Sensitization of visceral afferents to bradykinin in rat jejunum in vitro

Abstract

The gastrointestinal tract has an extensive intrinsic and extrinsic sensory innervation. Despite this, stimuli in the healthy gastrointestinal tract rarely reach the level of conscious perception. In contrast, sensations of abdominal discomfort and pain are common symptoms in patients with gastrointestinal disease. Symptoms include heartburn, chest pain, dyspepsia, bloating, abdominal cramps and feelings of incomplete rectal evacuation, all of which can arise in both organic (e.g. inflammatory) and functional disorders such as irritable bowel syndrome. Visceral afferent hypersensitivity is now a widely accepted mechanism which could explain many of these clinical symptoms associated with functional bowel disease and inflammatory diseases of the gut (Mayer & Raybould, 1990;Bueno et al. 1997). However, the mechanisms underlying peripheral sensitization of gastrointestinal afferents is poorly understood. Much of our understanding of the mechanisms of afferent sensitization and the modulation of painful stimuli has stemmed from studies of cutaneous pain. Sensitization of cutaneous nociceptors is thought to underlie conditions of hyperalgesia (enhanced perception of pain) and allodynia where previously non-noxious stimuli can produce pain (Heller et al. 1993). Despite the lack of detailed studies on gastrointestinal afferent sensitivity, it is generally assumed that intestinal afferents behave in a similar way, being activated andÏor sensitized by chemical mediators present within an 'inflammatory soup'. Gastrointestinal afferents terminate at different levels within the gut wall (namely

TRPA1 in bradykinin-induced mechanical hypersensitivity of vagal C fibers in guinea pig esophagus

“…One explanation for this difference is that different animal species (such as opossum and guinea pig) may have a different population of vagal sensory afferent nerve subtypes and that the different embryonic origin of these subtypes of sensory afferents may determine their distinct functions. We also show that this repeatable activation in vagal nodose and jugular C fibers is inhibited by BK B2-receptor antagonist, which is consistent with previous studies showing that BK activated gastrointestinal sensory afferents directly through B2-receptor on the nerve endings (4,6,21,30,31). That BK increased the responses of colonic afferent fibers to probing and enhanced responsiveness of upper thoracic spinal neurons to esophageal distension indicated that BK might potentiate mechanoexcitabilities of these sensory afferents and spinal neurons (5,28).…”

“…BK not only directly activates sensory afferents but also subsequently sensitizes their responses to other stimuli, thus playing an important role in peripheral nerve sensitization (36). It has been reported that BK activates sensory afferent nerves innervating different parts of the gastrointestinal tract, including the esophagus (28,33), jejunum (6,21), and colon (5,30). An increased response to mechanical stimulation (probing) has been described in pelvic colonic afferents following the perfusion of BK (5).…”

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

“…Serotonin facilitated spike discharges evoked by bradykinin in canine testicular nociceptors, rat cutaneous nociceptors, canine perivascular afferents, and human muscular nociceptors (31, 114, 403, 502) as well as the bradykinin-induced overt nociception (293) but failed to sensitize to bradykinin visceral afferents of the rat jejunum (70). In the latter preparation, histamine or adenosine exerted a sensitizing effect to bradykinin, and these effects were mimicked by an analog of cAMP.…”

“…IID1B). Exogenously applied prostanoids (mostly PGE 2 , PGE 1 , and PGI 2 ), however, typically failed to cause neuronal spike discharges (70,96,247,287,326,403,499,501,502,616) or pain (121, 294,366,512,618).…”

Targeting Histamine Receptors in Irritable Bowel Syndrome: A Critical Appraisal

“…Additionally, histamine induced murine jejunal afferent firing and excited primary sensory neurons. 46,47 According to the study of Barbara et al, 43 the pronociceptive effect of histamine appears to be mediated, at least partly, by H 1 R expressed on sensory afferents. In contrast, Guarino et al 48 found that supernatants from patients with IBS impair contractility of isolated human colonic smooth muscles and the phenomenon is histamine-independent.…”