Anti-nociceptive effect of IL-12p40 in a rat model of neuropathic pain

Chen, I.-Fang; Khan, Junad; Noma, Noboru; Hadlaq, Emad M; Teich, Sorin; Benoliel, Rafael; Eliav, Eli

doi:10.1016/j.cyto.2013.03.021

Cited by 12 publications

(6 citation statements)

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“…IL-12p70, also referred to as IL-12, is a pro-inflammatory cytokine secreted by activated hematopoietic phagocytic cells; Chen et al (39) investigated pain response following systemic administration of IL-12p70 and IL-12p40 homodimer and found that IL-12p40 exhibited significant anti-nociceptive effects in a rat model of chronic NP. The present study found that IL12B was dysregulated in brain tissues of NP mice, which is consistent with previous studies (37-39). This dysregulation may be effectuated by miRNA, one of which, miR-208a-5p , was found in the miRNA-target gene-pathway regulatory network, to target IL12B .…”

Section: Discussionmentioning

confidence: 99%

Identification of candidate genes and miRNAs associated with neuropathic pain induced by spared nerve injury

et al. 2019

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Neuropathic pain (NP) is a complex, chronic pain condition caused by injury or dysfunction affecting the somatosensory nervous system. This study aimed to identify crucial genes and miRNAs involved in NP. Microarray data (access number GSE91396) were downloaded from the Gene Expression Omnibus (GEO). Murine RNA-seq samples from three brain regions [nucleus accumbens, (NAc); medial prefrontal cortex, (mPFC) and periaqueductal gray, (PAG)] were compared between the spared nerve injury (SNI) model and a sham surgery. After data normalization, differentially expressed RNAs were screened using the limma package and functional enrichment analysis was performed with Database for Annotation, Visualization and Integrated Discovery. The microRNA (miRNA/miR)-mRNA regulatory network and miRNA-target gene-pathway regulatory network were constructed using Cytoscape software. A total of 2,776 differentially expressed RNAs (219 miRNAs and 2,557 mRNAs) were identified in the SNI model compared with the sham surgery group. A total of two important modules (red and turquoise module) were found to be related to NP using weighed gene co-expression network analysis (WGCNA) for the 2,325 common differentially expressed RNAs in three brain regions. The differentially expressed genes (DEGs) in the miRNA-mRNA regulatory network were significantly enriched in 21 Gene Ontology terms and five pathways. A total of four important DEGs ( CXCR2 , IL12B , TNFSF8 and GRK1 ) and five miRNAs ( miR-208a-5p , miR-7688-3p , miR-344f-3p , miR-135b-3p and miR-135a-2-3p ) were revealed according to the miRNA-target gene-pathway regulatory network to be related to NP. Four important DEGs ( CXCR2 , IL12B , TNFSF8 and GRK1 ) and five miRNAs ( miR-208a-5p , miR-7688-3p , miR-344f-3p , miR-135b-3p and miR-135a-2-3p ) were differentially expressed in SNI, indicating their plausible roles in NP pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Identification of candidate genes and miRNAs associated with neuropathic pain induced by spared nerve injury

et al. 2019

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“…Although the roles of TNF-α and IL-1β in the development of pain are well-established, the contributions of IL-7 and IL-12 to pain are controversial (56-59). Clinically, IL-7 transcription and expression were shown to increase in intervertebral disc cells in patients with low back pain (59).…”

Section: Discussionmentioning

confidence: 99%

“…Serum levels of IL-12 are also elevated in women with work-related musculoskeletal pain (58). In contrast, administration of IL-12 subcutaneously reduces mechanical allodynia and hyperalgesia for up to 4 hours when given after a painful chronic constriction to the sciatic nerve (56). In the current study, serum concentrations of both IL-7 and IL-12 positively correlate to mechanical hyperalgesia at day 1 after a nerve root compression (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Salmon-derived thrombin inhibits development of chronic pain through an endothelial barrier protective mechanism dependent on APC

