Defining the link between peripheral neuronal activity and neuropathic pain
Lead Research Organisation:
University of Oxford
Department Name: Clinical Neurosciences
Abstract
Damage to peripheral nerves (neuropathy) can be devastating for those affected, especially when the damage to sensory nerves causes chronic pain (neuropathic pain). This pain is a major health problem linked to poorer quality of life, mental health distress, and greater healthcare use, even when compared to other forms of chronic pain e.g., arthritic pain. Neuropathic pain is common and will increase with an ageing population and rising rates of diseases associated with nerve damage, such as diabetes. The pain is underdiagnosed, and existing treatments are not that effective and have many side-effects. A key challenge is that there is little information to guide clinicians to match the right treatment to the right patient.
We need to understand more about how neuropathic pain develops to improve current treatments and find newer, more effective therapies. Previous research suggests that abnormal electrical activity within injured peripheral nerves is a key part of the problem. This abnormal activity is often the result of nerve damage from different causes, such as commonly used chemotherapy drugs and diabetes. Peripheral nerves are made up of different types of sensory nerves that respond to different stimuli. For example, there are sensory nerve subgroups that relay information about painful stimuli. These are called nociceptive fibres. They send signals to the brain when there is potential damage or actual harm to our tissues, like when we touch something hot or sharp.
My hypothesis is that the main reason many patients experience chronic neuropathic pain is because some types of nociceptive fibres are abnormally active. By directly measuring activity in these fibres, I can understand more about how they work and in what way they are abnormal in neuropathic pain states. The objectives of my fellowship are to determine how nociceptive fibre activity differs in patients with painful and painless neuropathy, and find the pattern of nerve activity that best fits with a patient's pain experience. I will also study how changes at the molecular level, from differences in pain genes, relate to nociceptive fibre dysfunction.
To test my hypothesis, I will use a neurophysiology tool called microneurography. This tool allows me to directly record and measure nerve fibre activity in nociceptive fibres by inserting a small needle into a peripheral nerve. Microneurography is the sole test, used by a few researchers, that can study single nerve signals in people. I will perform this test in patients with different types of neuropathy who have undergone a thorough clinical assessment. I will ask patients about their pain (how bad it is, where it hurts, what it feels like), and measure how they feel touch, temperature, and pain stimuli. I can construct a symptom and sensory profile specific to an individual from this clinical information. People with diabetic neuropathy, non-diabetic neuropathy and genetic pain disorders will take part.
My analysis will identify those individuals whose pain is caused by abnormal nociceptive fibre activity. This means that targeted pain treatments that reduce abnormal nerve activity can be used. I will develop a deeper understanding of the underlying physiology by matching clinical profiles and genetics to nerve activity. The new physiological knowledge that I discover will guide the development of novel therapies. This personalised approach avoids treatments that are unlikely to work and improves the chances of providing rapid and effective pain relief.
We need to understand more about how neuropathic pain develops to improve current treatments and find newer, more effective therapies. Previous research suggests that abnormal electrical activity within injured peripheral nerves is a key part of the problem. This abnormal activity is often the result of nerve damage from different causes, such as commonly used chemotherapy drugs and diabetes. Peripheral nerves are made up of different types of sensory nerves that respond to different stimuli. For example, there are sensory nerve subgroups that relay information about painful stimuli. These are called nociceptive fibres. They send signals to the brain when there is potential damage or actual harm to our tissues, like when we touch something hot or sharp.
My hypothesis is that the main reason many patients experience chronic neuropathic pain is because some types of nociceptive fibres are abnormally active. By directly measuring activity in these fibres, I can understand more about how they work and in what way they are abnormal in neuropathic pain states. The objectives of my fellowship are to determine how nociceptive fibre activity differs in patients with painful and painless neuropathy, and find the pattern of nerve activity that best fits with a patient's pain experience. I will also study how changes at the molecular level, from differences in pain genes, relate to nociceptive fibre dysfunction.
To test my hypothesis, I will use a neurophysiology tool called microneurography. This tool allows me to directly record and measure nerve fibre activity in nociceptive fibres by inserting a small needle into a peripheral nerve. Microneurography is the sole test, used by a few researchers, that can study single nerve signals in people. I will perform this test in patients with different types of neuropathy who have undergone a thorough clinical assessment. I will ask patients about their pain (how bad it is, where it hurts, what it feels like), and measure how they feel touch, temperature, and pain stimuli. I can construct a symptom and sensory profile specific to an individual from this clinical information. People with diabetic neuropathy, non-diabetic neuropathy and genetic pain disorders will take part.
My analysis will identify those individuals whose pain is caused by abnormal nociceptive fibre activity. This means that targeted pain treatments that reduce abnormal nerve activity can be used. I will develop a deeper understanding of the underlying physiology by matching clinical profiles and genetics to nerve activity. The new physiological knowledge that I discover will guide the development of novel therapies. This personalised approach avoids treatments that are unlikely to work and improves the chances of providing rapid and effective pain relief.
