to undergo the Safranin O and HE staining. Furthermore, primary human nucleus pulposus cells were used for immunohistochemistry staining, fluorescent staining, Western Blot, ELISA assay and RT-PCR assay. Herein we found TNF-α expression was elevated in intervertebral disc and peripheral sera in patients with IDD. Interestingly, Atsttrin effectively inhibited TNF-α-mediated catabolism in murine disc by ex vivo study. TNF-α-induced inflammatory cytokines were strongly reduced in presence of Atsttrin in primary human disc. Mechanism study indicated Atsttrin protected against intervertebral disc degeneration by inhibiting TNF-α-induced inflammation. These findings show that Atsttrin is a potential molecular target for disc degenerative diseases.

show abstract

Systemic Inflammatory and Th17 Immune Activation among Patients Treated for Lumbar Radiculopathy Exceeds that of Patients Treated for Persistent Postoperative Neuropathic Pain

Abstract: Differences in Th17 immune activation are seen among radiculopathy and neuropathic pain patients. These cellular and molecular profiles may be translated into biomarkers to improve patient selection for structural spine surgery.

Cited by 10 publications

References 24 publications

Evaluation of the involvement of Th17-cells in the pathogenesis of canine spinal cord injury

Evaluation of the involvement of Th17-cells in the pathogenesis of canine spinal cord injury

Neonatal annulus fibrosus regeneration occurs via recruitment and proliferation of Scleraxis-lineage cells

Progranulin derived engineered protein Atsttrin suppresses TNF-α-mediated inflammation in intervertebral disc degenerative disease

Contact Info

Product

Resources

About