What is peripheral neuropathy?
Peripheral neuropathy is damage to the nerves that communicate between the central nervous system (brain and spinal cord) and the rest of the body. Neuropathies in sensory nerves can lead to painful conditions (burning, tingling, numbness) and extreme sensitivity to temperature or pressure, whereas neuropathies in motor nerves can lead to problems controlling muscles and movement.
The limb extremities are typically the most severely affected areas. Damage to autonomic nerves can lead to problems with regulating involuntary functions of the body such as blood pressure, gut function and temperature regulation.
What causes it?Damage can occur to nerves as a result of diseases such as diabetes or viruses (like shingles or HIV), lifestyle or addiction issues such as alcoholism or obesity, after physical injuries or in cancer chemotherapy. However, there is still a lot that we don’t know about how neuropathies develop and in many patients the disease is considered ‘idiopathic’ (no known cause).
3-4% of people over the age of 55 suffer from peripheral neuropathy but it can also occur at younger ages. Some patients spontaneously recover but for others the neuropathy lasts for many years (or is indeed life-long). In patients that develop neuropathies, often little can be done to alleviate the symptoms. Conventional painkillers are ineffective and while there are some drugs for neuropathic pain the pain rarely disappears completely.
What are scientists trying to do about it?Scientists have linked many genes to peripheral neuropathies by studying families where several relatives show the same symptoms. Mechanisms are emerging that control the survival of axons (the long ‘wires’ that link nerve cells together) or that of myelin (the insulating material surrounding the axon).
Abnormal ion channels (proteins in the membranes of nerve cells controlling their excitability) can lead to excruciating pain upon light touch or small temperature changes. Blocking the function of these channels is a key goal in current drug development.
Another major area of peripheral neuropathy research is to understand what role defects in axonal transport play in the disease.
The loss of the extreme ends of the longest axons, particularly sensory nerve endings in the skin, is a common event in peripheral neuropathy and drugs such as Vincristine and Taxol that induce neuropathy disrupt transport processes delivering critically important molecules to maintain these nerve endings. If transport fails it is easy to see why the endings would degenerate. There is also considerable interest in the role of immune cells (white blood cells) in modifying and amplifying neuropathies through inflammation.
Axons in culture degenerate when exposed to Vincristine
Ongoing research in the Coleman lab
Our lab is trying to find a way of preventing pain from developing in cancer patients that receive chemotherapy. We discovered a protein that blocks axon degeneration after injury (Wallerian degeneration) and recently collaborated with a leading US fly group to identify another protein that is required for this degeneration.
These same changes block axon loss in some cell culture and mouse models of peripheral neuropathy. We are asking whether it also prevents pain symptoms and how widely it preserves axons in different models. Methods that we have developed for studying axonal transport in nerves also enable us to test whether changes in transport precede or follow axon degeneration and pain.
By identifying what changes first we can better target drug development against the initial step and block the whole process.
For more information on peripheral neuropathy see: