Differential roles of stretch-sensitive pelvic nerve afferents innervating mouse distal colon and rectum

Abstract

Feng B, Brumovsky PR, Gebhart GF. Differential roles of stretchsensitive pelvic nerve afferents innervating mouse distal colon and rectum. Am J Physiol Gastrointest Liver Physiol 298: G402-G409, 2010. First published January 14, 2010; doi:10.1152/ajpgi.00487.2009.-Information about colorectal distension (i.e., colorectal dilation by increased intraluminal pressure) is primarily encoded by stretch-sensitive colorectal afferents in the pelvic nerve (PN). Despite anatomic differences between rectum and distal colon, little is known about the functional roles of colonic vs. rectal afferents in the PN pathway or the quantitative nature of mechanosensory encoding. We utilized an in vitro mouse colorectum-PN preparation to investigate pressure-encoding characteristics of colorectal afferents. The colorectum with PN attached was dissected, opened longitudinally, and pinned flat in a Sylgard-lined chamber. Action potentials of afferent fibers evoked by circumferential stretch (servo-controlled force actuator) were recorded from the PN. Stretch-sensitive fibers were categorized into the following four groups: colonic muscular, colonic muscular/mucosal, rectal muscular, and rectal muscular/mucosal. Seventy-nine stretchsensitive PN afferents evenly distributed into the above four groups were studied. Rectal muscular afferents had significantly greater stretch-responses than the other three groups. Virtually all rectal afferents (98%) had low thresholds for response and encoded stimulus intensity into the noxious range without obvious saturation. Most colonic afferents (72%) also had low thresholds (Ͻ14 mmHg), but a significant proportion (28%) had high thresholds (Ͼ18 mmHg) for response. These high-threshold colonic afferents were sensitized to stretch by inflammatory soup; response threshold was significantly reduced (from 23 to 12 mmHg), and response magnitude significantly increased. These results suggest that the encoding of mechanosensory information differs between colonic and rectal stretch-sensitive PN afferents. Rectal afferents have a wide response range to stretch, whereas high-threshold colonic afferents likely contribute to visceral nociception. muscular afferents; muscular/mucosal afferents; single-fiber recording; irritable bowel syndrome FUNCTIONAL GASTROINTESTINAL DISORDERS such as irritable bowel syndrome (IBS) are characterized by altered bowel habits, discomfort, pain, and colorectal hypersensitivity (12). Typically, patients have significantly lower response thresholds to provocative visceral stimuli (e.g., distension of hollow organs) and complain of increased sensitivity and discomfort to ingestion of food or beverages (16). Balloon distension of the pelvic colorectum has been widely employed to quantify sensation (principally discomfort and pain) in patients with IBS as a means of assessing colorectal hypersensitivity relative to normal subjects (e.g., Ref.3). Growing evidence from both clinical and basic science research reveals that peripheral sensory input plays a key role in sustaining visceral p...

Optogenetic activation of mechanically insensitive afferents in mouse colorectum reveals chemosensitivity

“…Falloff of laser-evoked action potentials started to occur when the stimulus frequency exceeded 3 Hz, and stimulation at 10 Hz evoked significantly less repetitive firing in both MIAs and MSAs, suggesting that the spike initiation zone of colorectal afferents is not capable of high-frequency firing. This is consistent with previous findings by us and others that mouse colorectal afferents are generally low firing (Ͻ5 Hz), even when stimulated at noxious intensities (2,3,7). Consistent with unpublished observations (B. Feng and G. F. Gebhart), the peak frequency of chemically induced discharges seldom exceed 5 Hz, comparable with the range of laser-evoked peak firing frequencies in Cre ϩ/Ϫ…”

“…All MIA and MSA RFs were subsequently stimulated optically and MIAs were also tested for activation/ sensitization with inflammatory soup (IS), acidic hypertonic solution (AHS), and/or bile salts (BS). Responses to pulsed optical stimuli (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) were comparable between MSAs and MIAs whereas 43% of MIAs compared with 86% of MSAs responded tonically to stepped optical stimuli. Tonic-spiking MIAs responded preferentially to AHS (an osmotic stimulus) whereas non-tonicspiking MIAs responded to IS (an inflammatory stimulus).…”

“…MIAs that responded to optical stimulation were tested by sequential exposure of their afferent endings to an acidic hypertonic solution (AHS) and an inflammatory soup (IS), each of which has been used previously on colorectal afferent endings (7,8,12,20,21). Brass tubing of 1-cm high ϫ 4-mm square, which has been shown to be chemically inert to AHS, IS, and bile salts (BS), was placed over the receptive ending on the mucosal surface, the Krebs was solution removed, and 150 l of AHS solution were applied directly to the receptive ending for 5 min.…”

Extrinsic primary afferent signalling in the gut

“…46 First described in the 1960s, these endings are associated with branch points of mesenteric arteries and encode both contraction and distension of the gut wall and traction on the mesenteries, 79 with relatively low sensitivity. This low sensitivity is particularly marked in the noncompliant, thick-walled mouse colorectum, 80 which might have led to their distension sensitivity being missed in some studies. 46,81 Similar afferent endings have been confirmed in other regions of the gut in several species.…”

Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

“…Muscular / mucosal afferents respond to fine tactile stimuli and low intensity circular stretch, and in the colo-rectum are unique to the pelvic afferent pathway where they comprise approximately 25% of the total afferent population (Brierley et al, 2004;Feng et al, 2010;Hughes et al, 2009b). These afferent nerves respond linearly to increasing levels of distension and signal into the noxious range.…”