Tachykinin Peptide, Substance P, and Its Receptor NK-1R Play an Important Role in Alimentary Tract Mucosal Inflammation During Cytotoxic Therapy

Abstract

The alimentary tract mucosal inflammation has been a topic of concern in oncology; though many modalities of treatment have been proposed for mucosal inflammation, the contributing adverse effects have severely affected the quality of life of patients. This review focuses on the importance of neurogenic peptide, Substance P and its receptor NK-1R in modulating the cascades of events in mucosal inflammation during cytotoxic therapy. There are various preclinical and clinical models showing increased expression of Substance P/NK-1R in ionizing radiation and chemotherapy, but only very few preclinical studies to our knowledge have highlighted or examined its role in mucosal inflammation. Hence, the importance of neuropeptide involved in the inflammatory events in mucosal inflammation in cytotoxic therapy could be a major breakthrough for future research purposes and treatment. The factors contributing to the severity of tissue reactions have been multietiogenic; thus, resultant treatment also has to be directed toward multiple contributing factors. This review also focuses on the significance of care strategy to be adopted in alimentary tract mucositis when multietiogenic factors are taken into consideration.

The role of substance P in epilepsy and seizure disorders

“…SP can influence a wide range of inflammatory diseases in respiratory, gastrointestinal, and musculoskeletal systems [ 80 ]. In the CNS, consistent with observed increases after acute seizures, SP immunoreactivity was found to be stimulated both perivascularly and in cortical neurons and astrocytes following diffuse traumatic brain injury in both animal and clinical studies [ 81 , 82 ]. Elevated SP can directly increase BBB permeability and subsequent plasma protein extravasation [ 81 ].…”

A new alimentary tract mucosal inflammation model and a possibility of receptor targeted therapy in tissue reactions in cytotoxic therapy

“…There are various treatment modalities available for the mucosal inflammation in cytotoxic therapy, but most of them are limited to symptomatic treatment, and none of the treatment modalities have shown complete beneficial to the patients. With regard to the mucosal inflammation in preclinical models, the role of the neuropeptides has shown positive results [1,2]. The mucosal inflammation is a result of an initiating, modulating, promoting and activating factor; these factors then could comprehend the mitigating strand responsible for the aggressive nature of mucosal inflammation.…”

“…mucosal inflammation are less often studied; taking examples from preclinical and clinical observations, we have proposed and suggested the importance of neuropeptides in mucosal inflammation and tissue reactions in cytotoxic therapy [1,2]. Cytotoxic therapy remains an initiating factor in oral mucosal inflammation; whereas psychosocial factors, stress, biological factors and the local factors could modulate, promote and activate the mucosal inflammation ( Fig.…”

“…Cytotoxic therapy remains an initiating factor in oral mucosal inflammation; whereas psychosocial factors, stress, biological factors and the local factors could modulate, promote and activate the mucosal inflammation ( Fig. 1) [1,2]. The model explains how the preclinical models could be adapted to the mucositis clinical studies emulating on the neuropeptide, Substance P (SP) and its receptor, NK-1R expression on the alimentary tract mucosa, larynx, irradiated salivary gland, etc.…”

“…The model explains how the preclinical models could be adapted to the mucositis clinical studies emulating on the neuropeptide, Substance P (SP) and its receptor, NK-1R expression on the alimentary tract mucosa, larynx, irradiated salivary gland, etc. [1,2]. In the alimentary tract inflammation model in cytotoxic therapy shows the expression of inflammatory cytokines, TNF-a, IL-1b and IL-6, through the up-regulation of transcription factor NF-jB [3][4][5].…”