The pain game: AIBN researchers exploring how to better relieve chronic conditions

21 January 2025

            

Our body’s complement system is aptly named, given the supporting role it plays in fighting disease and healing injuries. 

But researchers like Marina Vygonskaya believe this network of defensive proteins might also help us address pain itself, and reduce patient reliance on opioid-based drugs.     

AIBN PhD student Marina Vygonskaya
AIBN PhD student Marina Vygonskaya is examining how the complement system can help address pain and reduce patient reliance on opioid-based drugs.

In The Journal of Pain, Marina and UQ colleagues Dr Felicity Han, Youzhi Wu, and Zhuo Chen at the Australian Institute for Bioengineering and Nanotechnology (AIBN) examine how new analgesic pharmacotherapies could be used to inhibit certain plasma proteins in the complement system that are most strongly and consistently associated with pain.  

According to the team, successfully targeting the C5 and C3a components could reduce the need for medicines like morphine to manage chronic pain, a move that could shorten treatment duration and mitigate other side effects for patients. 

“Of the available options for chronic pain treatment, opioids still remain the most used for relief despite their well-known side effects, diminishing efficacy over time, and poor outcomes,” Marina says.  

“But evidence continues to support the active involvement of our complement pathways in mediating and modulating the development of various pain types and pain persistence.” 

So what is this complement pathway?  

How can it be used to give us a better handle on pain?  

And how did a neurologist from Russia end up focusing on this subject at the AIBN?  

A misunderstood field    

Pain causes more clinical and economic burdens than just about any other health problem.  

In 2018 Deloitte found that more than 3.2 million Australians were living with some form of chronic pain at an annual cost of $139.3 billion to the economy through health costs, productivity loss, and a reduction in quality of life.  

These costs were expected to hit $215.6 billion by 2050.    

Despite this, Marina says the mechanisms underlying chronic pain and its development remain unclear, while interacting factors across biology, psychology, sociology, behaviour and the environment make any fix incredibly challenging.  

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“Pain does not seem to get the attention that other areas of health do,” Marina says.  

“So, not surprisingly, current treatments are moderately effective at best and generally have poor long-term effects.  

Marina herself says pain has been a focus throughout her career.  

Back in her native Russia, Marina was a qualified neurologist with a focus on chronic pain.   

“I’ve always had a focus on pain, but I really wanted to combine the research and medical field and get a better understanding of pain,” Marina says  

“I wanted to understand pain better in terms of physiology and anatomy, molecular targets that can help me better match patients with the right drugs and treatment.  

“I want to be able to explain better why you can't just treat pain with drugs on their own, and why you need a program with pain education, physiotherapy, psychologist or behavioural treatment.  

“It is this combination of factors that, in chronic cases, demonstrate why the problem cannot be fixed with a 15-minute appointment.”  

Moving to Australia and switching to research, Marina eventually came across Dr Felicity Han, whose work as an AIBN research fellow whose work incorporates nanotechnology into chronic pain management. 

Zhou Chen, Marina Vygonskaya, Youzhi Wu and Dr Felicity Han, published a paper in Journal of Pain
Zhuo Chen, Marina Vygonskaya, Youzhi Wu and Dr Felicity Han, published a paper in Journal of Pain

And so Marina took up a PhD at the AIBN under Dr Han’s guidance.  

The group’s paper in The Journal of Pain is an exploration of potential opioid-free treatment methods targeting the complement pathway and specific “components” within.  

A complement to the cause 

The complement system is a network of more than 30 proteins in our immune systems that help us heal after an injury or infection, and protect us from disease.  

In The Journal of Pain, Marina and her team cite evidence that supports the active involvement of complement pathways in mediating and modulating the development of various pain types and pain persistence.  

Critically, the team highlights data that shows the inhibition of specific complement system components can ameliorate or even prevent pain and various pain conditions.  

This is achieved with a promising range of drugs known as complement inhibitors.  

“While these treatments do carry the potential to slightly weaken protection against infections, the benefits on the other hand could be significant,” Marina says.  

“This includes stopping excessive neuroinflammation and chronic pain development.”  

Of the 30 or so different drug candidates either under development or being tested in clinical trials, most are designed to target the C5 pathway, C3 pathway, or C1 pathway within the complement system.  

The paper points to current preclinical data that suggests a role for C5a inhibitor administration pre- or post- surgery to reduce post-operative pain, as a preventive treatment for attenuating the development of chemotherapy-induced peripheral neuropathy (CIPN), as a novel analgesic for relief of various other chronic pain conditions, and possibly to arrest the transition of acute to chronic pain. 

Marina says the crucial next steps will be for researchers to better understand: 

  • The role of C5a and C3a components in the pathophysiology of various pain states and the transition to chronicity in humans,  

  • The mode of action, optimal dosing, optimal timing of the inhibition of signalling by C5a and C3a via their cognate receptors, and 

  • The safety (eg. abuse potential) of promising C5a and C3a inhibitors before they can be considered as potentially novel analgesics for clinical development  

“This understanding is needed to guide the development of C5 and C3 inhibitors with suitable pharmacokinetic and safety profiles and that are optimized for the pain type and stage,” Marina says.  

You can read The Journal of Pain review article for yourself here.  

Marina and her AIBN was assisted by colleagues from UQ’s School of Biomedical Sciences, as well as the NHMRC Centre of Clinical Research Excellence in Spinal Pain, Injury, and Health, and the University of Texas.  

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