The relationship between pro-inflammatory cytokines and pain, appetite and fatigue in patients with advanced cancer

Paulsen, Ørnulf; Laird, Barry; Aass, Nina; Lea, Tor; Fayers, Peter; Kaasa, Stein; Klepstad, Pål

doi:10.1371/journal.pone.0177620

Cited by 91 publications

(80 citation statements)

References 60 publications

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“…2 A randomized trial reported that a low skeletal muscle mass (sarcopenia) due to cachexia was associated with depression and quality of life in patients with advanced cancer. 16 Other studies on cancer patients revealed that systemic inflammation or elevated CRP levels were related to pain, anorexia, dyspnoea, fatigue, sleep disturbance, activities of daily living disabilities, and survival, [8][9][10][11][12][13][14][15] that these symptoms rarely existed in isolation, 11,13,39 and that pain, fatigue, and sleep disturbance were the basis of a symptom cluster in combination with reduced physical function. 14 A cross-sectional study showed a higher physical and psychological symptom burden (including pain, fatigue, sleep disturbance, distress, and anxiety) in patients with cancer cachexia, which increased with the stages of cachexia, and these findings emphasized the importance of screening for multiple co-occurring symptoms in cachexia patients.…”

Section: Discussionmentioning

confidence: 99%

“…sleep disturbance, depression, and cognitive dysfunction, as well as physical disorders in patients with cancer. [7][8][9][10][11][12][13][14][15][16] Nevertheless, studies on CNS regulation in cancer cachexia have been limited to investigations on the systemic levels of neuromodulatory peptides, such as appetite-regulating hormones. 2 Moreover, 'sickness behaviour' has been reported in infected mammals and recognized as a symptom cluster, including fatigue, sleep disturbance, depression, and cognitive dysfunction, which is associated with systemic inflammation and its impact on the CNS.…”

Section: Introductionmentioning

confidence: 99%

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C‐reactive protein, delirium, and other psychological symptoms among patients with advanced cancer

Amano¹,

Hatano

Matsuda

et al. 2020

JCSM Clinical Reports

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BackgroundIt remains unclear whether a relationship exists between elevated C‐reactive protein (CRP) levels and delirium. The primary aim was to investigate the relationship between CRP and delirium in advanced cancer.MethodsThis study was a multicenter prospective cohort study conducted in palliative care units. At baseline, the physicians diagnosed delirium. On the seventh day, they evaluated whether new delirium had occurred. Subjects were divided into four groups according to CRP levels. We assessed the associations between CRP levels and proportions of delirium. To evaluate the relationship between CRP and delirium, adjusted odd ratios (ORs) and 95% confidence intervals (CIs) were calculated in the logistic models.ResultsAmong 1896 patients, 1354 patients were eligible for analyses. We classified them into four groups: low (CRP < 1 mg/dl) (n = 170), moderate (1 ≤ CRP < 5 mg/dl) (n = 453), high (5 ≤ CRP < 10 mg/dl) (n = 334), and very high (10 mg/dl ≤ CRP) (n = 397). The incidence of delirium significantly increased with increasing CRP levels (P = 0.02). In model 1, significantly higher adjusted ORs than in the low CRP group were observed in the high CRP and very high CRP groups (1.63 [95% CI 1.06–2.50], P = 0.03; 1.72 [95% CI 1.13–2.62], P = 0.01, respectively). In model 2, a significantly higher adjusted OR than in the low CRP group was observed in the very high CRP group (1.61 [95% CI 1.05–2.45], P = 0.03).ConclusionsRelationships existed between elevated CRP levels and delirium.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

C‐reactive protein, delirium, and other psychological symptoms among patients with advanced cancer

Amano¹,

Hatano

Matsuda

et al. 2020

JCSM Clinical Reports

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“…TNF-α is major regulator of early degenerative alterations during the process of peripheral nerve damage [38]. In addition, it has also been demonstrated that TNF-α could induce ectopic activity, macrophage enrichment, and axonal damage in peripheral nerves [39]. At present, the most obvious evidence for the involvement of proinflammatory cytokines in the increase of pain comes from research of IL-1β and TNF-α in the spinal cord.…”

Section: Discussionmentioning

confidence: 99%

Administration of Curcumin Alleviates Neuropathic Pain in a Rat Model of Brachial Plexus Avulsion

