Understanding pain pathways

The mysterious language of pain and the fight to switch it off

Within our bodies, we have an intricate network of nerve cells that help us to perceive the world. They’re called sensory neurons. Sensory neurons convert external stimuli from the environment into messages within the body. One of their roles is to transmit pain messages to the brain. It is a useful process that protects us from damage (in the case of touching a hot surface), but with certain diseases, it can cause debilitating chronic pain that science is currently at a loss to treat.

Dr Irina Vetter is demystifying the different pathways that contribute to pain in various disease states so that we can help the one in five Australians that live with chronic pain.

“Chronic pain costs the Australian economy around $40 billion per year. It causes enormous disruption to people's physical and mental wellbeing and their personal life.

"There is also a lot of stigma around pain because of the lack of understanding about its cause, and because you cannot see pain," said Dr Vetter.

"And current drugs either don't work or have terrible side effects, like addiction."

Research overview

Dr Vetter is looking to change that. Through biomedical research and pharmacology, she hopes to develop better treatments for pain - targeted treatments with no adverse side effects. She is searching for the answer to pain in what might seem like a peculiar place – venoms.

“Sensory neurons transmit pain messages, and for a sting to be effective, it must be painful. So venomous animals and toxins have evolved to very specifically target sensory neurons. To treat pain, we also need to be able to target sensory neurons, so we’re examining the active components in venom and toxins to see if they can teach us how to do that.”

Dr Vetter’s research group is currently very excited by a venom-derived compound that targets a particular protein on a nerve whose role is to signal pain.

“The protein is not involved in touch or other sensations. So this compound has exciting prospects as a pain drug.  It is very selective, which means it doesn’t have any side effects, so we will take this further and hopefully make a new drug,” said Dr Vetter.

The group is confident that the drug will be effective against common types of acute pain and a rare and excruciating disease called Man on Fire Syndrome. But they are hopeful that it will be useful in a treating a wide variety of disease-related pain.

The group is currently looking for funding to continue their research on the compound.

The translation of this research into a usable drug is a long process. But the Vetter Group is also employing unique pharmacological methods to repurpose existing drugs, for more immediate translations into clinical practice.

The Vetter Group spread themselves right across cell-based studies to tests on living organisms.

"IMB is quite marvellous in the sheer knowledge and capability in one building. Whatever your problem, there will be an expert in the building, so there is little that we can't achieve. The diversity of the researchers, the techniques used, and the facilities are second to none.”

"We have a translational capability. We always make sure that what we find in a cell has meaning in an organism. We're well placed to deliver real outcomes."

Dr Vetter has always been fascinated by how we perceive the world around us, in particular, the role of sensory neurons in the body.

“They sit alongside our spinal cord and shoot out these projections that can be up to a meter long, reaching out to our fingers and our toes, and they tell us about the environment around us. And they’re a mystery. There is a lack of fundamental knowledge about how they work.

“Not every type of pain is the same. The mechanisms that lead to pain in cancer and diabetes, for example, can be entirely different. We are interested in understating exactly how chronic pain arises in each disease state so that we can treat it accordingly.”

“I have always had an interest in developing drugs, I studied and practiced as a pharmacist. I love that we can directly translate what we do in the lab to something that you feel.” 

Research projects

Pain is a major medical and socio-economic issue affecting one in five Australians. Our research aims to understand the molecular mechanisms behind pain. The current focus of the lab is to use toxins from plants and venomous animals to understand the molecular pharmacology of pain. These toxins are highly selective for ion channels and receptors found in the sensory neurons that detect pain and can potentially be developed into novel analgesics.

Our research also investigates the mechanisms contributing to chemotherapy-induced pain, cancer-associated pain, inflammatory and neuropathic pain, and the painful marine toxin disease known as ciguatera.

To investigate the neuropharmacology of pain we use a range of techniques including: in vivo pain pathway characterisation, high-content imaging of cultured sensory neurons, high-throughput screening using calcium and membrane potential assays, and traditional pharmacological assays. While all pain has similar symptoms, it is becoming clear that the underlying mechanisms behind pain can vary.

