Does the vagus nerve inform the brain about preclinical tumours and modulate them?

Gidron, Yori; Perry, Hugh; Glennie, Martin J.

doi:10.1016/s1470-2045(05)70096-6

Cited by 100 publications

(84 citation statements)

References 31 publications

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“…remains to be completely elucidated. It has been proposed that proinflammatory cytokines could be involved (25), but such interaction occurs locally rather than systemically because hepatic vagotomy does not appear to mediate IL-1-induced anorexia (41). Supporting the interplay between the vagus nerve and proinflammatory cytokines, the accumulation of brain tryptophan, frequently characterizing the course of chronic diseases and yielding to increased serotonin synthesis and oxidative stress, appears to be influenced by sympathetic activity (65).…”

Section: Autonomic Nervous Systemmentioning

confidence: 99%

Neural control of the anorexia-cachexia syndrome

Laviano¹,

Inui²,

Marks³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

111

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cachexia syndrome is a debilitating clinical condition characterizing the course of chronic diseases, which heavily impacts on patients' morbidity and quality of life, ultimately accelerating death. The pathogenesis is multifactorial and reflects the complexity and redundancy of the mechanisms controlling energy homeostasis under physiological conditions. Accumulating evidence indicates that, during disease, disturbances of the hypothalamic pathways controlling energy homeostasis occur, leading to profound metabolic changes in peripheral tissues. In particular, the hypothalamic melanocortin system does not respond appropriately to peripheral inputs, and its activity is diverted largely toward the promotion of catabolic stimuli (i.e., reduced energy intake, increased energy expenditure, possibly increased muscle proteolysis, and adipose tissue loss). Hypothalamic proinflammatory cytokines and serotonin, among other factors, are key in triggering hypothalamic resistance. These catabolic effects represent the central response to peripheral challenges (i.e., growing tumor, renal, cardiac failure, disrupted hepatic metabolism) that are likely sensed by the brain through the vagus nerve. Also, disease-induced changes in fatty acid oxidation within hypothalamic neurons may contribute to the dysfunction of the hypothalamic melanocortin system. Ultimately, sympathetic outflow mediates, at least in part, the metabolic changes in peripheral tissues. Other factors are likely involved in the pathogenesis of the anorexia-cachexia syndrome, and their role is currently being elucidated. However, available evidence shows that the constellation of symptoms characterizing this syndrome should be considered, at least in part, as different phenotypes of common neurochemical/metabolic alterations in the presence of a chronic inflammatory state. melanocortin; cytokines; serotonin; malonyl-coenzyme A; vagus nerve; sympathetic output THE ANOREXIA-CACHEXIA SYNDROME is a debilitating condition characterizing the clinical journey of patients suffering from chronic diseases including cancer, chronic obstructive pulmonary disease, tuberculosis, chronic heart failure, and end-stage renal insufficiency (64). As an experimental model, it represents a reliable and unique tool for the investigation of the mechanisms regulating energy intake and homeostasis. Beyond its relevance to human physiology, this syndrome impacts on clinical practice since it is highly prevalent and negatively influences patients' morbidity, mortality (66), and quality of life (57).The anorexia-cachexia syndrome is clinically characterized by a number of signs and symptoms interfering with energy intake (i.e., reduced appetite, early satiety, changes in taste/ smell) and affecting nutritional status (i.e., increased metabolic rate, weight loss, hormonal alterations, muscle and adipose tissue wasting, functional impairment, fatigue). At the biochemical and molecular levels, the main features of the anorexia-cachexia syndrome are the profound alterations of brain neurochemis...

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Section: Autonomic Nervous Systemmentioning

confidence: 99%

Neural control of the anorexia-cachexia syndrome

Laviano¹,

Inui²,

Marks³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

111

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“…ANS controls most of the viscera, and many solid cancers are formed in the same viscera [3,4]. Consequently, recent studies have revealed autonomic dysfunction in cancer patients [5].…”

Section: Introductionmentioning

confidence: 99%

Influence of Cancer Severity and Functional Status of Cancer on Cardiac Parasympathetic Indicators

