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Getting a genetic-eye view of pain
In a previous blog post, I highlighted the subjective, individual, and paradoxical phenomenon of pain, and how this makes diagnosing and treating pain such a challenge. For over three years, I have been working on a project led by my colleague Dr Patrick McHugh, Huddersfield University, that focuses on the ‘Holy Grail’ of pain research; finding a biomarker (i.e., a biological characteristic) for the subjective phenomenon of pain. This week saw the publication of our study ‘The Identification of Blood Biomarkers of Chronic Neuropathic Pain by Comparative Transcriptomics’ that makes a step towards this goal.
Chronic neuropathic pain
Our study focussed on one type of pain, called chronic neuropathic pain. Chronic neuropathic pain is a harmful condition that results from disease or damage of nerves in the brain, spinal cord, and the periphery. Typical symptoms are severe and unrelenting tingling, shooting, or burning pain, that may ‘come and go’, leaving the person anxious and fearful of the next painful attack. Paradoxically, chronic neuropathic pain may be accompanied by numbness for some people, or extreme touch sensitivity for others.
Causes of chronic neuropathic pain include nerve compression, amputation, stroke, multiple sclerosis, viral infection, diabetes, and treatments such as chemotherapy. Drugs used for symptomatic relief include anti-depressants and anticonvulsants (e.g., amitriptyline and gabapentin respectively) but they do not work for all patients and are often associated with side effects.
The goal of our project
The physiological mechanisms contributing to chronic neuropathic pain are complex and involve many molecular and cellular processes and pathways. Pain scientists across the globe are investing intense effort to identify neural, chemical, or gene biomarkers. This improves understanding of physiological mechanisms and helps in the design and development of better diagnostic tools and better drugs.
Our team’s immediate goal is to focus on substances detectable in the blood, such as proteins, to understand mechanisms of chronic neuropathic pain. Many studies have been carried out in non-human models, so in our study we took blood samples from humans to look at transcriptional changes associated with chronic neuropathic pain.
The complexity of the inflammasome pathway and differential gene expression found in our study
What did we do and what did we find?
We used comparative transcriptomic technologies, including Affymetrix microarray and qRT-PCR (quantitative Real-Time Polymerase Chain Reaction), to differentiate gene expression profiles of people who had chronic neuropathic pain and pain-free people. We found the genes MYC, STAT1, TLR4, CASP5 and WLS were expressed in people with chronic neuropathic pain and these genetic molecules (DNA) can serve as potential blood biomarkers. Interestingly, these genes are associated with inflammation, inferring that people with chronic neuropathic pain may have increased inflammation and a disturbed immune system.
We were able to identify merged networks of transcription regulators
What does this mean?
At present, screening of people with suspected chronic neuropathic pain is based on clinical history, physical assessment, and questionnaires capturing self-report of symptoms. Our study identified a variety of blood biomarkers that could be used as clinical risk predictors. These blood biomarkers could also be used to improve the precision of diagnoses and to inform the development of more effective and less harmful drugs to treat chronic neuropathic pain.
What next?
Our next step is to validate our findings in follow-up studies using larger samples of people so that we could rule out the possibility that depression, anxiety and medications influenced our findings. Our medium term goal is to evaluate the clinical utility of the prognostic biomarkers identified. Our long term goal is to use this information to inform predictors of clinical risk and the development of diagnostic tools and treatments, including drugs.
Professor Mark Johnson
Mark Johnson is Professor of Pain and Analgesia. He is an international expert on the science of pain and its management and the world leader on transcutaneous electrical nerve stimulation (TENS). He has published over 300 peer reviewed articles.
