A drug called dimethyl fumarate, currently used to treat the skin disease psoriasis and the autoimmune illness multiple sclerosis, is now showing promise in combating chronic pain, following Centre for Nanoscale BioPhotonics (CNBP) investigations.
The lead researcher on the project is Dr Peter Grace, an assistant professor at the MD Anderson Cancer Centre in the US, where he runs a lab investigating the neuroinflammatory mechanisms behind chronic pain. He decided to explore dimethyl fumarate’s pain relief potential because it activates a particular antioxidant defence pathway in the body that reduces oxidative stress.
‘Oxidative stress is known to drive pain signalling throughout the body,’ Dr Grace explains. ‘So, we figured if we control that, we could control pain.’
So far, animal studies have shown dimethyl fumarate is effective in reversing neuropathic pain, which is often associated with chronic lower back ache and the condition known as sciatica. Dr Grace’s research with the CNBP is now heading in two directions; one aims to improve the structure of dimethyl fumarate to remove some side effects it causes, while retaining its pain-killing capacity. The other is to explore the antioxidant defence pathway further and investigate other drugs that might also be used to target it.
Another promising option for neuropathic pain is a naturally occurring compound called zerumbone. Dr Enoch Perimal, an associate professor in the Neuroimmunopharmacology laboratory headed by CNBP Director Prof Mark Hutchinson, is investigating this currently. Zerumbone is found in high concentrations in the roots of a particular type of ginger known to have been used in the treatment of ailments throughout South-East Asia for centuries. In animal studies, Dr Perimal has shown that zerumbone is effective in reducing neuropathic pain and he’s also identified the molecular mechanisms by which it does that.
‘We know the receptors it is targeting and some of the pathways that it is interacting with in inhibiting neuropathic pain,’ Dr Perimal says. In fact, tests have shown that zerumbone acts on the same opioid receptor signalling pathway as morphine, but without the often debilitating sedative side effects. Now, Dr Perimal’s team is looking at developing a cream containing zerumbone that could be applied topically.
When developing any new treatment, it is essential to demonstrate that the target has been hit. For the treatment of cancer, you can measure the tumour size; for treating cardiovascular disease you can measure blood pressure and heart rate. But for chronic pain there is currently no objective measure of treatment success.
This creates two fundamental issues that make it difficult to treat chronic pain conditions such as rheumatoid arthritis, an autoimmune disease that can cause debilitating pain in the joints. To begin with, diagnosis is uncomfortable, time-consuming and invasive for patients, requiring synovial fluid to be removed from a patient’s knee for testing. But perhaps even more importantly, measuring pain associated with the disease is highly subjective, depending on the experiences of both the patient and their healthcare practitioner.
‘It’s reliant on the individual’s experience of pain and the practitioner actually validating what the person is feeling,’ says Florence Lees, a PhD researcher in Prof Hutchinson’s laboratory, who hopes a project she is working on can resolve the issue while finding a less invasive diagnostic test for the disease.
And researchers think they may have found the answer. Using a light technology known as hyperspectral imaging to explore and compare the molecular features of blood cells and synovial tissue of arthritis sufferers, a clinical trial led by CNBP researchers has compiled fingerprint-like ‘pictures’ of pain associated with the disease. The team is now looking to develop a simple test that could be carried out in a GP’s office, to produce similar images that will not only show the presence of disease but also the level of pain being felt by the patient, Lees explains.