# The Role of Lumbar Splanchnic Innervations in Visceral Nociception and Pain

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT STORRS · 2020 · $397,176

## Abstract

Project Summary/Abstract
 Chronic visceral pain is the cardinal symptom of patients with irritable bowel syndrome (IBS) affecting up to
15% of the U.S. population. Efficacious and reliable therapeutic intervention is still unavailable despite the
tremendous economic burden imposed by visceral pain. Drugs to treat visceral pain impact both the peripheral
and central nervous systems (PNS, CNS) due to similar ion channel/modulator composition, and CNS-related
side effects usually outweigh analgesic benefits. Visceral pain differs significantly from other types of pain in the
`adequacy' of nociceptive stimuli, defined first by Sherrington as triggering painful and noxious reactions. Noxious
cutaneous stimuli (e.g., cutting, pinching, burning) are not reliably nociceptive when applied to hollow visceral
organs, whereas mechanical visceral organ distension (stretch/tension) is `adequately' nociceptive. In addition
to previous studies that reveal the role of pelvic nerve (PN) afferents in encoding colorectal distension and
contributing to prolonged colorectal hypersensitivity, we reveal, for the first time, a more significant participation
of afferents in the lumbar splanchnic nerves (LSN) in encoding colorectal distension than previously assumed:
~40% of LSN afferents encode axial colorectal stretch, which is also produced by colorectal distension. We also
found that: 1) the colorectal region with dense LSN innervation (next to the mesentery) is more compliant
mechanically than the adjacent region, and 2) the colorectal submucosa has a rich network of load-bearing
collagen fibers. Our new neural and mechanical data suggest an underappreciated role for LSN afferents in
encoding colorectal distension, an `adequate,' noxious stimulus that evokes visceral pain in IBS patients.
 Accordingly, the objective of this proposal is to reveal lumbar splanchnic afferent neural encoding of
colorectal distension and nociception at macro- and micro-mechanical, and molecular levels. Three specific aims
are proposed. Aim 1 will quantify lumbar splanchnic afferent neural encoding of colorectal distension and
colorectal nociception in prolonged colorectal hypersensitivity. Aim 2 will quantify macro- and micro-mechanics
of differential mechanical neural encoding of colorectal afferent endings in the lumbar splanchnic pathway. Aim
3 will define the molecular profiles relevant to colorectal mechanosensitivity of different lumbar splanchnic
afferent classes in prolonged colorectal hypersensitivity. The proposed study of the biomechanical factors in
colorectal mechanosensitivity and hypersensitivity will complement existing neurophysiological approaches to
synergistically advance our mechanistic understanding of colorectal afferent neural encoding and nociception,
especially in the lumbar splanchnic pathway. Through this proposed research, we will establish the influence of
biomechanics in colorectal mechanosensitivity and nociception in prolonged colorectal hypersensitivity. T...

## Key facts

- **NIH application ID:** 9994983
- **Project number:** 5R01DK120824-02
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** Bin Feng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $397,176
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994983

## Citation

> US National Institutes of Health, RePORTER application 9994983, The Role of Lumbar Splanchnic Innervations in Visceral Nociception and Pain (5R01DK120824-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9994983. Licensed CC0.

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