Mechanosensitive Properties of Gastric Vagal Afferent Fibers in the Rat

Abstract

Single, teased fiber recordings were made from the decentralized right cervical vagus nerve (hyponodal) of the rat. A total of 67 afferent fibers that responded to gastric distension (GD) were studied: 9 fibers were stimulated by phasic balloon GD, 58 by more natural fluid GD. All balloon GD-responsive fibers had resting activity (3.1 imp/s), and 57/58 fluid GD responsive fibers had resting activity (1.3 imp/s). All balloon GD-responsive fibers exhibited a dynamic response to phasic distension followed by slow adaptation, whereas fluid GD-responsive fibers exhibited increasing responses as intragastric pressure increased, followed typically by slow adaptation. Responses to graded GD were studied in all fibers, and all gave increasing responses to increasing pressures (5-60 mmHg). Thresholds for response varied between 0 and 18 mmHg. Mean response thresholds for two durations of fluid GD (30 and 60 s) were 5.6 and 3.9 mmHg; the mean response threshold to phasic balloon GD (30 s duration) was 5.3 mmHg. The potential sensitizing effect of platelet activating factor (PAF, 50 or 100 ng. kg(-1). min(-1) for 20 min) infused into the gastric artery was studied in 20 fibers. Fifteen fibers exhibited an increase in spontaneous activity; intragastric pressure also slightly increased during PAF infusion. The increase in activity produced by PAF was attenuated in the presence of the PAF receptor antagonist WEB 2086. After PAF-induced acute inflammation of the stomach, three of five fibers studied did not exhibit any change in response to graded GD. The present study characterized distension-sensitive afferent fibers in the right cervical vagus innervating the stomach of the rat by balloon GD and fluid GD. The results document that all distension-sensitive gastric vagal afferent fibers encoded the intensity of GD, but none had response thresholds in what might be considered the noxious range. PAF infusion activated mechanosensitive gastric vagal afferent fibers, but acute inflammation produced by PAF did not sensitize responses to GD.

Dichotomizing Axons in Spinal and Vagal Afferents of the Mouse Stomach

“…Thus, considering the discrepancy between the known fraction of highthreshold mechanosensitive fibers and the predominant labeling of spinal visceral afferent neurons by either TRPV1 or CGRP antibodies, these neurochemical markers do not identify nociceptive neurons. This is further supported by the presence of TRPV1 immunoreactivity in about 40% of nodose neurons innervating the stomach, as no high threshold and thus presumably nociceptive mechanosensitive fibers have been identified in the vagal afferents innervating the stomach [6,7,32,46]. As already indicated above, our findings are in line with results obtained by other investigators studying the innervation of different viscera in various species.…”

“…Behavioral and physiological studies have demonstrated significant differences between spinal and vagal afferents innervating the proximal gastrointestinal tract [6,9,[25][26][27]. Using retrograde labels and immunohistochemistry, we characterized the afferent innervation of the mouse stomach and duodenum.…”

“…Essentially, all mechanosensitive vagal afferents are activated by lowintensity stimuli [5][6][7]. In contrast, spinal afferents can be differentiated into low-and high-threshold fibers, with about 20% of the spinal afferents requiring distension pressures exceeding 20 mmHg [8,9].…”

The effect of spinal cord injury on vagal afferents.

“…In the gastrointestinal tract, vagal afferent fibers are responsive to stretch and tension as well as to locally released hormones following the ingestion of food (Berthoud and Powley, 1992, Wang et al, 1997, Phillips and Powley, 2000, Berthoud et al, 2001). Although they are typically not responders to visceral stimuli within the noxious range (Ozaki et al, 1999), previous data from our lab and that of others suggest otherwise. For example, while spinal afferents may be responsible for relaying mechanical nociceptive information, vagal afferents may play more of a predominant role in conveying chemical nociceptive stimuli, thus contributing to disease-related conditions stemming from visceral hyperalgesia (Schuligoi et al, 1998, Michl et al, 2001, Page et al, 2002, Holzer, 2003, Sugiura et al, 2005, Kaddumi and Hubscher, 2007.…”

“…Although it is commonly thought that vagal afferents are not involved in the sensation of pain (Cervero, 1994, Ozaki et al, 1999, there is accumulating evidence that they partake in this process. For instance, gastric distention in the noxious range has been shown to result in a greater level of c-fos immunoreactivity (a marker of central neuronal activity following a peripheral stimulus) in the solitary nucleus compared to regions in the thoracic spinal cord that receive gastric input (Traub et al, 1996).…”