Bijoor

Banerjee

Subbalakshmi

2017

Asian J Pharm Clin Res

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Objective: To investigate the influence of cancer severity and functional status of cancer patients on cardiac parasympathetic indicators. Methods:A total of 267 patients with a fresh clinical diagnosis of solid malignant tumor not yet put on cancer therapy and 250 controls matched for age, sex of study subjects were included. Severity of cancer was defined based on the American Joint Committee on Cancer staging. Accordingly, study subjects were subdivided into early stage (Stage I and II combined) and advanced stage (Stage III and IV combined). In cancer patients, the Eastern Cooperative Oncology Group (ECOG) performance score and the Faces Pain Scale score (FPS) was noted. Two indicators of vagal function, expiratory:inspiratory ratio (E:I ratio) and root mean square of successive N-N interval difference (r-MSSD) were included. E:I ratio during deep breathing at six respiratory cycles/minute and r-MSSD at rest was obtained from 1 minute lead II electrocardiogram. Data were analyzed by applying suitable statistical tests. p≤0.05 was considered significant.Results: R-MSSD and E:I ratio was significantly reduced in the early and advanced stage of cancer compared to controls (p≤0.0001). r-MSSD and E:I ratio was significantly reduced in advanced stage compared to the early stage of cancer (p≤0.0001). r-MSSD and E:I ratio was significantly different in subgroups of stages of cancer and controls (p≤0.0001). In cancer patients, r-MSSD was negatively correlated with ECOG and FPS score (p≤0.0278, p≤0.0100). Conclusion:Severity of cancer affects vagal function. However, r-MSSD alone was associated with functional status (ECOG, FPS) of cancer patients.

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“…Vagal nerve activity is inversely related to and inhibits all these three mechanisms (17)(18)(19)(20)(21). Based on converging evidence, Gidron et al (22) hypothesized that vagal nerve activity may modulate tumor growth, and if this model is valid, might become a variable that could be used as a prognostic factor and could be therapeutically manipulated. The vagal nerve activity index, i.e., heart rate variability (HRV), represents the time differences between successive heartbeats (also known as the beat-to-beat intervals), and is synonymous with RR variability.…”

Section: Introductionmentioning

confidence: 99%

The relationship between vagal nerve activity and clinical outcomes in prostate and non-small cell lung cancer patients

Couck¹,

Brummelen²,

Schallier³

et al. 2013

Oncology Reports

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Abstract. Recent studies suggest that vagal nerve activity, indexed by heart rate variability (HRV), could have a prognostic role in cancer. However, most studies did not control adequately for confounders and included cardiac patients. Furthermore, the validity of this prognostic role needs to be tested in different types of cancer. The present study tested the prognostic role of HRV in prostate cancer (PC) and non-small cell lung cancer (NSCLC) patients, using a historical prospective design. HRV was derived from brief 10 sec ECGs obtained at approximately the time of diagnosis in 113 PC patients and 133 NSCLC patients. Outcomes included prostate-specific antigen (PSA) at 6 and 24 months in PC, and overall survival (OS) (for the full sample) and survival time (for the deceased patients) in NSCLC. Furthermore, the possible mediating role of C-reactive protein (CRP) was tested (in NSCLC), as well as whether age and stage moderated the relationship between HRV and prognosis in both types of cancer. In the PC patients, HRV significantly inversely predicted PSA levels at 6 and 24 months, independent of confounders. Furthermore, this was particularly significant in metastatic PC patients, indicating moderation by stage. In NSCLC patients, HRV did not predict OS and survival time, but it did positively predict survival time in patients under the age of 65, independent of confounders. Additionally, CRP was not found to mediate the relationship between HRV and OS or survival time in NSCLC. The present results partly support previous studies and extend them to two additional common types of cancer, using a more rigorous control over confounders. Together with recent experimental findings, these results propose a modulatory role of vagal nerve activity in cancer. Therefore, routine measurement of HRV in estimating prognosis in cancer may be considered.

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Does the vagus nerve inform the brain about preclinical tumours and modulate them?

Cited by 100 publications

References 31 publications

Neural control of the anorexia-cachexia syndrome

Neural control of the anorexia-cachexia syndrome

Influence of Cancer Severity and Functional Status of Cancer on Cardiac Parasympathetic Indicators

The relationship between vagal nerve activity and clinical outcomes in prostate and non-small cell lung cancer patients

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