By uncovering these new pain pathways, as well as identifying novel targets on peripheral sensory neurons, we aim to develop more effective pain therapies that treat the underlying cause of the pain, not just the symptoms.

Research training opportunities

Research title: Neuropharmacology and pain contact 

Summary of research interests: Sensory neurons are fundamental for our interaction with the external world by detecting stimuli including cold, heat, touch, pressure, vibration and tissue injury. These external stimuli are then transformed to electrical signals through specialised molecules, which detect temperature, mechanical stimulation and various chemicals. Although significant progress has been made towards determining the molecular identity of selected receptors and ion channels involved in sensory perception, our understanding of how these contribute to sensory perception, and in particular pain, is limited. Toxins from plants and animal venoms have provided highly specific tools, which allow dissection of the mechanisms of sensory perception and pain and may provide novel molecules with analgesic potential.

Traineeships, honours and PhD projects include

  • Fundamental basis of peripheral sensory perception
  • Identifying and characterising the effect of venoms and toxins on peripheral sensory neurons
  • Identifying, characterising and optimising molecules with therapeutic potential from natural sources including venoms
  • Understanding the pathophysiology of pain and optimising analgesic treatment approaches.

Contact: Dr Irina Vetter

+61 7 3346 2660
i.vetter@imb.uq.edu.au


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Engagement and impact

The research vision of the Vetter group is to bring innovation to the area of neuropharmacology of pain by combining expertise in venom peptide discovery and characterisation with our outstanding capacity in in vivo and in vitro pain pathway characterisation. This approach will provide insight into the pathophysiology of pain, a better understanding of the role of ion channels in pain, and identification of novel putative pain targets that will generate long term transformational and translation/commercialisation impact to benefit patients suffering from pain.

Using this approach, we have discovered a novel compound from spider venom that acts on pain-sensing nerves specifically. It has potential as an analgesic without side effects such as tolerance or addiction. The ultimate aim of their research is to develop targeted treatments without side effects to help the one in five Australian’s living with chronic pain.

Partners and collaborators

Dr Vetter works in collaboration with other leading Australian and international researchers to identify novel therapeutic pain pathways and targets. The Vetter group uses whole cell patch-clamp electrophysiology, automated electrophysiology, high-content and high-throughput imaging of dissociated sensory neurons as well as transiently or stably transfected mammalian cell lines to assess pharmacological effects on a range of ligand- and voltage-gated ion channels as well as G protein-coupled receptors. Her group routinely perform high-content screening and pharmacological characterisation of compounds from a range of sources and have established a state-of-the-art behavioural facility and single fiber extracellular recording setup at the University of Queensland for translational to preclinical models. 

In collaboration with leading peptide chemists, molecular biologists, electrophysiologists, clinicians, NMR and structural biology experts, the Vetter group seeks to unravel the molecular and structural basis of nociception.

Our past and present collaborators span a network of world-class researchers with complementary skill sets that further strengthen our capacity to conduct the highest quality research and produce outstanding research outcomes. Our collaborators are the best in the world in their respective fields, including mathematics, biophysics, membrane interactions, structure determination, modelling, transcriptomics, ion channel pharmacology, chemistry, pain management and ex vivo sensory recordings.
 

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Dr Irina Vetter

Dr Irina Vetter

Group Leader, Chemistry and Structural Biology Division

Deputy Director, Centre for Pain Research

  +61 7 3346 2660  
  i.vetter@imb.uq.edu.au
  IMB Researcher Profile
  Centre for Pain Research


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  Group Leader

  Researchers

  Students

  • Ms Mathilde Israel

    Higher degree by research (PhD) student
    Institute for Molecular Bioscience
  • Mr Alexander Mueller

    Mr Alexander Mueller

    Higher degree by research (PhD) student
    Institute for Molecular Bioscience
  • Ms Hana Starobova

    Higher degree by research (PhD) student
    Institute for Molecular Bioscience
  • Mr Bryan Tay

    Higher degree by research (PhD) student
    Institute for Molecular Bioscience