et al. 2016

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Many neurological disorders are initiated by blood-brain barrier breakdown, which potentiates spinal neuroinflammation and neurodegeneration. Peripheral neuropathic injuries are known to disrupt the blood-spinal cord barrier (BSCB) and to potentiate inflammation. But, it is not known whether BSCB breakdown facilitates pain development. In this study, a neural compression model in the rat was used to evaluate relationships among BSCB permeability, inflammation and pain-related behaviors. BSCB permeability increases transiently only after injury that induces mechanical hyperalgesia, which correlates with serum concentrations of pro-inflammatory cytokines, IL-7, IL-12, IL-1α and TNF-α. Mammalian thrombin dually regulates vascular permeability through PAR1 and activated protein C (APC). Since thrombin protects vascular integrity through APC, directing its affinity towards protein C, while still promoting coagulation, might be an ideal treatment for BSCB-disrupting disorders. Salmon thrombin, which prevents the development of mechanical allodynia, also prevents BSCB breakdown after neural injury and actively inhibits TNF-α-induced endothelial permeability in vitro, which is not evident the case for human thrombin. Salmon thrombin’s production of APC faster than human thrombin is confirmed using a fluorogenic assay and APC is shown to inhibit BSCB breakdown and pain-related behaviors similar to salmon thrombin. Together, these studies highlight the impact of BSCB on pain and establish salmon thrombin as an effective blocker of BSCB, and resulting nociception, through its preferential affinity for protein C.

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“…In this sense, it would be insightful to investigate whether changes in IL-12p70 after exercise training in migraine patients are paralleled by changes in IL-12p40. In fact, IL-12p40 has been shown to promote antinociception in animal models of neuropathic pain [45]. Thus, the involvement of the IL-12 family of cytokines in migraine is worthy of further investigation.…”

Section: Discussionmentioning

confidence: 99%

Exercise-Induced Change in Plasma IL-12p70 Is Linked to Migraine Prevention and Anxiolytic Effects in Treatment-Naïve Women: A Randomized Controlled Trial

Oliveira

Bachi²,

Ribeiro

et al. 2017

Neuroimmunomodulation

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Objective: To conduct a randomized controlled trial to evaluate the effect of a 12-week aerobic exercise program for migraine prevention, plasma cytokines concentrations (TNF-α, interleukin [IL]-1β, IL-6, IL-8, IL-10, and IL-12p70), and anxiety in women with migraine. Methods: Women with episodic migraine (ICHD-II), aged between 20 and 50 years, who had never taken any prophylactic medication, and were physically inactive in the past 12 months were recruited from the university’s hospital and a tertiary headache clinic between March 2012 and March 2015. Migraine attacks were recorded in headache diaries, cytokines were quantified by flow cytometry, and anxiety was assessed by the 7-item General Anxiety Disorder (GAD-7) scale. Blood sampling and psychometric interviews were undertaken on headache-free days. Results: Twenty participants ([mean ± SD] age 33.8 ± 10.5; BMI 26 ± 5.2) were randomly assigned and received intervention (“trained”: n = 10) or entered on a waitlist (“inactive”: n = 10). There were no differences between groups regarding patients’ characteristics and baseline data. Days with migraine (p = 0.001), IL-12p70 levels (p = 0.036), and GAD-7 score (p = 0.034) were significantly reduced in the trained group after the intervention period, but there were no significant changes in these variables in the inactive group. There was no change in the levels of the other cytokines in either group. There were positive correlations between a reduction in IL-12p70 level and a reduction in the number of days with migraine (R² = 0.19, p = 0.045), and GAD-7 score (R² = 0.53, p < 0.001). Conclusion: The clinical and psychological therapeutic effects of aerobic exercise in treatment-naïve women with migraine may involve the downregulation of IL-12p70.

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Anti-nociceptive effect of IL-12p40 in a rat model of neuropathic pain

Cited by 12 publications

References 50 publications

Identification of candidate genes and miRNAs associated with neuropathic pain induced by spared nerve injury

Identification of candidate genes and miRNAs associated with neuropathic pain induced by spared nerve injury

Salmon-derived thrombin inhibits development of chronic pain through an endothelial barrier protective mechanism dependent on APC

Exercise-Induced Change in Plasma IL-12p70 Is Linked to Migraine Prevention and Anxiolytic Effects in Treatment-Naïve Women: A Randomized Controlled Trial

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