Visceral Neurophysiology Laboratory

Pain processing from internal organs  - Pain is an essential component of life. It is a protective sensation that informs us to avoid harmful situations and tissue damage. Noxious stimuli are vital to tell us when a particular movement or task is putting too much strain (or potential damage) on our bodies. Nociceptors are sensory receptors whose transduction sites respond to potentially damaging (painful) stimuli by sending action potentials to the spinal cord and brain. This process is referred to as nociception. Our laboratory uses genetically modified mice to determine how pain is detected from within internal organs and transmitted to the central nervous system.

The Enteric Nervous System - The gut wall contains a complete network of intrinsic nerves capable of propelling contents along the bowel, without any influence from nerves in the brain or spinal cord. Work in our laboratory aims to understand how intrinsic nerves in the gut wall are activated to cause the contents within the bowel to be propelled from one region to another. Our current research projects broadly address two fundamental areas of interest; (1) mechanisms of activation of spinal afferent pain pathways following colo-rectal distension, and in response to intestinal inflammation, and (2) the intrinsic neuronal mechanisms underlying colonic propulsion.
Our broad underlying goal is to determine the mechanisms of activation of intrinsic neural networks underlying complex propulsive motor patterns in the large intestine, eg. the migrating motor complex, and how these neural networks become dysfunctional in a variety of complex disease states. We use a variety of novel techniques, including in vivo and in vitro imaging of intracellular calcium, video imaging and spatio-temporal mapping of the colonic wall movements.
Dr Vladimir Zagorodnyuk joined our laboratory in 2008 and works with us on visceral pain pathways from the urinary bladder and rectum to the spinal cord. In 2009, our laboratory was awarded two independent external research grants by the National Health & Medical Research Council of Australia (NHMRC) to directly investigate; (1) visceral pain pathways following rectal stimulation and (2) the mechanisms underlying impaired colonic transit in response to chronic constipation.

Investigators

Nick Spencer, PhD
Vladimir Zagorodnyuk, PhD
David Wattchow, MBBS, PhD, FRACS
Marcello Costa, MD, FAA
Phillip Dinning, PhD

Visiting Research Fellows / Scholars

John Arkwright, PhD, CSIRO, Sydney

Support staff

Melinda Kyloh, Technical Assistant
Sarah Nicholas, Technical Assistant

Students

Simona Carbone, BSc(Hons), PhD Student (co-supervised with Simon Brookes)
Tim Hibberd, BSc(Hons), PhD Student (co-supervised with Simon Brookes)
Gretta David, BSc(Hons), PhD Student
Tiong Chen Sia, MBBS, PhD Student
Angela Chau, BMSc Placement Student

Contacts

Dr Nicholas Spencer
Ph: (08) 8204 4241 Int Ph: +61 8 8204 4241 Fax: (08) 8204 5768 Int Fax: +61 8 8204 5768 Email: nicholas.spencer@flinders.edu.au University Profile Page

Research Projects

• Mechanisms underlying the detection of pain in the gut
• Calcium imaging of human colonic smooth muscle
• Sensory innervation of the bladder

Collaborative Research

Prof Simon Brookes, Flinders University: Identification of the nerve endings that detect and signal painful stimuli to the brain. Prof Brookes' laboratory has pioneered an anterograde neuronal labelling technique, which allows identification of the nerve endings that detect painful stimuli.

Dr Grant Hennig, University of Nevada: Calcium imaging of intestinal wall movements in living mice.

Dr Michael Jackson, Department of Immunology, Allergy & Arthritis, Flinders University: Effects of autoantibodies on colonic motility.

Dr John Arkwright (Division of Materials Science and Engineering, CSIRO) and Dr Philip Dinning (Human Physiology, Flinders University): Fibre optic technology for simultaneous recordings of intraluminal wall tension/pressure from 120 sensors/sites within the isolated full length human colon. We have made the first fibre optic recordings of intraluminal colonic wall tension from the isolated intact full length human colon.