Xie¹,

Xie²,

Kang³

et al. 2019

Pharmacology

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Background/Aims: Brachial plexus avulsion (BPA) generally causes a chronic persistent pain that lacks efficacious treatment. Curcumin has been found to possess anti-inflammatory abilities. However, little is known about the mechanisms and effects of curcumin in an animal model of BPA. Methods: Mechanical withdrawal thresholds (MWT) were examined by von Frey filaments. Cold allodynia was tested by the acetone spray test. The levels of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in rat spinal cords were analyzed by the enzyme-linked immunosorbent assay, and the expression levels of c-Fos and nerve growth factor (NGF) were measured by Western blot. The expression level of glial fibrillary acidic protein (GFAP) was observed by immunofluorescence and Western blot. Results: After curcumin treatment, the MWT showed a significant increase when compared to the BPA group on both hind paws. A remarkable decrease of paw-withdrawal response frequency was observed compared with the BPA group. In addition, curcumin treatment significantly decreased the levels of TNF-α and IL-6 in rat spinal cords that were exceedingly upregulated in the BPA group. The protein levels of c-Fos and NGF were decreased by treatment with curcumin compared with the corresponding protein levels in the BPA group. Besides, curcumin reduced the number of GFAP positive cells and GFAP expression. Conclusions: Our findings suggest that curcumin significantly extenuates the BPA-induced pain and inflammation by reducing the expression level of proinflammatory cytokines and pain-associated proteins and inhibiting the activity of astrocytes.

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“…Different opioids show different effects on the immune system such as immunostimulatory, immunosuppressive, or dual effect 26 . However, how they affect the different cytokines is not well defined 27 . Immunosuppressive activity depends on the type of the opioid, independent of the potency or the duration of action 28 .…”

Section: Discussionmentioning

confidence: 99%

Acute Immunomodulatory Effects of Fentanyl and its Three New Analogues in Swiss Albino Mice

Yadav

Bhattacharya

2017

Def. Life. Sc. Jl.

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Fentanyl is a potent synthetic opioid analgesic. However, due to its several limitations, new analogues are being synthesised for better pain management. We have earlier reported the synthesis and bio-efficacy of fentanyl and its eight new analogues (1-8) in mice. Among eight analogues tested, N- (1-(2-phenoxyethyl)-4-piperidinyl) propionanilide (2), N-isopropyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (5), and N-t-butyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (6) were found to be more effective and less toxic compared to fentanyl. Therapeutic efficacy of fentanyl and its analogues are known to be compromised due to many adverse effects, including alterations in the immune system. Therefore, the present study was undertaken to assess the acute effect of fentanyl and its three analogues (2, 5, and 6) on plasma levels of different pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and anti-inflammatory cytokines such as interleukin-10 (IL-10) at different time points. Mice were intraperitoneally treated with 0.50 LD 50 of the compounds and cytokines were measured 1 h, 2 h, 4 h, and 24 h post-exposure. Compared to control, none of the treatments produced any change in TNF-α and IL-1β levels. However, IL-6 levels were significantly elevated between 1 h to 2 h post-exposure in fentanyl and analogue 2 treated groups. Further, IL-10 levels were found to be significantly increased in fentanyl, analogue 2, and 6 treated groups at 1 h and 2 h post-exposure. Pretreatment of naltrexone (opioid receptor antagonist) blocked the effects of fentanyl, confirming that its effects were opioid receptor-dependent. However, effect of naltrexone on analogue 2 and 6 was not conclusively evidenced, indicating that immunomodulatory changes caused by the analogues could have some additional implications as well. The present study reveals undesirable effects of fentanyl and its new analogues on cytokines homeostasis, thereby limiting their use in pain management.

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The relationship between pro-inflammatory cytokines and pain, appetite and fatigue in patients with advanced cancer

Cited by 91 publications

References 60 publications

C‐reactive protein, delirium, and other psychological symptoms among patients with advanced cancer

C‐reactive protein, delirium, and other psychological symptoms among patients with advanced cancer

Administration of Curcumin Alleviates Neuropathic Pain in a Rat Model of Brachial Plexus Avulsion

Acute Immunomodulatory Effects of Fentanyl and its Three New Analogues in Swiss Albino Mice

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