T Cells as an Emerging Target for Chronic Pain Therapy

Laumet, Geoffroy; Ma, Jiacheng; Robison, Alfred J.; Kumari, Susmita; Heijnen, Cobi J.; Kavelaars, Annemieke

doi:10.3389/fnmol.2019.00216

Cited by 82 publications

(88 citation statements)

References 156 publications

(278 reference statements)

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“…The blockade of TNF with etanercept delivered by intrathecal or systemic routes was able to reverse the persistent nociception evoked by TNF in the DRG. It has been demonstrated that T cells may be involved in the transition from acute to chronic pain after inflammatory stimulus, indicating a role in pain maintenance of several inflammatory diseases (45). However, in our model, the number of mononuclear cells, which includes monocytes and lymphocytes, present after AIA did not differ from the basal level of cells from cavities injected with PBS.…”

Section: Discussioncontrasting

confidence: 71%

Sensory Ganglia-Specific TNF Expression Is Associated With Persistent Nociception After Resolution of Inflammation

et al. 2020

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systemic injection of etanercept, an agent clinically utilized for TNF neutralization, at day 7 post arthritis induction, alleviated the persistent joint hyperalgesia by specific action in DRG. Our data suggest that neuroinflammation in DRG after the resolution of acute joint inflammation drives continuous neural sensitization resulting in persistent joint nociception in a TNF-dependent mechanism.

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Section: Discussioncontrasting

confidence: 71%

Sensory Ganglia-Specific TNF Expression Is Associated With Persistent Nociception After Resolution of Inflammation

et al. 2020

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“…Changes in predicted blood cell counts were also found in the FM dataset, in which we observed a decrease in predicted CD4+ naive cells in patients and an inverse association between CD8+ T cells and NK cells and the severity of the disease symptoms, assessed as BPI_interference and PCS. Collectively, these results sustain the role of the immune system in painrelated conditions (88).…”

Section: Discussionsupporting

confidence: 64%

Analysis of Epigenetic Age Predictors in Pain-Related Conditions

Kwiatkowska

Bacalini

Sala

et al. 2020

Front. Public Health

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Chronic pain prevalence is high worldwide and increases at older ages. Signs of premature aging have been associated with chronic pain, but few studies have investigated aging biomarkers in pain-related conditions. A set of DNA methylation (DNAm)-based estimates of age, called "epigenetic clocks," has been proposed as biological measures of age-related adverse processes, morbidity, and mortality. The aim of this study is to assess if different pain-related phenotypes show alterations in DNAm age. In our analysis, we considered three cohorts for which whole-blood DNAm data were available: heat pain sensitivity (HPS), including 20 monozygotic twin pairs discordant for heat pain temperature threshold; fibromyalgia (FM), including 24 cases and 20 controls; and headache, including 22 chronic migraine and medication overuse headache patients (MOH), 18 episodic migraineurs (EM), and 13 healthy subjects. We used the Horvath's epigenetic age calculator to obtain DNAm-based estimates of epigenetic age, telomere length, levels of 7 proteins in plasma, number of smoked packs of cigarettes per year, and blood cell counts. We did not find differences in epigenetic age acceleration, calculated using five different epigenetic clocks, between subjects discordant for pain-related phenotypes. Twins with high HPS had increased CD8+ T cell counts (nominal p = 0.028). HPS thresholds were negatively associated with estimated levels of GDF15 (nominal p = 0.008). FM patients showed decreased naive CD4+ T cell counts compared with controls (nominal p = 0.015). The severity of FM manifestations expressed through various evaluation tests was associated with decreased levels of leptin, shorter length of telomeres, and reduced CD8+ T and natural killer cell counts (nominal p < 0.05), while the duration of painful symptoms was positively associated with telomere length (nominal p = 0.034). No differences in DNAm-based estimates were detected for MOH or EM compared with controls. In summary, our study suggests Kwiatkowska et al. Epigenetic Age in Pain that HPS, FM, and MOH/EM do not show signs of epigenetic age acceleration in whole blood, while HPS and FM are associated with DNAm-based estimates of immunological parameters, plasma proteins, and telomere length. Future studies should extend these observations in larger cohorts.

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“…As such, proliferation and activation of immune cells may be accompanied with increased expression of opioid receptors while the toxic effects of inflammatory and oxidative stress mechanisms may damage cell membranes thereby increasing shedding of the opioid receptors into the plasma. Some T-cell subsets release cytokines and EOS peptides/receptors that can promote, suppress, or resolve pain [60,61]. Moreover, also endomorphin 2 may be produced by immunocytes in inflamed subcutaneous tissues, whereas this peptide is almost absent in non-inflamed tissue [62].…”

Section: Discussionmentioning

confidence: 99%

The Endogenous Opioid System in Schizophrenia and Treatment Resistant Schizophrenia: Increased Plasma Endomorphin 2, and κ and μ Opioid Receptors Are Associated with Interleukin-6

et al. 2020

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Background: activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS) plays a key role in schizophrenia (SCZ) and treatment resistant SCZ. There are only a few data on immune and endogenous opioid system (EOS) interactions in SCZ and treatment resistant SCZ. Methods: we examined serum β-endorphin, endomorphin-2 (EM2), mu-opioid (MOR) and kappa-opioid (KOR) receptors, and interleukin (IL)-6 and IL-10 in 60 non responders to treatment (NRTT), 55 partial RTT (PRTT) and 43 normal controls. Results: serum EM2, KOR, MOR, IL-6 and IL-10 were significantly increased in SCZ as compared with controls. β-endorphin, EM2, MOR and IL-6 were significantly higher in NRTT than in PRTT. There were significant correlations between IL-6, on the one hand, and β-endorphin, EM2, KOR, and MOR, on the other, while IL-10 was significantly correlated with MOR only. A large part of the variance in negative symptoms, psychosis, hostility, excitation, mannerism, psychomotor retardation and formal thought disorders was explained by the combined effects of EM2 and MOR with or without IL-6 while increased KOR was significantly associated with all symptom dimensions. Increased MOR, KOR, EM2 and IL-6 were also associated with neurocognitive impairments including in episodic, semantic and working memory and executive functions. Conclusion: the EOS contributes to SCZ symptomatology, neurocognitive impairments and a non-response to treatment. In SCZ, EOS peptides/receptors may exert CIRS functions, whereas increased KOR levels may contribute to the pathophysiology of SCZ and EM2 and KOR to a non-response to treatment.

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T Cells as an Emerging Target for Chronic Pain Therapy

Cited by 82 publications

References 156 publications

Sensory Ganglia-Specific TNF Expression Is Associated With Persistent Nociception After Resolution of Inflammation

Sensory Ganglia-Specific TNF Expression Is Associated With Persistent Nociception After Resolution of Inflammation

Analysis of Epigenetic Age Predictors in Pain-Related Conditions

The Endogenous Opioid System in Schizophrenia and Treatment Resistant Schizophrenia: Increased Plasma Endomorphin 2, and κ and μ Opioid Receptors Are Associated with Interleukin-6

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