Anti-inflammatory T-cell shift in neuropathic pain

Luchting, Benjamin; Rachinger-Adam, Banafscheh; Heyn, Jens; Hinske, Christian; Kreth, Simone; Azad, Shahnaz Christina

doi:10.1186/s12974-014-0225-0

Cited by 63 publications

(63 citation statements)

References 36 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies found elevated pro-inflammatory factor levels with age [26]. High levels of TNF-α, iNOS, IL-1β, and IFN-γ have been observed when aged MΦ were challenged with IFN-γ or LPS [22, 27, 28]. These findings suggest that aged MΦ remain in a preactivated resting state that enhances their responsiveness to exposure of pro-inflammatory stimuli [29].…”

Section: Discussionmentioning

confidence: 88%

See 1 more Smart Citation

Aging Affects Bone Marrow Macrophage Polarization: Relevance to Bone Healing

Gibon

Loi

Córdova

et al. 2016

Regen. Eng. Transl. Med.

View full text Add to dashboard Cite

Macrophages are an important component of the inflammatory cascade by initiating and modulating the processes leading to tissue regeneration and bone healing. Depending on the local environment, macrophages can be polarized into M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes. In order to assess the effects of aging on macrophage function, bone marrow macrophage polarization using primary bone marrow macrophages (BMMs) from young (8 weeks old) and aged (72 weeks old) wild-type male C57BL/6J mice was analyzed. Fluorescence-activated cell sorting (FACS) analysis (CD11b, iNOS, CD206), qRT-PCR (iNOS, TNF-α, CD206, Arginase 1), and ELISA (TNF-α, IL-1ra) were performed to compare the M1 and M2 phenotypic markers in young and aged mouse macrophages. Once M1 and M2 macrophage phenotypes were confirmed, the results showed that TNF-α mRNA was significantly upregulated in aged M1s after interferon gamma (INF-γ) exposure. Arginase 1 and CD206 mRNA expression were still upregulated with IL4 stimulation in aged macrophages, but to a lesser extend than those from younger animals. TNF-α secretion was also significantly increased in aged M1s compared to young M1s, following lipopolysaccharide (LPS) exposure. However, the IL-1ra secretion did not increase accordingly in aged mice. The results demonstrate that, compared to younger animals, aging of bone marrow derived macrophages increases the resting levels of oxidative stress, and the ratios of pro- to anti-inflammatory markers. These age-related changes in macrophage polarization may explain in part the attenuated response to adverse stimuli and delay in processes such as fracture healing seen in the elderly. Lay Summary Bone healing is a complex process that involves both biological and mechanical factors. Macrophages are key cells that regulate the events involved in bone healing, especially the initial inflammatory phase. In this biological cascade of events, macrophages present as different functional phenotypes including uncommitted (M0), pro-inflammatory (M1), and anti-inflammatory (M2), a process called macrophage polarization. A clear understanding of the effects of aging on macrophage polarization is critical to modulating adverse events such as fractures, atraumatic bone loss, and tissue regeneration in an aging population.

show abstract

Section: Discussionmentioning

confidence: 88%

“…They found decreased IL-1β and TNF-α protein levels in aged M1s, compared to young M1s. Barrett et al [22] showed an increased response to inflammatory stimuli in aged compared to younger rat M1s, with significantly higher levels of TNF-α RNA. However, no M2 polarization was performed in this study.…”

Section: Introductionmentioning

confidence: 99%

Aging Affects Bone Marrow Macrophage Polarization: Relevance to Bone Healing

Gibon

Loi

Córdova

et al. 2016

Regen. Eng. Transl. Med.

View full text Add to dashboard Cite

show abstract

“…69, 79 Consistent with our observation of increased hemopexin in CSF of LBP patients, others have observed a reduction in Th17 T cells in LBP patients and in chronic neuropathic pain patients. 63, 64 The observation that the increase in hemopexin levels in the CSF from patients with painful DD but not in pain-free individuals with DD suggests that nerve injury may play a role in the pathophysiology of painful DD. Due to the association between nerve injury and hemopexin levels, hemopexin was selected for further analysis by ELISA.…”

Section: Discussionmentioning

confidence: 99%

Evidence for a Role of Nerve Injury in Painful Intervertebral Disc Degeneration: A Cross-Sectional Proteomic Analysis of Human Cerebrospinal Fluid