Selected Recent Publications

Arkwright J, Blenman NG, Underhill ID, Maunder SA, Spencer NJ, Costa M, Brookes SJ, Szczesniak M & Dinning P (In press) A fibre optic catheter for simultaneous measurement of longitudinal and circumferential muscular activity in the gastrointestinal tract. Journal of Biophotonics

Arkwright J, Blenman NG, Underhill ID, Maunder SA, Spencer NJ, Costa M, Brookes SJ, Szczesniak M & Dinning P (In press) Measurement of muscular activity associated with peristalsis in the human gut using fibre Bragg grating arrays. IEEE- Sensors

Zagorodnyuk VP, Kyloh M, Nicholas S, Peiris H,  Brookes SJ, Chen BN & Spencer NJ (2011) Sensory mechanisms underlying selective loss of visceral pain from the murine aganglionic colorectum. Journal of Physiology, 589: 1691-706

Spencer NJ, Hennig GW, Jokela-willis S, Lee H-T, Bayguinov PO, Ritchie LA, Ward SM, Smith TK & Sanders KM (2010) ICC-MY coordinate smooth muscle contractions in the murine small intestine. Neurogastroenterology & Motility, 22:138-151

Kyloh M, Nicholas S, Zagorodnyuk VP, Brookes SJ & Spencer NJ (2010) Identification of the pain pathway activated by noxious rectal distension in mice. Frontiers in Enteric Neuroscience, 22:5,16

Gregory S & Spencer NJ (2010) Peristalsis and fecal pellet propulsion do not require nicotinic, purinergic,  5-HT and NK3 receptors in guinea-pig distal colon. American Journal of Physiology, 298(6):G952-61

Keating DJ & Spencer NJ (2010) Release of 5-Hydroxytryptamine From the Mucosa Is Not Required for the Generation or Propagation of Colonic Migrating Motor Complexes. Gastroenterology, 138(2), 659-670

Zagorodnyuk VP, Brookes SJ & Spencer NJ (2010) Structure-function relationship of sensory endings in the gut and bladder. Autonomic Neuroscience-Basic and Clinical, 153(1): 3-11

Dinning PG, Arkwright JW, Costa M, Wiklendt L, Hennig GW, Brookes SJ & Spencer NJ (2010) Temporal relationship between intestinal patterns of motor activity and high resolution intraluminal manometry in the isolated rabbit small intestine. American Journal of Physiology, 300:G577-85

Zagorodnyuk VP, Brookes SJ, Spencer NJ & Gregory S (2009) Mechanotransduction and chemosensitivity of two major classes of bladder afferents with endings in the vicinity to the urothelium. Journal of Physiology 587: 3523-38

Jackson MJ, Spencer NJ, Reed JH, Smith AJF & Gordon TP (2009) Potentiation of a functional autoantibody in narcolepsy by a cholinesterase inhibitor. Laboratory Investigation 89: 1332-9

Dickson E, Hennig GW, Lee HT, Spencer NJ & Smith TK (2008) Colonic elongation activates polarized neural reflexes in guinea-pig colon. Journal of Physiology 586: 4225-40

Spencer NJ, Kerrin A, Hennig GW & McDonnell O (2008) Identification of capsaicin-sensitive rectal mechanoreceptors activated by rectal distension in mice. Neuroscience 153: 518-534

Spencer NJ, Kerrin A, Zagorodnyuk VP, Hennig GW, Brookes SJ, McDonnell O (2008) Identification of functional intramuscular rectal mechanoreceptors in aganglionic rectal smooth muscle from piebald lethal mice. American Journal of Physiology 294: G855-867

Spencer NJ, Hennig GW, Bayguinov P, Park K-J, Lee H-T, Heredia D, Sanders KM & Smith TK (2007) Activation of neuronal circuitry and Ca2+ waves in longitudinal and circular muscle during colonic MMCs and the consequences of rectal aganglionosis in mice. American Journal of Physiology 292(2):G546-555

Spencer NJ, Dickson EJ, Hennig GW, Bayguinov P, Heredia D & Smith TK (2007) An intrinsic occult reflex underlies accommodation of the large bowel. Gastroenterology 132(5):1912-24

Lee H-T, Hennig GW, Fleming NW , Keef KD, Spencer NJ, Ward SM, Sanders KM & Smith TK (2007) Mechanisms and spread of pacemaker activity through interstitial cells of Cajal in human jejunum. Gastroenterology 132(5):1852-65

Lee H-T, Hennig GW, Fleming NW , Keef KD, Spencer NJ, Ward SM, Sanders KM & Smith TK (2007) Septal interstitial cells of Cajal conduct pacemaker activity to excite muscle bundles in human jejunum. Gastroenterology 133(3):907-17

Updated November 2, 2011