Role of sensory neurons in restitution and healing of gastric ulcers.
It has been shown that capsaicin-sensitive afferent fibers play a crucial role in acute gastroprotection. Release of neurotransmitters such as calcitonin gene-related peptide (CGRP) and the consequent increase in mucosal blood flow have been identified as key factors in the protective effect of the stimulation of these fibers by capsaicin. Conversely the involvement of sensory nerves in the process of tissue repair after acute and chronic gastric mucosal damage has remained largely unexplored. Some studies, however, while demonstrating that the process of rapid repair (restitution) of the gastric mucosa damaged by ethanol is unaffected by capsaicin pretreatment, have shown that the recovery of gastric integrity after mucosal damage induced by sodium taurocholate or monochloramine, a known cytotoxic agent present in H. pylori patients, requires an intact sensory function and the maintenance of an adequate blood supply. In addition, a delayed healing (up to 1 week) of HCl-induced gastric lesions has been reported in capsaicin-deafferented rats, in association with a selective impairment of the hyperemic response to acid. Healing of gastric lesions induced by indomethacin, ischaemia and reperfusion, water restraint stress or concentrated ethanol was delayed in animals with functional ablation of sensory nerves. In a well-validated model, such as chronic gastric ulcers induced in rats by subserosal injection of acetic acid whose lesions last up to 4 weeks, the chemical ablation of sensory neurons negatively interferes with the process of chronic ulcer healing. The delay in ulcer healing was found to be associated with a persistent decrease in tissue levels of gastric CGRP and with a change of inflammatory mediators and growth factors, while gastric secretion and emptying were not concomitantly affected. Taken together, these data suggest that capsaicin-sensitive afferent nerves may play a role in the process of ulcer healing by mediating the hyperemic response through the release of CGRP and facilitating the acid disposal in the mucosa. From a therapeutic perspective, it is obvious that the compound acting on this system could have a role in the healing processes of the stomach damage.
Evangelista
S
S
Preclinical Development Dept., Menarini Ricerche SpA, Via Sette Santi 1, 50131 Firenze, Italy. sevangelista@menarini-ricerche.it
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology / Q000627:therapeutic use; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D006801:Humans; D009475:Neurons, Afferent / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000503:physiopathology
D002211:Capsaicin