Lim

Anderson

Hari

et al. 2017

The Journal of Pain

View full text Add to dashboard Cite

Intervertebral disc degeneration (DD) is a cause of low back pain (LBP) in some individuals. However, while >30% of adults have DD, LBP only develops in a subset of individuals. To gain insight into the mechanisms underlying non-painful versus painful DD, human cerebrospinal fluid (CSF) was examined using differential expression shotgun proteomic techniques comparing healthy controls, subjects with non-painful DD, and patients with painful DD scheduled for spinal fusion surgery. Eighty-eight proteins were detected, 27 of which were differentially expressed. Proteins associated with DD tended to be related to inflammation (e.g. cystatin C) regardless of pain status. In contrast, most differentially expressed proteins in DD-associated chronic LBP patients were linked to nerve injury (e.g. hemopexin). Cystatin C and hemopexin were selected for further examination by ELISA in a larger cohort. While Cystatin C correlated with DD severity but not pain or disability, hemopexin correlated with pain intensity, physical disability and DD severity. This study demonstrates that CSF can be used to study mechanisms underlying painful DD in humans, and suggests that while painful DD is associated with nerve injury, inflammation itself is not sufficient to develop LBP.

show abstract

“…Serum levels of IL-23/IL-17 are reportedly elevated in periodontitis patients (Qi et al, 2013). IL-23 was the only cytokine reportedly above the detectable limit in human blood of patients with neuropathic pain in a report by Luchting et al (2015). GMCSF is increased in T lymphocytes after L5 nerve transection in mice (Draleau et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Dysregulated TNFα promotes cytokine proteome profile increases and bilateral orofacial hypersensitivity

Zhang

Mashni

et al. 2015

Neuroscience

View full text Add to dashboard Cite

Background: Tumor necrosis factor alpha (TNFα) is increased in patients with headache, neuropathic pain, periodontal and temporomandibular disease. This study and others have utilized TNF receptor 1/2 (TNFR1/2) knockout (KO) animals to investigate the effect of TNFα dysregulation in generation and maintenance of chronic neuropathic pain. The present study determined the impact of TNFα dysregulation in a trigeminal inflammatory compression (TIC) nerve injury model comparing wild-type (WT) and TNFR1/2 KO mice. Methods: Chromic gut suture was inserted adjacent to the infraorbital nerve to induce the TIC model mechanical hypersensitivity. Cytokine proteome profiles demonstrated serology, and morphology explored microglial activation in trigeminal nucleus 10 weeks post. Results: TIC injury induced ipsilateral whisker pad mechanical allodynia persisting throughout the 10-week study in both TNFR1/2 KO and WT mice. Delayed mechanical allodynia developed on the contralateral whisker pad in TNFR1/2 KO mice but not in WT mice. Proteomic profiling 10 weeks after chronic TIC injury revealed TNFα, interleukin-1alpha (IL-1α), interleukin-5 (IL-5), interleukin-23 (IL-23), macrophage inflammatory MIP-1β(MIP-1β), and granulocyte–macrophage colony-stimulating factor (GM-CSF) were increased more than 2-fold in TNFR1/2 KO mice compared to WT mice with TIC. Bilateral microglial activation in spinal trigeminal nucleus was detected only in TNFR1/2 KO mice. p38 mitogen-activated protein kinase (MAPK) inhibitor and microglial inhibitor minocycline reduced hypersensitivity. Conclusions: The results suggest the dysregulated serum cytokine proteome profile and bilateral spinal trigeminal nucleus microglial activation are contributory to the bilateral mechanical hypersensitization in this chronic trigeminal neuropathic pain model in the mice with TNFα dysregulation. Data support involvement of both neurogenic and humoral influences in chronic neuropathic pain.

show abstract

Anti-inflammatory T-cell shift in neuropathic pain

Cited by 63 publications

References 36 publications

Aging Affects Bone Marrow Macrophage Polarization: Relevance to Bone Healing

Aging Affects Bone Marrow Macrophage Polarization: Relevance to Bone Healing

Evidence for a Role of Nerve Injury in Painful Intervertebral Disc Degeneration: A Cross-Sectional Proteomic Analysis of Human Cerebrospinal Fluid

Dysregulated TNFα promotes cytokine proteome profile increases and bilateral orofacial hypersensitivity

Contact Info

Product

Resources

About