Ivanusic laboratory: Pain and sensory mechanisms

Research Overview

Our ability to sense and react to our environment is governed by activity in sensory neurons. Small diameter peripheral sensory neurons can detect tissue damage (generating pain), local changes in temperature and mechanical stimuli. A more complete understanding of the mechanisms by which these stimuli generate nerve impulses in peripheral sensory neurons, and how these are altered in conditions (such as inflammation) that heighten pain, thermal and mechanical sensitivity, will allow us to better define ways in which we can treat pain.

NEURAL MECHANISMS OF BONE PAIN

We have shown that the periosteal, medullary and trabecular compartments of bone are all innervated by sensory neurons that are responsive to noxious chemical, mechanical and/or inflammatory stimuli, and have neurochemical phenotypes consistent with a role in nociception. We have been the first to document activity in the central nervous system related to stimulation of nerves in bone, and have developed animal models of inflammatory bone and joint pain that have been used to test whether peripheral application of specific drugs may be of use in the treatment of inflammatory pain. We are also currently using a newly developed whole animal bone-nerve preparation to study the physiology of bone marrow nociceptors and assay their response to potential therapeutics.

Figure 1: Immuno-labelling of sensory neurons that innervate bone

Figure 2: Behavioural testing using weight distribution as a surrogate marker for pain

Figure 3: Schematic representation of the in vivo bone-nerve preparation and representative electrophysiological recordings

STRUCTURE/FUNCTION RELATIONSHIPS IN SENSORY NERVE TERMINALS OF THE CORNEA

We are the only group in Australia (and amongst a small number worldwide) that is able to record directly from single small diameter sensory nerve terminals. We use this technique to record electrical activity from single pain and cold-sensing nerve terminals in the guinea pig cornea and then, after marking the recording site, use immunohistochemistry and high resolution microscopy to determine the structure and neurochemical profile of the nerve terminals we recorded from. We have shown that functionally defined nerve terminals in the cornea can be distinguished on the basis of their morphology and neurochemistry. Our aim is to further explore how the morphology and neurochemistry of sensory nerve terminals influences their function in both health and disease (Collaborator: James Brock, University of Melbourne).

Figure 4: Morphological and molecular phenotyping of physiologically identified corneal sensory neurons and their nerve terminal endings

PAIN MANAGEMENT USING ULTRASOUND-GUIDED PERIPHERAL ANAESTHESIA

We have established a model in which we simulate ultrasound guided nerve blocks by injecting dye into human cadaveric material under ultrasound guidance, and then explore the extent of dye spread and nerve involvement, to provide an evidence base for the use of these nerve blocks in the clinical setting. We have published explorations of sciatic nerve, transversus abdominis plane, subcostal, thoracic paravertebral and fascia iliaca block, and most of these studies have directly informed clinical practice in anaesthesia. (Collaborator: Michael Barrington, St. Vincent’s Hospital, Melbourne)

Figure 5: Ultrasound guided paravertebral block

Staff

Jenny Thai, Research assistant
Sara Nencini, PhD student
Abdulhakeem Alamri, PhD student
Amanda Wong, Honours student
Sebastian Gronert, Honours student

Collaborators

Associate Professor James Brock
Associate Professor Michael Barrington
Associate Professor Stuart Mazzone
Dr Alice McGovern