Interleukin-6: an emerging regulator of pathological pain

Zhou, Ya‐Qun; Liu, Zheng; Liu, Zhiheng; Chen, Shuping; Li, Man; Shahveranov, Allahverdi; Ye, Dawei; Tian, Yuan

doi:10.1186/s12974-016-0607-6

Cited by 316 publications

(262 citation statements)

References 118 publications

(89 reference statements)

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“…There is evidence that the neutralization of IL-6 leads to the attenuation of hypersensitivity symptoms. 94 Our results provide evidence that repeatedly administered CCR1 antagonist is able to relieve pain by reducing the activation of microglia, macrophages, neutrophils and lymphocytes in the spinal cord and/or DRG and so by inducing beneficial changes in the levels of immunological factors with pronociceptive (IL-1b, IL-6, and IL-18) and antinociceptive (IL-1RA) properties.…”

Section: Discussionmentioning

confidence: 57%

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

et al. 2020

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Summary A growing body of evidence has indicated that the release of nociceptive factors, such as interleukins and chemokines, by activated immune and glial cells has crucial significance for neuropathic pain generation and maintenance. Moreover, changes in the production of nociceptive immune factors are associated with low opioid efficacy in the treatment of neuropathy. Recently, it has been suggested that CC chemokine receptor type 1 (CCR1) signaling is important for nociception. Our study provides evidence that the development of hypersensitivity in rats following chronic constriction injury (CCI) of the sciatic nerve is associated with significant up‐regulation of endogenous CCR1 ligands, namely, CCL2, CCL3, CCL4, CCL6, CCL7 and CCL9 in the spinal cord and CCL2, CCL6, CCL7 and CCL9 in dorsal root ganglia (DRG). We showed that single and repeated intrathecal administration of J113863 (an antagonist of CCR1) attenuated mechanical and thermal hypersensitivity. Moreover, repeated administration of a CCR1 antagonist enhanced the analgesic properties of morphine and buprenorphine after CCI. Simultaneously, repeated administration of J113863 reduced the protein levels of IBA‐1 in the spinal cord and MPO and CD4 in the DRG and, as a consequence, the level of pronociceptive factors, such as interleukin‐1β (IL‐1β), IL‐6 and IL‐18. The data obtained provide evidence that CCR1 blockade reduces hypersensitivity and increases opioid‐induced analgesia through the modulation of neuroimmune interactions.

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Section: Discussionmentioning

confidence: 57%

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

et al. 2020

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“…158 IL-6 levels were found to increase in macrophages near the sciatic nerve and DRGs of mice after vincristine treatment. 159 The addition of an anti-IL-6 antibody, which prevents binding of IL-6 to its receptor (IL-6R), reduced mechanical allodynia after its development.…”

Section: Second Messenger Pathwaysmentioning

confidence: 87%

Ion channels and neuronal hyperexcitability in chemotherapy-induced peripheral neuropathy

Aromolaran

Goldstein

2017

Mol Pain

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Cancer is the second leading cause of death worldwide and is a major global health burden. Significant improvements in survival have been achieved, due in part to advances in adjuvant antineoplastic chemotherapy. The most commonly used antineoplastics belong to the taxane, platinum, and vinca alkaloid families. While beneficial, these agents are frequently accompanied by severe side effects, including chemotherapy-induced peripheral neuropathy (CPIN). While CPIN affects both motor and sensory systems, the majority of symptoms are sensory, with pain, tingling, and numbness being the predominant complaints. CPIN not only decreases the quality of life of cancer survivors but also can lead to discontinuation of treatment, thereby adversely affecting survival. Consequently, minimizing the incidence or severity of CPIN is highly desirable, but strategies to prevent and/or treat CIPN have proven elusive. One difficulty in achieving this goal arises from the fact that the molecular and cellular mechanisms that produce CPIN are not fully known; however, one common mechanism appears to be changes in ion channel expression in primary afferent sensory neurons. The processes that underlie chemotherapy-induced changes in ion channel expression and function are poorly understood. Not all antineoplastic agents directly affect ion channel function, suggesting additional pathways may contribute to the development of CPIN Indeed, there are indications that these drugs may mediate their effects through cellular signaling pathways including second messengers and inflammatory cytokines. Here, we focus on ion channelopathies as causal mechanisms for CPIN and review the data from both pre-clinical animal models and from human studies with the aim of facilitating the development of appropriate strategies to prevent and/or treat CPIN.

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“…On the other hand, it has been proposed that insufficient levels of vitamin D might be an unknown reason for initiation and augmentation of pain sensitization, its severity and neuromuscular dysfunction in the subjects who suffer from chronic pain; if so, supplementation with this vitamin can be helpful in improving pain. In this regard, any interventional procedure that is thought to blunt these pathways could act as a pain relieving agent . The role of 1,25 (OH)2 D in modifying genetic pathways in the target cells is performed via its nuclear receptor or vitamin D receptor (VDR).…”

Section: Discussionmentioning

confidence: 99%

Serum Vitamin D Status in a Group of Migraine Patients Compared With Healthy Controls: A Case–Control Study

et al. 2018

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Objective The association between serum vitamin D and migraine is investigated in this research.s Background Although the pathogenesis of migraine headache is not fully understood, the possible role of inflammation and disturbed immune system has been proposed; thus, higher levels of vitamin D might reduce the risk of migraine. However, the results of related studies have been inconclusive. Methods Seventy healthy individuals and 70 age‐ and sex‐matched migraineurs (34 chronic and 36 episodic migraineurs), diagnosed according to the International Headache Society criteria (ICHD‐IIIβ), were recruited. After obtaining baseline data and assessing migraine disability, a 30‐day headache diary was given to the participants. Blood samples were obtained and 25(OH)D serum concentrations were determined using ELISA techniques. Serum 25(OH)D under 20, 20–29, and 30–100 ng/mL were considered deficient, insufficient, and sufficient, respectively. The applied statistical tests for between‐group comparisons include independent‐sample t‐test, chi‐square, and analysis of variance. Multiple regression analysis was also performed to identify the possible risk factors of migraine headache. Results Migraine patients had significantly lower mean (SD) of serum VitD (30 (16) ng/mL) than healthy subjects (43 (19) ng/mL) (P < .001). The number (%) of subjects with VitD deficiency and insufficiency was significantly higher among the migraineurs (36 (53.7%)) than the controls (18 (26.1%)) (P < .0001). A significant negative association between migraine headache and serum VitD was detected in the fully adjusted multiple regression models when comparing the third and the highest serum 25(OH)D quartiles with the lowest (OR = 0.20; 95% CI = 0.05–0.77; OR = 0.17; 95% CI = 0.04–0.64, respectively, P for trend = .009). For each 5 ng/mL increase in serum 25(OH)D, there was a 22% odds decrease in the odds of migraine (OR = 0.78; 95% CI = 0.68–0.90; P = .001). Conclusion We have found that a higher level of serum VitD (between 50 to less than 100 ng/mL) among a sample of the Iranian population is associated with 80–83% lower odds of migraine headache than those with serum 25(OH)D levels below 20 ng/mL. However, there is a need for well‐designed clinical trials to investigate beneficial effects of increased serum 25(OH)D on lower risk of migraine.

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Interleukin-6: an emerging regulator of pathological pain

Cited by 316 publications

References 118 publications

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

Ion channels and neuronal hyperexcitability in chemotherapy-induced peripheral neuropathy

Serum Vitamin D Status in a Group of Migraine Patients Compared With Healthy Controls: A Case–Control Study

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